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Handbook of Genetic Counseling/Trisomy 13 - Advanced Maternal Age - Occupational Exposures

Trisomy 13 - Advanced Maternal Age - Occupational Exposures

Introduction

 * Discuss the reason for referral
 * AMA
 * Occupational exposures
 * Medication for migraines
 * Elicit prior knowledge
 * Trisomy 13
 * AMA
 * Exposures
 * Assess concerns and set goals for the session.
 * Provide overview of topics for counseling session
 * Pregnancy & family history
 * Address risks for the pregnancy
 * Introduce testing options

Client & Partner Information

 * Medical history
 * Any other chronic illnesses?
 * Migraines
 * Information about your husband:
 * Name, age, occupation?
 * Any exposures?
 * Any chronic illnesses?
 * Psychosocial assessment
 * Loss of prior pregnancy
 * Guilt about termination
 * Mourning for loss of fetus
 * Anxiety about future pregnancies
 * Self-blame
 * Did you name the fetus?
 * Do you have anything from the fetus such as ultrasound photos?
 * Support system
 * Friends and family in the area
 * Who did you tell about the condition?
 * What did you tell people about the loss?
 * How has it affected your marriage?
 * Future reproductive plans
 * Has it changed your future plans?
 * Would you again choose prenatal diagnosis?
 * How do the recurrence risk numbers feel to you?

Elicit History

 * Construct pedigree:
 * Abnormal # miscarriages, stillbirths, infant deaths?
 * Previous children with chromosome abnormality, Down syndrome, birth defects, mental retardation?
 * Consanguinity? Ethnicity? Other concerns/risk factors?

What is AMA?

 * Woman is age 35 & above at expected date of delivery.
 * As maternal age increases, risks of birth defects increase.
 * Women do not make new eggs like males make sperm.
 * They are born will all the eggs they will have in their life and these eggs mature with age.
 * There are procedures that can be done to assess the risk, but there are also risks associated with the procedures.
 * As women age, their risk of having a child with a chromosomal difference increases. Advanced maternal age begins at 35 years of age because a woman's risk of having a child with a chromosomal difference at 35 is equal to the risk of having a miscarriage via an amniocentesis (both risks are equal to 1 in 200).
 * The background risk for major birth defects for women of all ages is 3-5%.

Explain Chromosome Abnormalities

 * Explain genes and chromosomes
 * Show karyotypes
 * Show karyotype of fetus
 * Explain nondisjunction
 * Be prepared to explain meiosis in males versus females
 * Nondisjunction has not been found to be associated with environmental factors such as occupational exposures.
 * Show abnormal karyotypes (trisomy 13)
 * Give a general description of the clinical features and prognoses.
 * Trisomy 18 & 13 are most severe with most affected dying before the age of 1 year
 * Trisomy 21 is more mild; characteristic physical features and mild to moderate MR
 * Turner and Kleinfelter's syndromes are sex chromosome anomalies. Also usually mild.

What is Trisomy 13?

 * A chromosomal disorder resulting in a syndrome characterized by specific (midline) dysmorphic features and organ malformations
 * Pathogenesis:
 * A single defect during the first 3 weeks of development of the mesoderm
 * Leads to morphologic defects of the midface, eyes and forebrain
 * Natural History
 * Very poor prognosis
 * Median survival is 2.5 days
 * 82% die within the first month
 * 5% survive the first 6 months
 * Survivors show:
 * Severe mental defects
 * Seizures
 * Failure to thrive
 * Life-sustaining emergency surgery to a newborn with trisomy 13 may be inappropriate
 * Clinical Manifestations
 * Dysmorphic Features
 * Facial
 * Microcephaly
 * Wide sagittal sutures and fontanelles
 * Microphthalmia or anophthalmia
 * Cleft lip, cleft palate, or both
 * Abnormal or low-set ears often with deafness
 * Skeletal
 * Thin posterior or missing ribs
 * Simian crease
 * Flexion of the fingers
 * Camptodactyly
 * Polydactyly
 * Organ Malformations
 * Central Nervous System
 * Severe mental retardation
 * Holoprosencephaly (lack of the septation of the forebrain)
 * Apnea
 * Seizures
 * Cardiovascular
 * Coarctation, ASD, PDA, VSD, dextroposition
 * Gastrointestinal
 * Inguinal or umbilical hernia
 * Omphalocele
 * Genitourinary
 * Polycystic kidneys
 * Males: cryptorchidism, abnormal scrotum, ambiguous genitalia
 * Females: bicornuate uterus
 * Etiology
 * Trisomy 13
 * Occurs in 75% of cases
 * Due to meiotic nondisjunction
 * Translocation
 * 20% of cases
 * May be de novo or familial
 * Mosaicism
 * 5% of cases
 * Due to postzygotic mitotic nondisjunction
 * Usually less severe than full trisomy 13, but is variable
 * Incidence
 * 1/5000 - 1/12,000 live births
 * AMA is a risk factor
 * The prevalence of unbalanced chromosomal abnormality in the whole newborn population is about 1/250
 * Recurrence
 * Trisomy 13
 * There is not accurate empiric recurrence risk data for trisomy 13
 * It remains to be shown whether a true increased risk, taking maternal age into account, really exists
 * But, presumed that likelihood for recurrence is of "very low magnitude" for full trisomy 13 cases
 * Several studies have found no recurrences following approximately 100 pregnancies with trisomy 13
 * Prenatal diagnosis may be offered for reassurance
 * Maternal Serum Screening
 * CVS
 * Amniocentesis
 * Level II ultrasound

Quote Risks
Exposures in Pregnancy
 * Show charts to figure risk of chromosome abnormalities.
 * Give age-specific risks:
 * Age at EDD: ____________
 * Trisomy 13: 1 in ________
 * Down syndrome: 1 in _______ ( %)
 * Any CA: 1 in ________ ( %)
 * Types of studies done to assess safety in pregnancy
 * Animal studies
 * Case reports
 * Population studies
 * Explain what empirical data are
 * Occupational
 * Work with your employer to optimize safety conditions
 * Proper ventilation
 * Mask
 * Gloves
 * Lab coat
 * Cidex (Glutaraldehyde)
 * Chemical used in sterilization of medical instruments
 * Animal data
 * Was not teratogenic when administered in large doses to pregnant mice and rats
 * Human data
 * Questionnaire of women who sterilize instruments in hospitals found increase in miscarriage as compared to controls and compared to staff who were not involved in this activity during pregnancy
 * 16.7% in sterilizing staff, 10.6% in controls, 6.0% in sterilizing staff not exposed
 * BUT…when adjusted for age and other exposures, the significant increase in the miscarriage rate did not persist for glutaraldehyde (it did for ethylene oxide)
 * No information on birth defects was reported
 * Endozime
 * Bacteriostatic dual enzyme cleaner produced by Ruhof Corporation
 * No data on Reprotox
 * Migraine Medication
 * Must weigh the risk: benefit ratio
 * Asses the potential fetal risks
 * Determine the value of the medication to management of the mother's condition
 * Should speak to prescribing physician for recommendations
 * Imitrex (Sumatriptan)
 * A sulfonamide derivative used as a vasoconstrictor
 * Animal data
 * RATS
 * Did not impair fertility or reproductive success in rats at unspecified dose
 * No embryolethality at plasma levels 50x those in humans
 * No increase in congenital anomalies at unspecified subcu dose
 * Rabbits
 * Embryolethality occurred in pregnant rabbits treated at doses close to those producing maternal toxicity
 * This is 3x higher than dose attained in therapy for humans
 * Fetal
 * Human data
 * 15% of a single dose crosses the placenta as shown by in vitro studies
 * GlaxoSmithKline has a registry for exposure during pregnancy
 * 194 exposed pregnancies showed increase in adverse pregnancy outcome to be 3.1% which is the rate expected in the general population
 * There is a low level of excretion in breast milk, but this should not pose a risk because it is administered as a single dose at infrequent intervals
 * Zomig (Zolmitriptan)
 * Serotonin 1D agonist used as an antimigraine drug
 * Animal data
 * Administration to rats did not impair fertility
 * At plasma concentrations 5000x humans, there was an increase in embryolethality in rats
 * At 11x human dose in rabbits, embryolethality was also seen
 * Maternal toxicity occurred in these studies
 * Human data
 * There are no published references on human reproductive effects
 * Method of action is similar to Imitrex
 * Phenergan (Promethazine)
 * A phenothiazine with antihistaminic activity
 * Has been used as an antiemetic for morning sickness and an adjunct to narcotic analgesia during labor
 * Human data
 * Isolated reports of abnormalities have appeared, but have included other drugs and lacked proper control groups.
 * Better designed studies have shown no association with birth defects
 * For example the Collaborative Perinatal Project
 * Readily crosses the placenta when given near term
 * There are conflicting reports on neonatal respiratory depression after administration
 * There is no data on breast milk excretion
 * Demerol (Meperidine)
 * One of the most commonly used opioid analgesics
 * Animal Data
 * Increased incidence of exencephaly, cranioschisis, and other lesions in the hamster
 * Human Data
 * No association between use in the first trimester and abnormal morphologic development
 * Crosses the placenta and enters fetal circulation
 * Commonly used during parturition to sedate parturient and neonate (inadvertently)
 * Excreted into breast milk in small amounts; no adverse effects identified in nursing infants

Chorionic Villus Sampling (CVS)

 * What is it?
 * The chorionic villi are wisps of fetal tissue or finger-like projections that attach the pregnancy sac to the uterine wall
 * CVS is the technique in which this sample of placental tissue is obtained
 * It is unique because it is used to diagnose certain birth defects in the 1st trimester of pregnancy rather than later in the pregnancy like amniocentesis
 * It is usually performed at 10-12 weeks gestation
 * What can it NOT tell me?
 * CVS cannot detect neural tube defects such as spina bifida
 * For this reason, it may be useful to measure the amount of AFP in the maternal serum at 15-18 weeks gestation
 * Also, follow-up with US at 18-20 weeks is recommended
 * It cannot detect all birth defects or mental retardation
 * For example, congenital heart defects, cleft lip & palate cannot be seen.
 * Also the severity of the defect cannot be known from CVS
 * Exactly what does the procedure involve?
 * Show figures of CVS
 * Transcervical CVS:
 * Done at 10-12 weeks gestation
 * Gentle suction is applied to the tube to remove the villi
 * Discomfort is often minimal, perhaps similar to a pap smear
 * Transabdominal CVS:
 * Done at 10 weeks gestation or later
 * Using US to guide, a spinal needed is inserted through the abdomen into the uterine wall and into the placenta
 * The needle is moved back and forth several times through the placenta
 * Suction is used to remove the villi sample
 * CVS takes approximately 5-7 minutes (not including prep time)
 * The baby's heartbeat is monitored by US
 * The collected sample is examined under the microscope to confirm that fetal tissue and not maternal tissue was collected
 * If maternal cells were collected, the CVS will be repeated
 * The sample is sent to the lab
 * Results are available in approximately 10 days
 * What are the risks?
 * The background rate of pregnancy loss at 10-12 weeks is 2-3%
 * CVS increases the risk of miscarriage by 1/100 (1%) in women with a normal uterus
 * Reinforce that 99% of women will have a healthy baby
 * Some studies indicate an increased risk for limb defects when CVS is done before 10 weeks gestation
 * When performed at 10-12 weeks, most recent studies do not report an increased risk because limbs have already formed at this point
 * The risk is approximately 1/3000 (0.0003%)

