text:
Handbook of Genetic Counseling/Ovarian Cancer

Ovarian Cancer

Contracting

 * Before we get started, I want to give you a chance to ask any questions or express any concerns that you may have.
 * What issues do you want to make sure we discuss? What do you want to gain from our session today?
 * Our plan:
 * talk about your medical history and diagnosis
 * discuss your family history in a little more detail
 * talk about the genetics of hereditary cancers
 * we'll explain what we see and discuss your risks
 * talk about genetic testing - what it tests, limitations
 * discuss ways for you to stay healthy

Medical History

 * Tell me how you got to this point. How was your ovarian cancer diagnosed?
 * Fill out intake with details.
 * Any other medical illnesses, surgeries, or hospitalizations?

Family History

 * Update pedigree with details. A pedigree is our "physical exam". Gives us clues as to whether the cancer is hereditary. It's important to know who has AND who doesn't have cancer.
 * Very specific questions about the cancer in different family members
 * Age at diagnosis
 * Current age & screening practices
 * Age at death & specific cause of death
 * Primary site of cancer (type, location, stage, laterality)
 * Metastasis or any new primary cancers
 * Methods of treatment/surgery
 * Any types of precancerous lesions
 * Ethnic background
 * Environmental exposures
 * Lifestyle issues (diet, exercise, stress)
 * Screening habits of "unaffected" relatives
 * Any other medical conditions that may be associated with cancer
 * any family hx of early heart attacks, blindness, deafness, birth defects, or multiple miscarriages

Cancer Epidemiology

 * Cancer is the uncontrolled growth of cells. All cancers are genetic, but not all are inherited. It is a multifactorial disorder, caused by both genetic and non-genetic factors.
 * Cancer is a very common disease. 1 in 2 men and 1 in 3 women will develop some form of cancer in their lifetimes. The most common cancer sites are lung, breast, prostate, and colon.
 * In the U.S., 1 in 55 women will develop ovarian cancer (1.8% lifetime risk)
 * 5-10% of all ovarian cancer is hereditary (meaning that it runs in families)
 * 90% of this is caused by a BRCA1 or BRCA2 mutation
 * In the U.S., 1 in 8 women will develop breast cancer over their lifetimes.
 * Average age of developing cancer is 62 (2/3 of the women will be over 55)
 * 5-10% of all breast cancer is hereditary. Of this, 2/3 (66%) of it is due to a BRCA1 or BRCA2 mutation
 * This gene is the link between breast and ovarian cancer.

Red Flags

 * How do we know when a cancer is hereditary? We look for clues (red flags).
 * What makes us suspicious:
 * more than one generation affected
 * multiple close relatives affected on the same side of the family
 * early age of onset (before 50)
 * bilateral cancer or more than one type of cancer in the same person
 * rare or unusual cancers

Genes and Chromosomes
through a family
 * Hereditary cancers are caused by a change in a specific gene that is passed on
 * Genes are made of DNA. They have all the instructions for how our bodies grow and develop.
 * When there is a change in a gene, it causes the cell to not work properly, so it can grow out of control and become cancerous.
 * Genes are packaged on chromosomes. Chromosomes come in pairs, and we inherit one from mom and one from dad.
 * This gene is autosomal dominant, so only need one copy of it to inherit a higher risk of cancer. There is a 50% chance of getting it from our parents. If we carry the gene, then we have a 50% chance of passing it on.


text:
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title: User talk:85.100.227.47


text: Talk:Russian/Numbers

title: Talk:Russian/Numbers


text:
Handbook of Genetic Counseling/Pallister-Killian Syndrome

Pallister-Killian Syndrome

Genetic Etiology

 * Tetrasomy 12p (mosaicism)

Incidence and carrier frequency

 * Very rare disorder
 * Affects males and females in equal numbers
 * >30 cases reported in the literature