Amniocentesis

 * What is it?
 * Procedure used to obtain a small sample of fluid from the fluid-filled sac that surrounds the fetus
 * Performed at 15 weeks gestation or later
 * 15-18 weeks is optimal because it leaves the patient with options
 * 22 weeks is probably the latest it can be done leaving the option of elective abortion
 * Amniotic fluid contains the fetus's urine as well as other cells from the skin, throat, and digestive tract
 * Fluid is studied in the lab for abnormalities
 * Exactly what does the procedure involve?
 * Show figure of amniocentesis.
 * You will lie down on your back with hands behind your head.
 * Your abdomen will be cleaned with alcohol or iodine.
 * A local anesthetic may be applied to your stomach.
 * Ultrasound will be used to locate the position of the baby and the placenta and to find a safe spot for the needle.
 * A long, thin needle will be inserted through the skin, into the uterus.
 * Then a small amount (about 1-2 tablespoons) of fluid is removed and the needle is withdrawn.
 * The procedure itself usually takes ~5 minutes.
 * The baby will quickly replace the fluid that is removed.
 * The baby's heartbeat will be monitored by ultrasound.
 * Fluid will be sent to the lab and results are available in 1-2 weeks.
 * What are the risks?
 * The risk of miscarriage is between 1/400 and 1/200.
 * This means that the added risk for pregnancy loss attributable to the procedure is 0.5% or less.
 * There is a risk of uterine infection but this is less than 1 in 1,000
 * There is a remote chance that birth defects can be caused by the amnio (0.1%).
 * There are special considerations for mothers who are Rh negative. They need to take RhoGam after the amnio procedure.

Offer Resources

 * March of Dimes information on prenatal diagnosis
 * www.modimes.org
 * 1-888-MODIMES

 * GlaxoSmithKline registry for Imitrex exposures during pregnancy
 * 1-800-336-2176

 * Reach out to Grieving Parents Support Group


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Handbook of Genetic Counseling/Trisomy 18

Trisomy 18

Contracting

 * What do you know about why you have been referred?
 * What do you know about the triple screen? What is your understanding of your test results?
 * What questions or concerns would you like to address today?
 * Overview of session:
 * Family and medical history
 * Explanation of maternal serum screening
 * Overview of results and what they mean
 * Explanation of genes and chromosomes
 * Information on Trisomy 18
 * Options for the future

Prenatal Intake

 * Important to obtain information on pregnancy and family history to help assess potential risks to pregnancy
 * Prenatal intake
 * How many times have you been pregnant? Any previous miscarriages or stillbirths?
 * History of infertility?
 * LMP beginning of November? EDC middle of August?
 * Any illness - infections, colds, fever, rashes?
 * Any bleeding?
 * Any exposures - X-rays (including dental), smoking, alcohol, recreational drugs, medications?
 * Any problems with pregnancy?
 * Personal background - occupation, religion, ethnicity, chronic illnesses for consultand and partner
 * Consanguinity?
 * Family history
 * Review information obtained previously
 * Any history of miscarriages, infertility, stillbirths, birth defects?
 * Other chronic illnesses, learning problems, health problems that we did not discuss?

Maternal serum screening

 * Background
 * Screening test
 * Not a diagnostic test
 * Used to identify women who are at increased risk for certain birth defects
 * These women then offered diagnostic testing
 * Negative or "normal" result does not mean that a child will not have a birth defect
 * Positive result is not a diagnosis of an abnormality
 * Can identify women at increased risk for Trisomy 21, Trisomy 18, or open neural tube defects
 * Blood test
 * Fetal and placental products can be detected in mother's blood serum during pregnancy
 * Can be offered from 14-22 weeks but most accurate at 16-18 weeks
 * Indirect measure of levels of three substances in mother's blood
 * Alpha-fetoprotein (AFP)
 * Produced by liver of fetus and excreted into amniotic fluid
 * Passes into mother's bloodstream and concentration rises gradually throughout pregnancy
 * Human chorionic gonadotropin (HCG)
 * Pregnancy hormone made by the placenta
 * Level peaks at 10 weeks and declines throughout pregnancy
 * Unconjugated estriol (uE3)
 * Hormone made by fetus and placenta
 * Level increases throughout pregnancy

Risk assessment

 * Laboratory calculates a woman's risks based on levels of three substance plus other factors
 * Gestational age
 * Marker levels change throughout pregnancy
 * Inaccurate dates are common reason for false positive
 * Gestational age can be confirmed by ultrasound
 * Maternal age
 * Multiple gestations
 * Maternal weight
 * Increased weight means increased blood volume
 * Markers will be diluted in serum and their concentration lower
 * Maternal race
 * Diabetic status
 * Insulin-dependent diabetics have increased risk for neural tube defects
 * Tend to have lower AFP levels, so use lower AFP cutoff
 * Your specific results:
 * Every pregnancy has 3-5% risk for congenital malformation
 * Background risk
 * Most of these problems cannot be detected prenatally
 * As a woman's age increases, her risk for certain birth defects increases
 * Risk figures for your pregnancy:
 * ONTD: ________
 * Down Syndrome: ________ compared to age associated risk _______
 * Trisomy 18: ________ compared to age associated risk _______
 * Screen positive for increased risk for Trisomy 18
 * Occurs when AFP, hCG, and uE3 levels are all lower than expected
 * Evaluation of screening performance
 * Up to 100 of every 1,000 women who take test will have abnormal result (up to 10%)
 * Only 3 of those 100 women will have a baby with a birth defect
 * Most abnormal test results indicate dates are wrong or another factor above has not been accurately accounted for
 * Important to remember that test cannot identify all birth defects
 * Abnormal result could be normal variation
 * Sometimes no explanation for abnormal results - increased risk for 3rd trimester complications
 * Test can detect:
 * 60% of Trisomy 18
 * 80% of ONTD
 * 60% Down Syndrome

Trisomy 18

 * Clinical picture
 * Can cause heart problems, kidney problems and other health issues
 * Usually fatal within first year of life
 * Children that survive have severe intellectual disability
 * Increased risk for pregnancy loss

Options for further testing

 * Ultrasound
 * Confirm gestational age or identify multiple fetuses to help interpret triple screen results
 * Can detect many major birth defects - rule out 95% of NTDs if visualization is not limited
 * Many fetuses with Trisomy 18 have certain "markers" that can be identified on ultrasound
 * Growth retardation
 * Single umbilical artery
 * Heart problems
 * Polyhydramnios
 * Can't diagnose chromosomal abnormalities
 * Amniocentesis
 * Performed after 15 weeks
 * Diagnostic test for some conditions
 * 99.7% accuracy for fetal chromosome analysis
 * Detects 96% of open neural tube defects by testing AFAFP
 * Cannot detect all birth defects or mental retardation
 * Risk of pregnancy loss due to procedure is 0.5%
 * Explain amniocentesis if interested
 * Insert needle into abdomen through uterus to take sample of amniotic fluid that contains cells from fetus used for karyotyping
 * Procedure:
 * Ultrasound to locate fetus and placenta
 * Abdomen cleaned with betadeine and local anesthetic (xylocaine) used to numb outer layer of skin
 * Physician inserts needle in abdomen through uterus under ultrasound guidance
 * Needle inserted 1-2 minutes
 * May feel some discomfort similar to menstrual cramp
 * Fluid is sent to lab and results ready in 1-2 weeks
 * Recommendations
 * No strenuous activity for 24 hours
 * Notify doctor if severe cramping, bleeding or leakage of fluid because there is very small risk of infection
 * Rh negative mothers should take RhoGAM

Potential Psychosocial Issues

 * Emphasize the importance of choice
 * Religious beliefs impact decisions about testing and termination
 * Anger, distrust because of family physicians advice
 * Anxiety, sadness, disbelief, fear concerning possibility of Trisomy 21
 * Provide reassurance when possible
 * Explain benefits of prenatal diagnosis to help prepare emotionally, mentally, and socially for birth of child with chromosome abnormality
 * False positive may cause unnecessary anxiety

Support Groups
Trisomy 18 Foundation at www.trisomy18.org

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/


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Corset/Tightlacing/Edwardian

In the Edwardian era, they have a great experience by Tightlacing.

1 2 3 4 5

title: Corset/Tightlacing/Edwardian


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User talk:64.92.165.10

Please don't spam, thanks.

title: User talk:64.92.165.10


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Abstract Algebra/Group tables

The Group of Order 2
Here is the group table for the only group of order 2

The Group of Order 3
Here is the group table for the only group of order 3

The Groups of Order 4
Here are the group tables for the only groups of order 4

The cyclic group of order 4
Notice that regardless of the way we notate this group, there is an element that generates the whole group. $$1 + 1 \to 2 \quad 1 + 2 \to 3 \quad 1 + 3 \to 0$$ $$ 2{}\times{} 2 \to 4 \quad 2 \times 4 \to 3 \quad 2 \times 3 \to 1 $$

The other group of order 4
For the following example, image the number 0 through 3 written in binary, then add the digits without any carrying. For example, 2 + 3  10 + 11    01     1 Since binary addition (without carry) is isomorphic to $$Z_2$$ we view this group as being two copies of $$Z_2$$ joined together. That's where the name comes from.

Other small groups
A list of groups of order 1 through 31 compiled by John Pedersen, Dept of Mathematics, University of South Florida

A list of groups names and some examples of group graphs from Wolfram, makers of Mathematica.

title: Abstract Algebra/Group tables


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Esperanto/Family

The Suffix -IN
In most languages there are separate words for items of different sexes. For example, in English a female bovine creature is a "cow" and a male bovine creature is a "bull" or "steer". This of course leads to much memorization of separate words, which is tedious and frustrating. Fortunately, Esperanto does away with this with two glorious letters: "in". Adding -in to the end of a noun's root transforms that word into a female version of the root. For example, the Esperanto word for a bovine creature ("bull", "steer" or "cow") is bovo. Adding -in to the root results in the word bovino, which translates to "cow". With only a few exceptions (those roots implicitly male or female), if a noun does not have the suffix -in, then the sex of the noun is unspecified. If one wants to emphasize that something is masculine, one may use the root vir- as a prefix, but this is rarely done.

The Prefix GE-
In Esperanto, the prefix ge- is used 1) to indicate the presence of both sexes in a group described by a male or female root (Esperanto does have a very few such words) or 2) to emphasize the presence of both sexes in a group. For example, Pedro has two friends: Esmerelda and Johano. When referring to them, Pedro could call them either amikoj or geamikoj, because amiko is simply a "friend". But his brother and sister must be his gefratoj, because frato is the word for "brother").

Examples words using the prefix ge- :
 * gelernejo - co-ed school
 * gepatroj - father(s) and mother(s)
 * gefratoj - brother(s) and sister(s)
 * genevoj - nephews(s) and niece(s)

Exercises
Translate the following sentences to/from Esperanto using what you know and the Vocabulary List below.
 * 1) Mi malamas la bebojn, ĉar ili venas el Usono.
 * 2) Our sister's name is Allison.
 * 3) Ŝia avino amas la kuzon de Mario.
 * 4) Is his aunt eating an apple or a banana?
 * 5) Saluton. Ĉu vi estas mia patrino?
 * 6) My uncles are thirsty.
 * 7) La  gepatroj estas koleraj, ĉar ilia filino estas malbela.
 * 8) The unhappy woman is dying.

Vocabulary/ 	Vortlisto Esperanto	   English bebo		baby infano		child/infant knabo		boy viro		man avo		grandfather patro		father onklo		uncle filo		son frato		brother kuzo		cousin feliĉa		happy kolera		angry bela		pretty soifi		to be thirsty, to thirst akvo		water morti		to die manĝi		to eat pomo		apple banano		banana aŭ		or

Answers

 * 1) I dislike the babies, because they come from the USA.
 * 2) La nomo de nia fratino estas Allison.
 * 3) Her grandmother loves Mario's cousin.
 * 4) Ĉu lia onklino manĝas pomon aŭ bananon?
 * 5) Hello. Are you my mother?
 * 6) Miaj onkloj soifas.
 * 7) The parents are angry, because their daughter is ugly.
 * 8) La malfeliĉa virino mortas.

What You Need To Know

 * The suffix -in comes after a noun's root and denotes a female.
 * The prefix ge- precedes a noun's root and denotes the presence of both sexes.

title: Esperanto/Family


title: User:Totophe64


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Handbook of Genetic Counseling/Tuberous Sclerosis

Tuberous Sclerosis

Contracting

 * What have you been told about why you were referred?
 * What questions or concerns would you like us to address today?

Disease characteristics and Etiology

 * Genetic disorder that causes tumors to form in such organs as brain, eyes, heart, kidneys, skin, and lungs
 * Autosomal dominant inheritance
 * 2/3 of affected individuals have new mutations
 * Recurrence risks
 * If one parent affected, each pregnancy has 50% chance of inheriting mutation
 * If neither parent affected, recurrence risk is 1-2% to account for possible germline mosaicism
 * High mutation rate estimated at 1/25,000
 * Penetrance 100%
 * Two genes have been implicated
 * TSC1
 * Locus 9q34
 * Gene product is hamartin
 * TSC2
 * Locus 16p13
 * Gene product is tuberin
 * Functions not fully understood but have tumor suppressor function
 * Form heterodimers so may act together
 * Regulate cell proliferation
 * Incidence is about 1 in 6,000 live births
 * 50,000 affected in United States
 * More than 100,000 affected worldwide
 * Affects both sexes, all races and ethnic groups

Clinical Features and Natural History

 * Extreme variability both among and within families involving any organ system
 * Skin (100%) - don't result in serious medical problems
 * Hypomelanotic macules (87-100%)
 * On any part of the body in any shape, including ash-leaf spots
 * Can be seen using a Wood's lamp
 * Facial angiofibromas (47-90%)
 * Typically appear across cheeks and nose
 * May be present at birth or 4-5 years of age
 * Shagreen patches (20-80%)
 * Thickened and elevated pebbly skin
 * Found on lower back or nape of neck
 * Fibrous facial plaques
 * Ungual fibromata (17-87%)
 * Small, wart-like tumors around or under fingernails and toenails
 * Usually do not appear until later in life
 * Central Nervous System
 * Lead to most morbidity and mortality
 * Subependymal glial nodules (90%)
 * Develop in walls of ventricles that contain cerebrospinal fluid
 * Calcification occurs in first few years of life so can be detected on CT
 * Not directly responsible for neurological problems
 * Cortical or subcortical tubers (70%)
 * Small areas on cortex that develop abnormally
 * May be cause of seizures
 * Cortical tuber count on MRI may predict severity of cerebral dysfunction (more than 7 in moderately to severely affected patients)
 * Subependymal giant cell astrocytomas (6-14%)
 * Usually do not occur in young children and chance for growth decreases after age 20
 * Can become large enough to block flow of fluid in ventricles causing nausea, vomiting, headaches, changes in appetite, behavior, and mood
 * Brain imaging should be done every 1-3 years
 * Seizures/epilepsy (60-90%)
 * Can cause infantile spasm/hypsarrhtyhmia syndrome
 * Early in life may consist of brief head nodding or staring
 * May occur less often or cease in older children and adults
 * EEG and documentation of what seizures are like is important
 * Developmental delay or mental retardation (50-65%)
 * Leading cause of premature death in TS is complications of severe mental retardation (32%)
 * Close related with age of child at onset, frequency, duration, and severity of seizures
 * Children may regress if loss of seizure control occurs
 * Psychiatric and behavioral problems
 * Aggression, sudden rage, hyperactivity, attention deficit, obsessive-compulsive behaviors, repetitive behaviors
 * Linked with autism
 * Occasionally may be diagnosed with schizophrenia, bipolar disorder, depression
 * Kidneys
 * Renal disease is second leading cause of early death (28%) but complications do not occur until 2nd or 3rd decade of life
 * 80% of children have renal lesion by age 11
 * At diagnosis children should have baseline ultrasound, MRI, or CT
 * Repeat every 1-3 years
 * Benign angiomyolipoma (70%)
 * Less than 1% can become malignant
 * Can cause life threatening bleeding
 * Epithelial cysts (20%)
 * Oncocytoma (<1%) and renal cell carcinoma (<1%)
 * Heart
 * Cardiac rhabdomyomas (47-67%)
 * Form in infancy and disappear with time
 * Benign tumors but can cause blockage and death if severe
 * Children should have EKG to check for these problems
 * Lung
 * Lymphangioleiomyomatosis of lung (1-6%)
 * Degenerative cystic disease of lung
 * May progress to respiratory failure or death
 * Primarily affects women between ages of 20 and 40 years
 * Eye (75%)
 * Hamartomas or achromic (hypopigmented regions)
 * Rarely cause vision loss or problems
 * Opthalmoscopy with pupils dilated may help diagnose TS in children
 * Liver, pancreas, and other organs may develop benign cysts later in life
 * Pits in both baby and adult teeth (90%)

Testing

 * Diagnosis based on clinical findings
 * Three classes
 * Definite TSC - 2 major features or 1 major plus 2 minor features
 * Probably TSC - 1 major feature plus 1 minor feature
 * Possible TSC - 1 major feature or 2 or more minor features
 * Many of findings are nonspecific and may be isolated or associated with other syndromes
 * Major features
 * Facial angiofibromas or forehead plaque
 * Non-traumatic ungual or periungual fibromas
 * Three or more hypomelanotic macules
 * Shagreen patch
 * Multiple retinal nodular hamartomas
 * Cortical tuber
 * Subependymal nodule
 * Subependymal giant cell astrocytoma
 * Cardiac rhabdomyoma
 * Lymphangiomyomatosis
 * Renal angiomyolipoma
 * Minor features
 * Multiple pits in dental enamel
 * Hamartomatous rectal polyps
 * Bone cysts
 * Cerebral white matter radial migration lines
 * Gingival fibromas
 * Nonrenal hamartoma
 * Retinal achromic patch
 * "Confetti" skin lesions
 * Multiple renal cysts
 * Molecular genetic testing
 * Available on a research basis for TSC1 and TSC2
 * Between 60-80% of families have identifiable mutation
 * Clinical testing is available for families who already have a mutation identified by research testing
 * Prenatal testing
 * DNA based testing possible for families at 50% risk with known gene mutation
 * High resolution ultrasound looking for tumors - unknown sensitivity

Surveillance/Management/Treatment

 * Patients undergo extensive initial evaluation to establish diagnosis
 * Patients require routine follow-up evaluations
 * Renal, cranial, chest CT or MRI
 * EEG for seizure management
 * Neurodevelopmental and behavioral evaluations
 * EKG if needed
 * Treat specific complications as needed

Psychosocial Issues

 * Guilt over new diagnosis, fear for child's future
 * Frustration over not being able to predict natural history
 * Burden of dealing with a child with serious health and behavioral problems
 * Frightening experience watching child have a seizure
 * Lifetime management

Resources

 * Tuberous Sclerosis Alliance
 * (800) 225-6872
 * www.tsalliance.org

 * Autism Society of America
 * (301) 657-0881
 * www.autism-society.org

 * Epilepsy Foundation of Greater Cincinnati
 * (513) 721-2905
 * www.epilepsyfoundation.org


text:
Wikijunior:Big Cats/Marbled cat

The marbled cat is the big cat that isn't big at all, only slightly larger than a domestic cat. Scientists place it in the same closely related group as the lion, tiger and leopard, the Subfamily Pantherinae, and even though it's much smaller than the clouded leopard it has the same long fangs and a very similar fur pattern. Scientific examination of their blood (blood serum analysis) suggests that they are similar in form to the forest ancestors of the big cats some ten million years ago. However, they may have also decreased in size more recently due to competition with other big cats.

Where do marbled cats live?
The marbled cat may be found in the forests of the Malay peninsula, Sumatra, Borneo and some neighboring small islands.

What do marbled cats look like?
Marbled cats look similar to clouded leopards but they are smaller, have shorter faces more like a domestic cat, and have a fuzzier tail. Its beautiful, striking coat is pale brown, with irregular slightly darker brown blotches sharply outlined in dark brown or black. Its long cylindrical tail is full from rump to tip and carries its body pattern.

What do marbled cats eat, and how do they catch their prey?
Marbled cats spend a great deal of time in the trees and it is likely that they catch much of their prey there, hunting birds, squirrels, rodents, frogs and reptiles. They have been seen hunting on the ground on the island of Borneo, and this may be a local habit. Not much is known about their habits because they are rare in the wild and there are no specimens currently kept in zoos.

Fun facts

 * Marbled cats make sounds similar to a domestic cat, but they purr rarely and their meow is somewhat like a twittering bird call.
 * The longest a marbled cat lived in captivity was 12 years.

For more information
Next Topic: Cheetahs
 * Wikipedia: Marbled cat

Wikijunior Großkatzen/ Marmorkatze

title: Wikijunior:Big Cats/Marbled cat


text:
Engineering Thermodynamics/Third Law

Third Law of Thermodynamics
The Third Law of Thermodynamics extends the definition of Entropy:

Entropy is zero only in a perfect crystal at absolute zero ( 0 kelvin [- 273.15 degree Celsius ]).

The Third Law of Thermodynamics can mathematically be expressed as

lim ST→0 = 0 (1)

where

S = entropy (J/K)

T = absolute temperature (K)

At a temperature of absolute zero there is no thermal energy or heat. At a temperature of zero Kelvin the atoms in a pure crystalline substance are aligned perfectly and do not move. There is no entropy of mixing since the substance is pure. By -VBM

title: Engineering Thermodynamics/Third Law


text:
Cookbook:Broccoli Burgers

Broccoli burgers are a handheld foodstuff similar to hamburgers though produced with eggs and vegetables in place of beef.

Ingredients

 * 2 standard eggs
 * 240 ml (1 cup) chopped broccoli
 * 120 ml (½ cup) chopped toasted almonds
 * 190 ml (¾ cup) chopped red onion
 * 120 ml (½ cup) seasoned dry bread crumbs
 * 80 ml (¼ cup) water
 * Salt to taste
 * Pepper, to taste
 * Toasted buns or bread
 * Mayonnaise
 * Lettuce

Preparation

 * 1) In a bowl, beat eggs.
 * 2) Stir in broccoli, almonds, onion, breadcrumbs and water.
 * 3) Add salt and pepper to taste.
 * 4) On an oiled 30x38 cm (12x15-inch) baking sheet, shape mixture into 4 patties, each 2 cm (¾ inch) thick.
 * 5) Bake in 190 °C (375 °F) oven, turning halfway through cooking, until each side is golden brown, about 25 minutes total.
 * 6) Serve on buns with mayonnaise and lettuce.

title: Cookbook:Broccoli Burgers


text:
Handbook of Genetic Counseling/Tuberous Sclerosis-2

Tuberous Sclerosis

What is Tuberous Sclerosis?