Risk to various family members

 * Sporadic inheritance, extremely rare
 * No increased recurrence risk

Clinical features

 * Typical findings:
 * Hypotonia
 * sparse scalp hair
 * a high forehead with frontal bossing
 * a coarse face
 * an abnormally wide space between the eyes
 * broad nasal bridge
 * highly arched palate
 * epicanthal folds
 * large ears with lobes that are thick and protrude outward.
 * Additional features many include:
 * congenital heart defects
 * diaphragmatic hernia
 * hypopigmentation
 * extra nipples
 * seizures
 * droopy upper eyelids
 * strabismus
 * contractures
 * cognitive delays, speech delays
 * mental retardation
 * stenosis of the external auditory canal
 * abnormal opening in the anus
 * hypoplastic lung
 * abnormalities of the genitourinary system
 * skeletal malformations.

Testing/Diagnosis

 * the chromosome abnormality in Pallister-Killian Mosaic Syndrome is limited to specific cell types
 * mechanism and parental origin of the isochromosome 12p can usually not be determined
 * diagnosis is usually made from a chromosome study of skin cells (fibroblasts)
 * a blood chromosome study usually shows normal chromosomes
 * peripheral blood lymphocytes are continually dividing
 * they may lose the extra chromosome with their frequent divisions
 * fibroblasts normally cycle less frequently, don't lose the extra chromosome
 * Other reasons to test skin cells:
 * During the 3rd week of fetal development gastrulation determines 3 germ layers
 * Ectoderm: gives rise to the epidermis (skin) and central nervous system
 * Endoderm: gives rise to the inner lining of the digestive tract and also the linings of tissues that sprout from the digestive tract, such as the respiratory system, liver, and pancreas
 * Mesoderm: gives rise to tissues such as bones, muscle, blood, and connective tissue
 * If a chromosome error arises after these tissues differentiate, there could be an error in the skin cells that is not present in other tissues that came from other germ layers

Surveillance, management, and treatment options

 * There is no specific therapy for individuals with Pallister-Killian Syndrome
 * Because of poor prognosis, generally only supportive care
 * Affected children may benefit from early intervention programs and special education

Differential diagnoses

 * Fryns syndrome

Psychosocial issues

 * Grief over loss of "normal baby"
 * Shock over unexpected problems
 * Worry about prognosis
 * Uncertainty about testing and procedures
 * Financial considerations, what will treatment cost?
 * Who is their support network?
 * Effects on relationships (parent/child)
 * Concern about telling other family members
 * Future reproductive decisions
 * Possible disruption of marital relationships or family dynamics

Support groups

 * PKS Kids
 * PO Box 94
 * Florissant, MO 63032-0094
 * email: gpeters@pkskids.net
 * Home page: http://www.pkskids.net

 * UNIQUE - Rare Chromosome Disorder Support Group
 * P.O. Box 2189
 * Surrey Intl CR3 5GN
 * Phone #: 4401883 330766
 * 800 #:
 * e-mail: info@rarechromo.org
 * Home page: http://www.rarechromo.org


text:
Handbook of Genetic Counseling/Pancreatic Cancer

Pancreatic Cancer

Pancreatic Cancer

 * Incidence is more than 29,000 new cases/year in US
 * Fifth leading cause of cancer death
 * 4.1% five-year survival rate is lowest of all cancers
 * About 9-10% of pancreatic cancer is familial
 * Pancreas is a gland located in the abdomen between the stomach and the spine
 * Responsible for producing insulin, glucagon, and other hormones
 * Releases digestive juices through series of ducts leading to common bile duct
 * Risk factors for pancreatic cancer
 * Smoking - increases risk 2-3 times
 * Age - most cancers diagnosed between 60 and 80 years
 * Diabetes
 * Chronic pancreatitis
 * Long-term inflammation of the pancreas
 * Especially inherited form of the condition
 * Family history
 * Risk increases by 4.7% if first degree relative has been diagnosed
 * Increases by 7.3% if diagnosis was made before age 60
 * Increases by 12.3% if multiple primary cancers in family
 * Males and African-Americans may be at increased risk
 * Diets high in fat may increase risk