 * Referred to both as tuberous sclerosis (TS) and tuberous sclerosis complex (TSC). The term TSC is used in scientific literature to distinguish tuberous sclerosis from Tourette's syndrome.
 * Autosomal dominant disorder that causes benign tumors to form in many different organs, primarily in the brain, eyes, heart, kidney, skin and lungs
 * The disease affects some people severely, while others are so mildly affected that it often goes undiagnosed
 * The clinical symptoms of TSC vary greatly and may often not appear until later in life
 * Some people with TSC experience developmental delay, mental retardation and autism.
 * Many people with TSC are living independent, healthy lives
 * There are presently no cures and there is no way to predict how severely or mildly an individual may be affected by TSC
 * There can be complications in some organs such as the kidneys and brain that can lead to severe difficulties and even death if left untreated.
 * To reduce these dangers, people with TSC should be monitored throughout their life by their physician for potential complications.
 * Most people with TSC will live an average life span.

Who is affected?
The tumors are not cancerous!
 * Prevalence of TSC is unknown, but its incidence is estimated to be 1 in 6,000 live births. This means approximately 50,000 individuals in the United States and more than 1 million worldwide have TSC
 * It occurs in both sexes and in all races and ethnic groups
 * The tumors resulting from tuberous sclerosis are benign, but may still cause problems.
 * Tumors that grow in the brain can block the flow of cerebral spinal fluid in the spaces (ventricles) in the brain. This can lead to behavior changes, nausea, headaches or a number of other symptoms.
 * In the heart, the tumors are usually at their largest at birth, and then decrease in size as the individual gets older. These heart tumors, called cardiac rhabdomyomas, can cause problems at birth if they are blocking the flow of blood or causing severe arrhythmia problems.
 * The tumors in the eyes are not as common, but can present problems if they grow and block too much of the retina.
 * The tumors in the kidney (renal angiomyolipoma) can become so large they eventually take over all of the normal kidney function. In the past, the patient was left until they developed kidney failure. Today, doctors are more aggressive and remove individual tumors before they get too large and compromise healthy kidney tissue. Very rarely (less than 2 percent of) individuals with TSC develop malignant (cancerous) kidney tumors.

Inheritance and Recurrence Risks

 * Approximately 33 percent, or one-third, of people with TSC inherit it from a parent who also has TSC
 * A parent who is affected has a 50% or 1 in 2 chance of having an affected child
 * In the remaining 66 percent, or two-thirds of people with TSC, neither parent shows any symptoms or signs of TSC. It appears that one of the normal genes from either parent changes to the abnormal form, leading to a new (or sporadic) occurrence of TSC in the child
 * Normally, these parents do not have another child with TSC because the mutation was sporadic, not inherited
 * However, some families have more than one child with TS, even though neither parent showed symptoms or findings of TSC. This is due to germline mosaicism
 * Germline mosaicism is relatively rare, and this explanation does not apply to most families with a sporadically affected child.
 * However, due to germline mosaicism recurrence risk are quoted to be 1 to 3 percent
 * There is no simple way to determine whether an unaffected parent of a child with TSC has germline mosaicism.

Genes responsible

 * Two genes have been identified that can cause tuberous sclerosis.
 * Only one of the genes needs to be affected for tuberous sclerosis to be present.
 * The TSC1 gene is located on chromosome 9 and is called the hamartin gene.
 * The other gene, TSC2, is located on chromosome 16 and is called the tuberin gene.
 * The functions of hamartin and tuberin are not fully understood.
 * Hamartin and tuberin have been shown to form heterodimers, suggesting that these two proteins may act in concert to regulate cell proliferation
 * Both the TSC1 and TSC2 genes are believed to suppress tumor growth in the body.
 * When either of these genes is defective, tumors are not suppressed and tuberous sclerosis results.
 * The genes also play a role in the early fetal development of the brain and skin.
 * The genes (TSC1 and TSC2) are involved in approximately 70 percent of TSC diagnoses.
 * It is still unclear where the mutation lies in the remaining 30 percent of people tested.

Penetrance

 * The penetrance of TSC, after careful, detailed evaluation of each person known to carry a TS mutation, is now thought to be 100%.
 * Rare cases of seeming non-penetrance have been reported; however, molecular studies have resolved these cases, revealing two different sporadic TSC mutations in one family and the existence of germline mosaicism in others

Variable expressivity

 * The variability in expression exists because TSC is autosomal dominant at the level of the organism but recessive at the cellular level. (There is an element of chance involved)
 * Both the TSC1 and TSC2 genes have properties consistent with tumor suppressor genes functioning according to Knudson's "two hit"
 * The clinical variability occurs secondary to the random nature of the second "hit" in individuals carrying a germline mutation.

Genotype-Phenotype Correlations

 * The TSC1 and TSC2 phenotypes have been considered to be identical.
 * The phenotype is different in cases of a contiguous gene syndrome involving large gene deletions and rearrangements of both the TSC2 gene and the PKD1 gene on 16p13
 * One study found a greater risk of renal malignancy in patients with TSC2 and patients with TSC2 mutations have been found to have a higher frequency of mental
 * Genotype and phenotype correlation studies provide statistical support of a milder phenotype in patients with a TSC1 mutation.
 * A decreased proportion of individuals with TSC1 among sporadic cases of TSC has been reported. This might represent a true biologic phenomenon or decreased ascertainment of individuals with sporadic TSC1 because of a somewhat less severe phenotype.

Diagnosis and testing

 * The diagnosis of TSC is based on clinical findings (see clinical diagnosis in the category below)
 * Molecular testing is presently available on a research basis only
 * It is available on a clinical basis only to those families with a known TSC1 or TSC2 mutation identified through previous research studies.
 * Development of clinically available DNA analyses of the TSC1 and TSC2 genes has been hampered by the large size of the two genes, the large number of disease-causing mutations, and the high rate of somatic mosaicism (10-25%)

Prenatal Testing

 * DNA-based diagnostic testing is possible for pregnancies at 50% risk in a family with a known TSC1 or TSC2 gene mutation previously identified through a research study and confirmed in a clinical laboratory
 * DNA extracted from cells obtained from chorionic villus sampling (CVS) at about 10–12 weeks' gestation* or amniocentesis at 16–19 weeks' gestation can be analyzed for the known familial disease-causing mutations.
 * For other families, high-resolution ultrasound examination for tumors is available, but its sensitivity is unknown.
 * The risk for TSC is 50% in a fetus without a known prior increased risk for TSC, in which cardiac lesions consistent with rhabdomyoma are identified on ultrasound examination. Mutation analysis is currently not clinically available to further evaluate a fetus with this prenatal finding.

Clinical Diagnosis

 * The diagnostic criteria for tuberous sclerosis complex (TSC) were revised at the Tuberous Sclerosis Complex Consensus *Conference, July 1998
 * Definite TSC: Either two major features or one major feature plus two minor features
 * Probable TSC: One major feature plus one minor feature
 * Possible TSC: Either one major feature or two or more minor features

Major Features

 * Facial angiofibromas or forehead plaque
 * Non-traumatic ungual or periungual fibromas
 * Hypomelanotic macules (three or more)
 * Shagreen patch (connective tissue nevus)
 * Multiple retinal nodular hamartomas
 * Cortical tuber 1
 * Subependymal nodule
 * Subependymal giant cell astrocytoma
 * Cardiac rhabdomyoma, single or multiple
 * Lymphangiomyomatosis 2
 * Renal angiomyolipoma 2

Minor Features

 * Multiple randomly-distributed pits in dental enamel
 * Hamartomatous rectal polyps
 * Bone cysts
 * Cerebral white matter radial migration lines 1
 * Gingival fibromas
 * Nonrenal hamartoma
 * Retinal achromic patch
 * "Confetti" skin lesions
 * Multiple renal cysts
 * When cerebral cortical dysplasia and cerebral white matter migration tracts occur together, they are counted as one rather than two features of TSC.
 * When both lymphangiomyomatosis and renal angiomyolipomas are present, other features of tuberous sclerosis must be present before TSC is diagnosed.

Clinical Manifestations

 * We still cannot predict the severity of physical symptoms in a person with a new diagnosis of TSC.
 * A person can have TSC and have very few or mild symptoms, while a family member with TSC can have more severe or extensive

symptoms

 * In most individuals, the disease affects only some of these organs.
 * The severity of TSC can range from mild skin abnormalities to, in severe cases, mental retardation or renal failure.
 * Many TSC manifestations also develop later in life.
 * Most individuals who are mildly affected by TSC lead active and productive lives

Manifestations
Treatment
 * Echocardiogram can show rhabdomyomas, the most common primary cardiac tumor of tuberous sclerosis complex (TSC) in infancy and childhood.
 * The incidence of these tumors in TSC has been reported to vary from 47 percent to 67 percent.
 * Childhood tumor regression is the rule. In other words, in most cases, cardiac tumors are their largest at birth and may shrink or disappear as the individuals grow older.
 * A second peak in the incidence of these tumors may occur during puberty.
 * If cardiac outflow obstruction does not occur at birth, the patient is unlikely to have health problems from these tumors later.
 * Cardiac rhabdomyomas are more likely to be the cause of heart failure in a newborn infant or young child than in an adult with TSC.
 * Most rhabdomyomas of the heart are asymptomatic, but they should be treated by an experienced cardiologist if an arrhythmia or other cardiac problem is present.
 * Cardiac arrhythmias infrequently have developed in children just after starting carbamazepine (Tegretol), used for the treatment of epilepsy. Reports have also shown a significant increase in the size of cardiac rhabdomyomas in infants with TSC with infantile spasms who are treated with adrenocorticotropic hormone (ACTH). Therefore, echocardiograms and EKG baseline measurements should be obtained before initiating these treatments.

BRAIN INVOLVEMENT
Brain imaging should be done at the time of diagnosis to get a baseline image and then every 1 to 3 years afterwards. A brain scan can sometimes show growth of a tumor even before symptoms develop.
 * CNS tumors lead to the most morbidity and mortality in TSC
 * Brain and Neurologic Function: Several types of brain lesions are seen in individuals with TS; some people will have all the lesions, whereas others will have no brain involvement at all.
 * Cortical tubers (from which TSC is named)
 * Occur in 70% of patients
 * thought of as a "birth defect" on the brain
 * small areas in the cortex (the outer layer of the brain) that do not develop normally
 * It is thought that the presence of cortical tubers, which disrupts the normal "wiring" of the brain, is what causes seizures in individuals with TSC.
 * Subependymal nodules
 * occur in 90% of patients
 * develop near the walls of the cerebral ventricles (the cavities in the brain that contain cerebrospinal fluid)
 * Typically, these nodules accumulate calcium within the first few months or years of life.
 * Because of this calcification, they can be easily detected with a computed tomography (CT) scan.
 * The subependymal nodules are not directly responsible for neurological problems.
 * Subependymal giant cell astrocytomas (SEGAs).
 * occur in 6-15% of all patients
 * Typically, SEGAs do not occur in very young children, and the chance for their growth decreases after age 20.
 * Medicine can be given to treat it
 * If a giant cell astrocytoma grows large enough, it can block the flow of fluid inside the ventricles of the brain, can result in significant morbidity and mortality, the tumor will have to be removed and/or the ventricles shunted to relieve fluid buildup and pressure.
 * Symptoms include vomiting, nausea, and headaches as well as changes in appetite, behavior, and mood.
 * These symptoms may or may not signal growth of a tumor, but they do signify that there may be a problem and that the child should be seen by a physician.

EPILEPSY/SEIZURE DISORDERS

 * Seizures occur in 60 percent to 90 percent of individuals diagnosed with TSC
 * They are often the first symptom of TSC.
 * Early in life, the seizures may consist only of brief head nodding or staring, or they may be more generalized, with spasms of the limbs and flexion and extension of the head and trunk.
 * In older children and young adults, the seizures sometimes occur less often or cease.
 * If seizures are suspected, an electroencephalogram (EEG) is usually conducted.
 * Seizure control in a child with TSC is important.
 * There appears to be a direct relationship among the age of the child at the onset of seizures; their frequency, duration, and severity; and the degree of mental handicap.
 * Antiepileptic drugs (AEDs), properly administered, may control the seizures completely, although in some people the seizures return or cannot be controlled.
 * Some children with TSC have "infantile spasms." During this type of seizure, the child brings his legs up to his chest in a repeated motion.
 * Infantile spasms can sometimes be eliminated by the use of adrenocorticotropic hormone (ACTH), a hormone from the pituitary gland that stimulates the adrenal glands to produce cortisone. This medication is not used for long periods of time because of adverse side effects.
 * Valproic acid (Depakene) has also been used to treat infantile spasms.

COGNITIVE, PSYCHIATRIC AND BEHAVIORAL INVOLVEMENT

 * The behavior of a child with TS can often be the most difficult and trying problem for parents and family.
 * Aggression, sudden rage, hyperactivity, attention deficit, acting out, obsessive-compulsive behavior, repetitive behaviors, staying in their "own world," being nonverbal even at an age when most children are speaking, and other autistic behaviors have all occurred in children with TSC.
 * At least 50% of patients have developmental delay or mental retardation
 * Some children with TSC, usually those who have a mental disability, are also diagnosed with autism.
 * There appears to be a connection between TSC and autism that is not understood, and active research is exploring this link
 * Occasionally, individuals with TSC are also diagnosed with schizophrenia, bipolar disease (manic depression), depression, or other psychiatric disorders.

Manifestations

 * lymphangioleiomyomatosis (LAM) - pulmonary cystic disease
 * estimated to occur in 1-6% of cases
 * primarily affects women between the ages of 20 and 40 years
 * The first symptoms of lung involvement in an individual with TSC may be shortness of breath after mild exercise, spontaneous pneumothorax, or coughing.
 * Progression to pulmonary failure may develop, but not usually until the third or fourth decade of life, if at all.
 * Pulmonary involvement in TSC can be severe, and some individuals will require lung transplantation.

Diagnostic screening and follow-up

 * Recent studies have shown that many women with TSC have minor, asymptomatic lung involvement.
 * The Consensus Conference Panel on Lung Involvement recommended that female patients should have a chest CT scan (not an x-ray) sometime before age 18 or at the time of diagnosis for women older than 18.
 * A CT scan of the lung is superior to an X-ray because the early signs of lung involvement may easily be missed on an X-ray.
 * If pulmonary involvement is noted, the individual should be monitored closely and should have repeated chest CT scans as needed.

Treatment

 * Pulmonary involvement in TSC can be severe, even fatal.
 * Recently, tamoxifen and progesterone have been used to treat pulmonary TSC with encouraging results.
 * Any individual with TSC with lung involvement should see a pulmonologist who is knowledgeable about LAM.
 * National Institutes of Health is also conducting clinical research of LAM
 * Call the Tuberous Sclerosis Alliance or the LAM Foundation for more information.

KIDNEY INVOLVEMENT

 * The second leading cause of early death (27.5%) in patients with TSC is renal disease
 * In a recent study, an estimated 80% of children with TSC were found to have an identifiable renal lesion by the mean age of 10.5 years

Manifestations

 * TSC can present itself as five different lesions in the kidneys:
 * benign angiomyolipomas-(occurring in 70 percent to 80 percent of adults and older children with TSC)
 * Renal angiomyolipomas-made up of vascular tissue (angio), smooth muscle (myo), and fat (lipoma)
 * They are benign hamartomas.
 * These hamartomas are well circumscribed groups of cells that multiply excessively, growing as benign tumors that may or may not cause symptoms.
 * The prevalence of TSC-related renal angiomyolipomas increases with age, and in adults bilateral tumors or multiple tumors in one kidney are common.
 * Angiomyolipomas begin in childhood in many individuals with TSC, but they usually grow very slowly and may not be problematic until young adulthood.
 * Individuals with TSC should have their kidneys imaged at the time of diagnosis and then regularly throughout their lives.
 * Accurate noninvasive ultrasound, CT, or MRI diagnosis of these benign lesions is highly dependent on their fat content
 * It can sometimes be difficult to tell the difference between a small or low-fat-content angiomyolipoma and a malignant tumor.
 * When tumors become larger than 4 cm, bleeding of the angiomyolipoma, the primary complication of this lesion, increases in frequency.
 * Pain may also become a significant problem with angiomyolipomas.
 * Cysts (occurring in 20% of patients)
 * TSC renal cysts are commonly multiple and bilateral.
 * They are the second most frequently occurring kidney manifestation of TSC.
 * Single or multiple renal cysts occur less often in individuals with TSC than do angiomyolipomas, but they may appear earlier.
 * Some cysts may collapse and disappear.
 * One important research finding was the discovery of the TSC2 gene in close proximity to the gene for polycystic kidney disease (PKD1) on chromosome 16.
 * A small group of individuals with TS have a large segment of chromosome 16 deleted, which means that both the TSC2 and PKD1 genes are removed.
 * malignant angiomyolipoma (<1%)
 * Malignant angiomyolipomas should be removed as soon as possible after their detection.
 * oncocytoma (benign adenomatous hamartoma) (<1%)
 * Oncocytomas are benign tumors only occasionally seen in individuals with TSC.
 * renal cell carcinoma (<1%)
 * rarely seen in individuals with TSC, but when these tumors are present, they often are multi-centric and bilateral.
 * These tumors should also be removed as soon as possible after their detection to prevent metastasis.

Diagnostic screening and follow-up
Treatment
 * Both renal angiomyolipomas and cysts are often asymptomatic and may not require treatment
 * Both should be followed closely with imaging every 1 to 2 years because aggressive treatment can preserve kidney function with minimal trauma to the individual or the kidney.
 * If the tumors are allowed to grow, they may lead to obstructive uropathy or displacement of much of the normal kidney tissue.
 * There is also a significant risk of hemorrhage if the angiomyolipomas or cysts grow larger than 4 cm.
 * Hematuria, back or abdominal pain, or internal hemorrhage may be the initial signs of kidney problems.
 * The renal lesions that appear in many individuals with TSC may remain stable and require no specific treatment.
 * Renal tumors must sometimes be removed, however, if they grow rapidly, if there is an indication that they may be malignant (i.e., a solid tumor with little or no fat content), or to alleviate obstruction.
 * With more frequent imaging of the kidneys and good clinical care, an individual with TSC should not have to lose an entire kidney or experience hemorrhaging from an angiomyolipoma.
 * Early and aggressive treatment is much better for most individuals with TSC
 * Unfortunately, some individuals with TSC who also have polycystic kidney disease will also have problems maintaining normal blood pressure levels.
 * Their blood pressure usually can be controlled with medication early in the disease process; however, dialysis, and sometimes even renal transplantations, may eventually be necessary.
 * Renal transplantation has been performed successfully in individuals with TSC; there does not appear to be a recurrence of angiomyolipomas in transplanted kidneys

SKIN INVOLVEMENT

 * The skin is affected in virtually 100% of patients.
 * Individuals with tuberous sclerosis complex (TSC) often see the disease manifested on the face, body and nails.
 * In some cases, skin growths can become obtrusive but in most cases, the growths themselves are harmless.
 * However manifestations such as facial angiofibromas can have a social impact and treatments are available.

Manifestations

 * hypomelanotic macule
 * (87-100% of patients)
 * patches of skin lighter than the surrounding skin (can be any size or shape or may be the classic "ash-leaf" shape)
 * shagreen patch-(20-80%)a patch of skin that is tough and dimpled like an orange peel
 * periungual or subungual fibromas-(17-87%) fibrous growths that appear around the fingernails and toenails
 * facial angiofibromas-(47-90%)
 * cause the most disfigurement
 * benign tumors of the face
 * may not be present at birth; do not usually appear until between the ages of 3 and 5 at the earliest
 * Fibrous plaquessometimes appear on the forehead of individuals with TSC. There may also be fibrous, hairless scalp plaques surrounded by thin, white tufts of hair.
 * Occasionally an individual with TSC coincidentally will have café au lait spots (areas of skin darker than the surrounding skin, but lighter and usually larger than a mole)
 * these skin lesions are not diagnostic of TSC.
 * A child with three or more or an adult with five or more café au lait spots may be diagnosed with neurofibromatosis

Diagnostic screening and follow-up treatment

 * At the initial testing, the physician uses a Wood's lamp (an ultraviolet light) to better visualize the hypomelanotic macules-white patches on the skin that often are difficult to see, especially on infants and people with very pale skin.
 * The entire body should be examined.
 * The skin should be carefully examined for the other skin manifestations of TSC as well.

Manifestations
plaque-like hamartoma.
 * The appearance of retinal lesions varies from the classic mulberry lesions adjacent to the optic disk to the more common
 * Retinal hamartomas
 * occasionally noted in individuals without other manifestations of TS and in individuals with other disorders.
 * although they are suggestive of TSC, single lesions are not diagnostic of TSC.
 * The frequency of retinal hamartomas in individuals with TSC has varied in reports from almost negligible to 87 percent of individuals (a difference probably reflecting the technique used and the expertise of the examiner)
 * Although less common than the retinal hamartoma, a defect in the pigment of the iris has also been observed in some individuals with TSC.
 * In addition, white depigmented patches, reminiscent of the hypopigmented macules on the skin, have also been observed on the retina of some individuals with TSC.

Diagnostic testing and follow-up

 * Retinal lesions may be difficult to identify without pupillary dilation and indirect ophthalmoscopy, particularly difficult to examine in uncooperative children.
 * Most retinal hamartomas remain dormant, although occasionally individuals with TSC have visual impairment resulting from a large hamartoma in the macular region.
 * Instances of visual loss following retinal detachment, vitreous hemorrhage, or hamartoma enlargement are rare.

Treatment

 * For the most part, treatment of the retinal lesions and repeated ophthalmologic examinations are unnecessary.
 * Normal eye care should be maintained.