Diagnosis and Surveillance Options

 * Possible symptoms
 * Pain in upper abdomen or upper back
 * Yellowing of skin and eyes, dark urine due to jaundice
 * Weakness
 * Loss of appetite
 * Nausea and vomiting
 * Weight loss
 * Physical exam
 * Look for signs of jaundice or changes in area near pancreas
 * Check for ascites (build-up of fluid in abdomen)
 * Lab tests
 * Blood, urine, and stool samples
 * Check for bilirubin that may be high if tumor blocking common bile duct prevents its passage
 * CT Scan
 * Produces detailed picture of abdomen
 * Can provide information about nature and location of tumors, resectability
 * Ultrasonography
 * Transabdominal ultrasound
 * Endoscopic ultrasound (EUS)
 * Pass thin, illuminated optic instrument down mouth into stomach
 * Ultrasound device at tip of endoscope takes images of pancreas and surrounding areas
 * Endoscopic Retrograde Cholangiopancreatography (ERCP)
 * Pass endoscope through mouth and stomach into first part of small intestine
 * Inject dye through catheter into ducts
 * Take X-rays to determine if ducts are narrowed or blocked by tumor
 * Percutaneous Transhepatic Cholangiography (PTC)
 * Dye injected through needle inserted through skin into liver
 * Dye moves freely through bile ducts unless blocked
 * X-rays can show if dye has moved through ducts
 * Biopsy
 * Fine-needle aspiration
 * During EUS or ERCP
 * Open abdomen during operation
 * Laparoscopy
 * Uses several small incisions and TV camera to visualize organs in abdomen
 * Usually only used if CT scan shows evidence of metastases

Treatment

 * Pancreatic cancer is currently difficult to treat so participation in clinical trials is often recommended
 * Surgery
 * May be used alone or in combination with radiation or chemotherapy
 * Whipple procedure
 * If tumor is in head of pancreas
 * Remove head and part of small intestine, bile duct, and stomach
 * Distal pancreatectomy
 * Surgeon removes body and tail of pancreas
 * May also remove the spleen
 * Total pancreatectomy
 * Remove entire pancreas
 * Also remove part of small intestine and stomach, and all of common bile duct, gallbladder, spleen, and nearby lymph nodes
 * Create bypass or insert stent if tumor is blocking common bile duct or duodenum
 * Relives jaundice and pain resulting from blockage
 * Done if cancer cannot be completely removed surgically
 * Side effects of removal of all or part of pancreas
 * Diet control and medication may help with food digestion
 * Diarrhea, pain, cramping, and feelings of fullness are common
 * Radiation therapy and chemotherapy often used to destroy cancer cells

Genetic Conditions Associated with Pancreatic Cancer

 * Familial Atypical Multiple Mole Melanoma (FAMMM)
 * Due to mutations in p16 tumor suppressor gene
 * TP16 (CKDN2) located at 9p21
 * Affected individuals develop multiple nevi, atypical nevi, melanomas, and pancreatic cancer
 * Peutz-Jeghers Syndrome
 * Due to mutations in LKB1 (STK11) gene at 19p13.3
 * Causes multiple hamartomaous polyps of GI tract and pigmented macules on lips, buccal mucosa, and digits
 * Increases risk to develop cancers
 * In women: breast, pancreas, uterus, and ovary
 * In men: colon, pancreas, lung, or testes
 * Hereditary Breast-Ovarian Cancer Syndrome
 * Due to mutations in BRCA2 tumor suppressor gene at 13q12
 * Most common inherited predisposition to pancreatic cancer identified to date
 * Mutations in BRCA2 have been identified in individuals with no family history of breast or ovarian cancer
 * Estimated that carriers of 6174delT have 10-fold increased risk of developing pancreatic cancer
 * Increases risk for breast, ovarian, prostate, and colon cancers also
 * HNPCC
 * Due to mutations in mismatch repair genes, including MSH2 and MLH1
 * Microsatellite instability has been identified in ~4% of pancreatic cancers
 * Should be considered in patients with family history of colon cancer
 * Increases risk for colon/rectum, endometrium, ovarian, urinary tract, stomach, and small intestine also
 * MEN1
 * Due to mutations in menin tumor suppressor gene at 11q13
 * Associated specifically with insulinomas (10%) or gastrinomas (40%)
 * Can cause tumors on parathyroid and pituitary glands also
 * Hereditary Pancreatitis
 * Due to mutations in cationic trypsinogen gene on 7q35
 * Block inactivation of trypsin, resulting in autodigestion of pancrease
 * Increase in pancreatic cancer may be secondary to chronic injury and repair
 * Clinical testing available through University of Pittsburgh
 * Penetrance of mutations is only 80%