OTHER ORGAN INVOLVEMENT

 * Cysts and tumors similar to those observed in the kidney sometimes appear in the liver, lung, pancreas, and other organs. These lesions are not usually seen until later in life and are rarely symptomatic.
 * Bone cysts can also develop but usually do not cause problems until later in life.
 * In addition, pits have been noted in both baby and adult teeth in over 90 percent of individuals with tuberous sclerosis complex (TSC), but their significance is not known.
 * Rectal polyps have also been reported but do not appear to cause problems.

Initial Evaluation

 * It is recommended that individuals suspected of having TSC have the following initial evaluation to establish the diagnosis and to identify potential complications for timely treatment. The evaluation and management plan described below was developed by the Clinical Issues Panel, Panel 1, at the Tuberous Sclerosis Consensus Conference in July, 1998
 * Medical history, especially for features of TSC
 * Family history, especially for features of TSC
 * Physical examination with use of a Woods lamp (ultraviolet light) in a darkened room and special attention to dermatologic findings
 * Cranial CT/MRI
 * Renal ultrasonography
 * Ophthalmologic examination
 * Electrocardiography and echocardiography, if cardiac symptoms indicate
 * Electroencephalography, if seizures are present
 * Neurodevelopmental and behavioral evaluation
 * Chest CT for adult females

KEY

 * MRI is magnetic resonance screening; EEG is electroencephalogram; ECG is electrocardiogram; ECHO is echocardiogram; and CT is computed tomography.
 * + indicates screening recommended; - indicates screening not recommended
 * b With negative physical examination results, CT is recommended.
 * c Every 1 to 3 years.
 * d Probably less frequently than in children.
 * e As clinically indicated.
 * f Unless seizures are suspected, this is generally not useful for diagnosis.
 * g Unless needed for diagnosis.
 * h Every 6 months to 1 year until involution or size stabilization occurs.
 * i Ultrasound is generally recommended due to cost, although local imaging expertise may vary.
 * j Every 3 years until adolescence.
 * k Generally for children only.
 * l Recommended for children at the time of beginning first grade.
 * m For women at age 18.

Differential Diagnosis

 * Many of the features of TSC are nonspecific and can be seen as isolated findings or as a feature of another disease.
 * Depigmented patches have been reported to occur in up to 8 per 1000 newborns and in most cases have no medical significance.
 * Other diseases that have hypopigmented macules as part of the phenotype include
 * Vitiligo
 * nevus depigmentus
 * nevus anemicus
 * piebaldism
 * Vogt-Koyanagi-Harada syndrome
 * acne vulgaris, acne rosacea, or multiple trichoepithelioma can be mistaken for angiofibromas
 * shagreen patchrd are rare but can be seen in families or sporadically
 * Ungual fibromas can result from trauma but generally these are single lesions and their presence can be explained
 * Renal cysts are seen in 1-2% of population, but not usually in people under 30 years of age
 * Renal angiomyolipomas (AMLs) are rare tumors sometimes observed in individuals with no other medical problems. They show loss of heterozygosity TSC2.
 * 50% of Infants with cardiac rhabdomyomas are affected with TSC and the others are an isolated finding

Psychosocial Issues
o Most parents reported that their concerns were initially ignored o It took a median of 3 physicians before a diagnosis established in children with infantile spasms o Infantile seizures were not diagnosed correctly in 40% of the TS patients
 * Denial is a common reaction when a parent first learns of the diagnosis
 * They may feel overwhelmed, sad, fearful, angry, guilty
 * A survey of families associated with a TS support group in North Carolina
 * The disfigurement caused by the tumors can lead to social isolation and self-esteem issues
 * Stress and anxiety may persist due to health concerns

IDENTIFIED RESOURCES

 * Tuberous Sclerosis Alliance
 * 801 Roeder Road, Suite 750
 * Silver Spring, MD 20910
 * Phone: 800-225-6872; 301-562-9890
 * Fax: 301-562-9870
 * Email: ntsa@ntsa.org
 * www.tsalliance.org

 * NCBI Genes and Disease Web page
 * www.ncbi.nlm.nih.gov/disease/TSC.html

 * American Epilepsy Society
 * 342 North Main Street
 * West Hartford, CT 06117-2507
 * Phone: 860-586-7505
 * Fax: 860-586-7550
 * Email: info@aesnet.org
 * www.aesnet.org

 * Epilepsy Foundation of America
 * 4351 Garden City Drive
 * Landover, MD 20785
 * Phone: 301-459-3700; 800-EFA-1000
 * Fax: 301-577-4941
 * Email: webmaster@efa.org
 * www.efa.org

 * National Tuberous sclerosis Association
 * 8181 Professional Place, Suite 110
 * Landover, Maryland
 * 20785-2226
 * Tel -1800-225-6872
 * Email - ntsa@ntsa.org


text:
Handbook of Genetic Counseling/Turner Syndrome

Turner Syndrome

(Ullrich-Turner syndrome or Bonnevie-Ullrich-Turner syndrome)

Incidence

 * 1/2,500 - 1/5,000 liveborn females based on screening newborn pop.
 * perhaps 1% -2% all conceptions (occurs more often in preg. losses)
 * 95-99% miscarried most in 1st trimester
 * usually sporadic not associated with AMA
 * recurrence risk not increased for subsequent pregnancies

Prognosis

 * Prematurity more common in preg. with Turner
 * mean birth weight in full term between 25-50 %ile
 * mean length in 5%ile of normal female
 * by 18 mths most growing at or below 3%ile height
 * Most consider standard of care to treat with growth hormone (although not deficient) differences in height appear to be a few centimeters (some studies not confirm this)
 * most adults adjust to petite stature
 * Feeding problems common including freq. spitting, vomiting and difficulty sucking and latching on also can have gastroesophageal reflux and failure to thrive
 * Obesity can be problem in later childhood and adult (excess calorie intake decrease expenditure -- short girls less likely to physical activity not intrinsic metabolic abnormality

Treatment/screening

 * encourage physical activity
 * educate about nutrition
 * hormone replacement (family informed decision appears safe, but not much long-term data) begin at age 4
 * treat age appropriately not according to height
 * annual echo recommended
 * begin at years thyroid function screening every other year and yearly in adults
 * periodic urinalysis for glucose
 * ovarian hormone therapy initiated at about 14 years
 * eye exam in infancy and refer at any time if concerns

Life expectancy

 * one population 156 with Turner's found 5 fold increase (15 deaths) in death rate over expected and 3 fold when congenital heart disease excluded
 * series of 500 liveborn patients, 25 died 10 due to complications of CHD.
 * Among 215 adults 5 cardiac, 2 accident, 1 malignant hyperthermia, 1 AML, 1 acute febrile syndrome, 3 old age

Physical Features

 * short stature
 * high arched palate
 * prominent ears
 * webbing of neck
 * low posterior hairline:trident configuration
 * increased carrying angle of arm
 * puffy hands and feet (lymphedema) may take months to several years to go away
 * hypoplastic nail beds
 * multiple pigmented nevi

Possible Health Concerns

 * frank gastroesophageal reflux and failure to thrive also noted
 * ear infections and sensorineural hearing loss is seen
 * structural renal malformations found in ~40%: horseshoe kidney, duplication of ureters
 * minority can have recurrent UTI and hydronephrosis
 * cardiac anomalies: estimated 17-45% coarctation of aorta, bicuspid aortic valve, hypoplastic left heart, VSD (risk of aortic dissection may be increased)
 * hypertension and mitral valve prolapse
 * streak gonads w/ absent oocytes, normal uterus but may be small
 * 90% require estrogen to initiate puberty and est. progest. to maintain menses
 * lack pubertal development and no onset of menses (97%)
 * infertility 99%
 * frequent dislocation of patella and knee pain common
 * Increased incidence of autoimmiune disorders
 * hypothyroidism common 15-30% of adults

Development and Behavior

 * Usually have ave IQ within normal range shifted to left 10-12 points, compared to sibs
 * ~10% have significant delays need special education and may need ongoing assistance in adult life with job or living
 * discrepancy between verbal and performance IQ (verbal usually normal performance 10-12 points lower)
 * visual spatial weaknesses: copy designs, memory visual patterns, left-right directions, math
 * some studies show increased anxiety in younger girls, social withdrawal and depression in older girls
 * Some girls may have hyperactivity, immature behavior, difficulty focussing
 * later to date, leave home, and marry than age-matched cohorts
 * surveys show: most well educated, most function in employment BUT problems with methodology

Reproductive options

 * IVF with donor oocytes (has been successful) expensive not always covered by insurance > 230 pregnancies in 93 women (1995) risk of SA (if fertile higher risk of trisomy 21)
 * adoption

Possible psychosocial concerns

 * difficulty having a child with multiple medical problems
 * balancing the care of two children can be difficult anyway without added concerns
 * disappointment at prospect of child not being able to have biological children

Resources

 * http://www.turnersyndrome.org/ (website for the Turner's Syndrome Society of the U.S.)


text:
Cookbook:Stuffed Tomatoes

Ingredients

 * 1 large, ripe tomato
 * 1 large, or 2 small culinary mushrooms
 * 1 sliced onion slab, or coin, about ¼ inch (0.5 cm) thick
 * 4 fresh basil leaves or 2 tsp dried basil
 * 2 tbsp fresh parsley or 2 tsp dried parsley flakes
 * 1 tsp dill weed
 * 2 dashes black pepper
 * 1 dash garlic powder
 * 1 dash salt
 * 5 drops cooking oil

Procedure

 * 1) On the head of a fresh tomato, cut two concentric rings, one near the stem, the other near the slope of the tomato's shoulder.
 * 2) Remove this ring to expose the juicy seed compartments.
 * 3) Slice the mushrooms into small, flat slabs, and cut the onion coin in quarters, like a pie or quiche. Separate the layers.
 * 4) In the open ring sprinkle the dried spices.
 * 5) Force the mushrooms and small arcs of onion through the spices and into the seed compartments, pushing the basil/dill/parsley/etc in with them. Stuff in as many as possible without forcing out tomato pulp. If using fresh basil leaves, fold them over the slices of mushrooms and push them in together.
 * 6) Drizzle five or so drops of cooking oil in a spot on a baking sheet or small roasting flat. Rub in a small circle with a diameter equal to the foot, or butt of the tomato.
 * 7) Place the tomato on the oil and the pan into an oven preheated to 350°F (180°C).
 * 8) Roast for 15–20 minutes.

Notes, tips, and variations

 * The onion slice will produce enough pieces for at least 4 stuffed tomatoes. If making several, 1 should be all you need.

title: Cookbook:Stuffed Tomatoes


text:
Islam Way of Life/Limits

The influence of The Assent is not limited to personal values and rituals, but in public as well. Some law makers call the influence of The Assent in public policy as "Islamic law", some just call it "law". Even when it is called Islamic Law, the exact legislation may differ from country to country. In Malaysia, it is even different from state to state.

Such difference is expected, since each country or state has different goals and different history. Koran only regulates upper and lower Theoretical Legal Limits as mentioned in Koran 4:13-14. This allows every nation to pick any point or range within The Theoretical Legal Limits to be their legislation. As an example of lowering the maximum limit, Brunei Darussalam abolished the death penalty. Another, the Queen of Jordan does not cover her hair. Its neighbor, Saudi Arabia has raised the minimum limit, so it is a crime not cover a female hair. So, please maintain that this chapter will only cover the theoretical legal limits and not the various actual local legislation of the same law.

Koranic concept of public policy is mentioned in Koran 3:104. In this book, the policy of acceptable and unacceptable is called legislation. In Koran 42:38, mutual consultation is the best way to decide the legislation and leadership between people but without violating the Koranic Legal Limits. Therefore the Koranic concept of consultation is somehow comparable to the concept of Democracy. At the same time, Koranic concept of Legal Limits is somehow comparable to the concept of Human Rights. These legal limits are designed to guarantee not only freedom but also fairness (justice).

Scholars differs on the role of Islam in the public policy. Scholars like Ayman Dhawahiri in Afghanistan/Pakistan does not accept any other source of law outside Koran and Hadith. Scholars like Muhammad Shahrour from Syria takes Koran as Legal Limits and Hadith as example, while allowing their implementation as wide as allowed by the Legal Limits imposed by God. Scholars like Yusuf Qaradhawi in Qatar, also the head of the European Council for Fatwa and Research, takes the middle road. However, they all are agreed on the importance of The Assenter's charter and The Believer's charter in the private life.

Civil Law Limits
NOTE:
 * 1) Bible are referred for comparison only.
 * 2) These are limits. The actual law may differs significantly but does not violates the limits, for example actual dress-code law may be much more restricted than God's limits.
 * 3) Some of these limits are restricted only to a specialized group. But legislation can be made to extend it, for example limits only for prophets wives can be extended to all believing women, or even to all women.

Human Rights

 * Where is the right of equality? 4:58, 5:8, 49:12
 * Where is the right of justice? 4:148, 49:12, 53:38, 2:282, 42:40
 * Where is the right of property? 24:27-28, 2:188, 24:29
 * Where is the right of privacy? 49:12
 * Why God's law is unchangeable? 30:30, 35:43, 33:62, 48:23

Open Government

 * Where is open government? 58:9-10, 58:11, 2:188, 49:6
 * How to decide public policies? 42:36-38
 * Where is election, referendum and parliaments? 42:36-38
 * Where is free press, demonstration and political participation? 58:11
 * How to built representation? 5:12, 37-147-148, 22:40
 * Can we force our view on others? 2:256
 * Should ruler listen his to people or become a dictator? 9:61, 3:159
 * Should we seek win-win solution? 24:62
 * Should we trust democratic decision? 24:63

Corruption

 * Can we cooperate on crime and aggression? 5:2
 * Should we obey ruler unconditionally? 60:12
 * Can we do money politic & bribery? 2:188
 * Can we annoy others? 31:19
 * Can we neglect our trust? 8:27, 3:161

Oppression

 * Can we kill apostates? 4:137, 2:256, 10:99, 88:21-22, also Bible Lev 24:16, Deut 13:5, Deut 13:6–10
 * Can we represent God on earth? 6:150-151
 * Can use religion for financial profit? 2:41, 2:79, 2:174, 5:44, 9:9, and 9:34, also Bible Mal 3:8, Ps 110, John 8:39, Lev 27:30-33, Lev 27:3-7, Lev 27:14-17, Lev 27:26-28
 * How to build a nation? 13:11, 6:123
 * How to avoid oppression? 4:97

Military Service

 * Should we serve in military service? 2:216, 8:65
 * What is the reasonable number of army to win a war? 8:65, 3:124-125
 * Should build military power? 8:60

Defensive War

 * Are we allowed to make peace to foreign invader? 2:190-193
 * What to do with foreign soldier? 2:190-191
 * What to do with mercenaries? 5:45
 * What to do with traitor? 5:33-34
 * What to do with contractor, supplier, financer etc.? 8:42

Aggressive War

 * Can we do secret war? 2:204-205
 * Can we conquest others? 8:19
 * To help the oppressed, emigrate them or change the ruler? 4:75, 8:72
 * How to keep peace in foreign country? 9:12, 4:94, 49:9-10
 * When to stop war? 8:61-62
 * What to do with deserter? 8:15-16
 * What to do with prisoner? 8:67, 8:70, 47:4
 * What to do with spoils of war? 8:1

War Strategy

 * What to do to prepare battle? 8:26, 8:60,34:11, 21:80, 27:22, 9:38, 9:41
 * What to do in battle? 8:42, 61:4, 47:4, 8:46, 3:121, 8:15-16, 8:45
 * What to do with traitor? 8:58
 * What to do for loses? 8:65, 3:140, 3:165, 3:144, 3:157-158, 3:169-171, 3:173, 33:22

See ../Glossary for more about the terminology being used in this chapter.

Talk Back
Do you know two Moslem countries or provinces that has differing law of certain issues, such as women dress-code or allowed occupations for womens?

Do you know the reasons of the difference? Try to investigate whether the differences are still within God's upper and lower Legal Limits by using the references above?

Please, share your stories in the discussion page

title: Islam Way of Life/Limits


text:
Handbook of Genetic Counseling/Turner Syndrome-2

Turner Syndrome

Contracting

 * Introductions and acknowledge prior contact
 * Forewarning to provide an opportunity for cognitive and emotional preparation
 * When we met two weeks ago, Dr. Doktour ordered a chromosome test to see if you had any missing or extra genetic material that might explain why you have a shorter stature and why you haven't started menstruating.
 * Acknowledge previous visit- discussion of Turner syndrome
 * As we discussed last time, individuals with Turner syndrome only have one X-chromosome instead of the expected two copies (show visual aid to reinforce).
 * Women that have Turner syndrome are unable to reproduce because ovulation does not occur.
 * Acknowledge her pain
 * I know that you and your fiancé were really looking forward to having children, I'm so sorry it turned out this way.

-An edit from someone with experience receiving this diagnosis: A very helpful thing to say instead in that moment is something along the lines of, "If you want to be a mother, you will be."

Discuss agenda
(Assess understanding throughout discussion)
 * There are many areas that we can discuss today. We can talk about as much or as little about Turner syndrome as you would like.
 * Areas we can discuss today
 * How this happened, what the diagnosis means for you, reproductive options.
 * What would you like to talk about?
 * How did this happen?
 * Genes and chromosomes- less specific if needed
 * Some of your genetic material is missing- you only have one X-chromosome instead of the expected two copies.
 * The X chromosome is one of the sex chromosomes and two copies are required for sexual development in a female to occur as expected.
 * Reinforce (considering family hx. of short stature and "late bloomers") that Turner syndrome does not run in families

What this diagnosis means for you and your health

 * Mild physical differences: short neck, low hairline, broad chest, small fingernails, and often have many moles.
 * Women with Turner syndrome do not look very different from women that do not have Turner syndrome. In most cases, you and I would not be able to tell the difference-usually only someone that is trained to look for these differences would be able to do so.
 * Medical complications:
 * Endocrine:
 * Ovaries do not develop properly therefore the hormones produced by the ovary, estrogen and progesterone, are not produced.
 * These hormones are required for:
 * Development and maintenance of secondary sexual characteristics
 * Preparation of the uterus for pregnancy
 * Development of the mammary gland
 * Hormone replacement regimen- to promote 2ndary sexual characteristics and to initiate menses.
 * Hypothyroidism (insufficient thyroid secretion of T3 and T4) is common in Turner syndrome
 * Renal anomalies-
 * Sometimes the kidneys fuse together or there is a duplication of the ureters (this just means that you are at a higher risk of UTI's)
 * Order renal ultrasound
 * Cardiac anomalies-
 * Coarctation of the aorta, VSD, bicuspid aortic valve
 * Some are born with heart defects- (about 15-20%)
 * Risk for other complications (aortic aneurysm) in those that have coarctation or bicuspid aortic valve.
 * Hypertension is also commonly seen in individuals with Turner syndrome.
 * Risk increases with age and obesity
 * Will need routine blood pressure checks
 * We will need to order an echocardiogram (type of ultrasound that we can use to visualize all of the internal parts of the heart)
 * Hearing
 * Increased frequency of chronic ear infections (80%)
 * Some hearing loss may be due to chronic infections
 * Ophthalmologic:
 * Ocular problems are present in ½ of girls
 * Strabismus
 * Ptosis
 * Hyperopia (far-sightedness)
 * Myopia (near-sightedness)
 * Cataracts
 * Nystagmus
 * Musculoskeletal:
 * Short stature (100%)
 * Cubitis valgus (increased carrying angle at the elbow)
 * Lymphadema-
 * Puffiness in utero is a major feature of Turner syndrome
 * TAKE HOME MESSAGE: we will want to schedule some tests for you:
 * Echocardiogram
 * Renal ultrasound (also evaluate ovaries and uterus)
 * Routine blood pressure checks- monitor hypertension
 * See an endocrinologist for hormone replacement
 * Screen for thyroid function annually
 * Family planning options:
 * (Spontaneous pregnancies have occurred in mosaics-some cells have both X's and some only have one X)- don't discuss unless client wishes to do so.
 * Artificial reproductive therapy (ART)- although ovulation does not occur, the uterus is usually structurally normal, which means that women with Turner's syndrome are capable of carrying a child.
 * In-vitro fertilization: donor egg + fiancé's sperm, create embryo in the laboratory and then implant the embryo into your uterus.
 * Expensive though
 * Treat with hormones, estradiol and progesterone early in pregnancy until sufficient placental production of hormones
 * Adoption
 * Can provide information on centers in the area, if you decide this is an option for you.
 * Life Expectancy:
 * Studies have shown that individuals with Turner syndrome have a normal life expectancy if no heart or renal defects are present.

Psychosocial Counseling/ Questions

 * How are you feeling right now?
 * What questions do you have?
 * Am I making sense to you?
 * Tell me what you are feeling right now…..
 * Normalize…it is very normal to feel this way
 * Acknowledge the patient's reaction to the news
 * This must be very overwhelming for you
 * I can see that this is very hard for you….I'm sorry for your pain
 * How have you handled difficult situations in the past?
 * Do you have family/friends in the area?
 * Provide hope…discuss family planning options….no decreased lifespan…a lot of the medical problems associated with TS, we know that you do not have.

Planning and following through

 * I'm going to call you tomorrow afternoon, is that ok?
 * I have scheduled an appointment to meet next week. Will your fiancé be back in town?
 * I will schedule appointments for you to have testing done and will notify you with those dates.
 * These are not urgent tests that have to be done tomorrow. You have lived 27 years with Turner syndrome. Nothing has changed, except that now you know why you have short stature and haven't begun menstruating.

Support Resources

 * Patient fact sheet information: (print off copy for patient)
 * http://www.endo-society.org
 * http://www.turner-syndrome-us.org
 * http://www.tensiometre24.com
 * Provides information on the medical facts of Turner syndrome, members only site where there are chat rooms, message boards, and newsletters.
 * This site will provide a lot of the same information we talked about today.

Resources

 * American Academy of Pediatrics Committee on Genetics (1005). Health supervision for children with Turner syndrome. Pediatrics. 96: 1166-1173.
 * Sybert VP (2001). Turner Syndrome. In: Management of Genetic Syndromes. Eds: Cassidy SB, Allanson JE. Wiley-Liss, Inc.
 * Dr. Schorry's clinical genetics lecture notes.

Support Resources

 * http://www.turner-syndrome-us.org
 * Provides information on the medical facts of Turner syndrome, members only site where there are chat rooms, message boards, and newsletters.

Tests that we will be ordering

 * Echocardiogram
 * Renal ultrasound (also evaluate ovaries and uterus)
 * Routine blood pressure checks- monitor hypertension
 * Screen for thyroid function annually
 * We will also schedule you an appointment to see an endocrinologist to discuss hormone replacement therapy.


text:
Handbook of Genetic Counseling/VATER Association

VATER Association

What is VATER Association?

 * VATER association is an acronym for a sporadic constellation of findings that occur together more often than by chance alone.
 * The major anomalies associated with this constellation are: Vertebral defects, Anal atresia, Tracheoesophageal fistula, Esophageal atresia, and Renal/Radial defects.
 * The term VACTERL association is sometimes used in place of VATER because two additional features (cardiac and limb/radial) are more specifically identified in the acronym.

Diagnosis

 * The VATER/VACTERL association represents a core group of 7 anomalies (see above), but very few patients have all 7 features.
 * The average number of features per patient is 3 to 4, but no minimum criteria have been agreed on regarding which of these features or what combination of these constitutes a secure diagnosis.
 * Some propose that at least 1 anomaly in each of the 3 geographic regions of involvement (limb, thorax, and pelvis/lower abdomen) should constitute a "secure" diagnosis.
 * Thus, qualification as "probable" VATER/VACTERL association requires at least 2 anomalies in each of 2 geographic areas to qualify.
 * VATER/VACERL represents a classic example of a "diagnosis of exclusion." There is no facial gestalt to aid pattern recognition, and its core features are commonly found in other situations and syndromes.
 * Thus, clinicians need to exclude all other similar clinical entities, to have obtained a normal chromosome analysis, and to exclude teratogenic exposure during early gestation.

Prognosis

 * The long-term prognosis for children with the VATER/VACTERL association is variable.
 * Each surgical anomaly seems, prognostically, independent of the other.
 * If each surgical defect can be satisfactorily repaired and/or medically treated, the prognosis is excellent. If some defects cannot be totally repaired or persist with sequelae, then the prognosis is the sum total of the residual problems.
 * There is generally a good prognosis for intelligence.

Features of VATER Association
o Single umbilical artery o Cleft lip o Polydactyly (preaxial) o Small intestinal atresia o Auricular aberrations o Genital/urogenital defects
 * Other anomalies and abnormalities that occur in the VATER/VACTERL association are:
 * Rare instances of caudal regression and lower extremity defects have also been reported.
 * Intrauterine growth retardation of unexplained etiology is occasionally present.
 * The differential diagnosis list when considering the VATER/VACTERL association is long because so many anomalies can be found as components of other syndromes.
 * Congenital heart failure, renal dysfunction, or gastrointestinal disorder can cause poor growth; therefore adequacy of caloric intake should be assessed. Gastrostomy tube feedings may be necessary.
 * Early psychomotor delay, and behavioral problems can occur.
 * Poor body image may be noted especially in children with limb deficiencies, short statures, complicated anal atresia with persistent intestinal problems, or external genital abnormalities.
 * Vertebral anomalies are generally not extensive and most often occur in upper to mid thoracic and lumbar regions, with sacral and lower cervical defects being less common. Hemivertebrae are most common, but dyssegmented and fused vertebral bodies can also be found.
 * Limb anomalies are restricted to the upper limbs and are usually preaxial, involving underdevelopment or agenesis of the thumbs and radial bones. These defects are usually bilateral but often asymmetric in degree.
 * 50-60% of patients with VATER/VACTERL association have either tracheoesophageal fistula or esophageal atresia. The majority of children with these abnormalities survive if their other associated anomalies are amenable to therapy.
 * Approximately 37% of patients with tracheoesophageal fistula and esophageal atresia have cardiac defects.
 * Anal atresia (imperforate anus) requires immediate attention. The presence of anal atresia is associated with an increased incidence of external anomalies of the genitalia, internal anomalies of the urinary and reproductive tracts, and vertebral defects of the lumber and sacral spine.

Management

 * VATER/VACTERL association is very complex from the clinical management standpoint because all 7 of its core features may necessitate surgical intervention.
 * There are potentially an impressive number of specialists that could be required for any one child including a geneticist, orthopedist, urologist, cardiac surgeon, nephrologist, gastroenterologist, pulmonologist, physical therapist, nutritionist, psychologist, and more.
 * The need for long-term follow-up by most of the specialists is labor intensive for the child and family.
 * Physical therapy and infant stimulation are important because of the frequent and prolonged hospitalizations.

Prevalence and Inheritance

 * VATER association is a relatively common, nonrandom multiple-malformation condition.
 * The incidence is reported to be 1.6 in 10,000 (Cassidy).
 * No consistent or recurring etiology has been established for the VATER/VACTERL association. It has been more frequently reported in the offspring of diabetic mothers.
 * Most cases occur as sporadic events with low recurrence risk.
 * It is generally felt to be a heterogeneous disorder with the various yet-to-be established etiologies working through a common embryological pathway.

Recurrence Risks

 * The pattern of malformation has generally been a sporadic occurrence; thus, there is probably a low recurrence risk (<1%).

Patient Resources
o C/o Greg and Terri Burke o (301) 952-6837 o www.vaterconection.org/main.htm
 * TEF/VATER International Support Network
 * VATER Connection Web Site

Definitions

 * Esophageal atresia: congenital failure of the esophagus to develop
 * Anal atresia: imperforate anus, anus without an opening
 * Tracheoesophageal fistula: congenital defect linking the trachea and the esophagus, resulting from failure of the lungs to separate from the GI tract during development. Surgery is needed to prevent recurring episodes of aspiration pneumonia in the newborn.
 * Hypospadias: abnormal congenital opening of the male urethra upon the undersurface of the penis.
 * Anoplasty: reconstructive surgery of the anus
 * Colostomy: opening of a portion of the colon through the abdominal wall to its skin surface.
 * Nissen fundoplication: surgical correction of esophageal hernia or gastroesophageal reflux, by wrapping the gastric cardia with adjacent portions of the gastric fundus. The procedure re-establishes the gastroesophageal angle and prevents intrathoracic displacement of the stomach.


text:
Cookbook:Creamy Delight Smoothie

| Beverages

Ingredients

 * 1 banana
 * 6 strawberries
 * 1 cup milk
 * 3 tbsp yogurt
 * 5 scoops vanilla ice cream
 * 1 cup cream
 * 2 tsp apple juice
 * 2 tsp vanilla extract

Procedure

 * 1) Purée all ingredients together in a blender.

title: Cookbook:Creamy Delight Smoothie


text:
Handbook of Genetic Counseling/Velo-Cardio-Facial Syndrome (VCF)

Velo-Cardio-Facial Syndrome (VCF)

Introduction

 * Who referred you here today?
 * What specific questions would you like to have answered today?
 * What information have you already been given?

What is VCF?

 * VCF is an alternate name used in past literature for the condition currently referred to as 22q11 Deletion Syndrome.
 * A highly variable syndrome of associated anomalies including congenital heart disease, dysmorphic features, palate anomalies, and some degree of learning disabilities or mental retardation
 * Children with VCF often have feeding problems and speech problems

Etiology and Natural History

 * VCF occurs in about 1/4000 live births
 * About 90% of people with VCF have a deletion at 22q11.2
 * Most cases are a result of a new mutation
 * In 10-20% of cases one parent also has a deletion and VCF phenotype

Recurrence Risk

 * Children of those with VCF have a 50% chance of inheriting the deletion
 * Parents of a child with a new mutation have a very low risk of having another child with the mutation

Clinical Features

 * Heart Defects
 * Congenital heart disease occurs in about 74% of patients
 * These defects are generally conotruncal defects
 * Tetrology of Fallot - 22%
 * Interrupted Aortic Arch - 15%
 * Ventral Septal Defect - 13%
 * Truncus Arteriosus - 7%
 * Other Defect - 17%
 * Palate
 * Palatal Defects occur in 69% of patients
 * Velopharyngeal incompetence (VPI) is the most common defect (27%)
 * Disorder of the velopharyngeal valve which is required for normal speech
 * Can lead to hypernasal speech, nasal air emission, or other speech problems
 * Submucosal and overt cleft palate are also common
 * Feeding
 * 30% of patients have feeding problems
 * nasal regurgitation is the most common problem
 * many feeding problems are a result of the palate defects
 * Thymus
 * Many patients (specifically those with DiGeorge sequence have a dysplastic or absent thymus)
 * This results in a decrease in T-cells leading to decreased immune response
 * Absent thymus can also cause hypocalcemia which may lead to seizures
 * Dysmorphology
 * A variety of dysmorphic features are associated with VCF
 * Microcephaly
 * Narrow palpebral fissures
 * Wide nasal root
 * Bulbous nasal tip
 * Thin upper lip
 * Micrognathia
 * Short stature
 * Eye and ear abnormalities
 * Neurological Defects
 * Most patients have some degree of learning disabilities or mental retardation
 * Intelligence generally in low-normal range
 * Often have language difficulties
 * Specifically with reading comprehension and expressive language
 * Other associations
 * Kidneys: may be polycystic or dysplastic
 * Growth: may be smaller in some cases due to lack of growth hormone
 * Rheumatoid Arthritis: more frequent than general population

Molecular Testing

 * Chromosomal region is called DGCR
 * FISH analysis can be used to identify a deletion on chromosome 22
 * Chromosome analysis should be run at the same time in order to locate the occasional disruption caused by a translocation of part of 22

Management

 * Monitor heart function
 * Repair defects if necessary
 * Evaluate palate
 * Intervention for feeding problems
 * Repair of palate if necessary
 * Monitor blood calcium levels
 * Renal ultrasound to check kidneys
 * Monitor lymphocytes
 * Prevent use of live virus vaccines in patients with reduced immune response
 * Provide speech therapy early in development
 * Provide early intervention for school

Psychosocial Issues

 * Concern over what problems to anticipate with VCF
 * Parents may feel guilt or anger overdiagnosis
 * Confusion if mutation not found
 * Self-esteem issues for children with VCF due to learning disabilities
 * Social stigma due to speech difficulties

Resources

 * "Faces of Sunshine: The 22q11.2 Deletion" Ed. Donna McDonald-McGinn, Brenda Finucane and Elaine Zackai. 2000.


text:
Cookbook:Fruit for the Day Smoothie

Ingredients

 * 1 can (397 g / 14 oz) Mandarin oranges (including syrup)
 * 2 frozen bananas, peeled and sliced
 * 2 cups (160 g / 5.6 oz) frozen strawberries
 * 1 ½ cups (375 ml / 12.7 oz) milk

Procedure

 * 1) Add all ingredients to a blender in the order listed above.
 * 2) Hold down the lid, and blend on low speed for 30 seconds.
 * 3) Blend on high speed for 1 minute.
 * 4) Pour into a glass and enjoy.

title: Cookbook:Fruit for the Day Smoothie


text:
Cookbook:Easy Orange Smoothie

Ingredients

 * 1 small can frozen orange juice
 * 1 cup skim milk
 * 1 cup water
 * 1 tsp vanilla extract
 * ¼ cup sugar
 * 14 ice cubes, crushed

Procedure

 * 1) Place all ingredients in blender, and blend until smooth.
 * 2) Serve and enjoy.

title: Cookbook:Easy Orange Smoothie