Psychosocial Issues

 * Worry about the future - caring for themselves, family, etc.
 * Financial concerns
 * Concerns about treatments and side effects
 * Concern about necessity of frequent hospital visits, home care, etc.
 * Feelings of guilt, anxiety, fear surrounding potential diagnosis of hereditary syndrome

Resources

 * The National Familial Pancreas Tumor Registry
 * Dr. Ralph H. Hruban, Director
 * Baltimore, MD 21231-2410
 * Phone: (410) 955-9132

 * Hereditary Pancreatitis Registry
 * Dr. Whitcomb or Dr. Lowenfels
 * The Midwest Multicenter Pancreatic Study Group
 * Phone: 888-PITT-DNA

 * National Cancer Institute
 * Phone: 1-800-4-CANCER
 * http://cancer.gov


text: User:Tim Thomason

title: User:Tim Thomason


text:
Wikijunior:Big Cats/Clouded leopard

Clouded leopards are not truly leopards at all but they spend a great deal of time in trees, just as the true leopards of Africa do.

Where do clouded leopards live?
Clouded leopards live throughout southern China, the eastern Himalayan Mountains, south-east Asia, and some parts of Indonesia. They prefer to live in tropical or subtropical forests, yet they can also be found living in mangrove swamps and grasslands.

The clouded leopard is a medium-sized wild cat found in the forests of Asia. Little is known about the wild behavior of clouded leopards due to their extremely secretive nature. Much of our understanding of this cat’s natural history and behavior is a result of observations of them in captivity.

What do clouded leopards look like?
At adult age a clouded leopard will range from somewhere between two and a half feet, nose to rump, to three and a half feet. The clouded leopard has short legs for its size. It also has the longest canine teeth (2-inch fangs) for any similarly sized cat species that lives today. Only the extinct sabretooth cats had longer canine teeth for their body size.

Clouded leopards are excellent climbers and their major prey animals live in trees. Short flexible legs, large paws, and keen claws combine to make them very sure-footed in this environment. The clouded leopard's tail can be as long as the rest of its body and helps to maintain the cat's balance while moving through the trees. Amazingly, these cats can hang upside-down under branches, and can even climb down tree trunks head-first. Other cats cannot do this because their claws are not shaped in the same way.

The beautiful pattern of the clouded leopard's fur is its most interesting feature. The large square rosettes look like clouds to some people, and that is how they got the name "clouded leopard." Other people think the blotches look more like mint leaves, so they are also called "mint leopards."

What do clouded leopards eat, and how do they catch their prey?
While not much is known about their behaviour in the wild, their prey is thought to be mostly mammals that live in trees, particularly monkeys, along with small mammals, deer, birds, porcupines, goats, wild boar, young buffalo, and domestic livestock. Clouded leopards will stalk their prey in the trees, then jump down from their perch and attack from behind, but clouded leopards are also skilled at hunting on the ground.

Fun facts
See how much you know about the clouded leopard:
 * They can climb down tree trunks head first.
 * Like marbled cats and margays, they will sometimes hang head-down from branches using their hind legs.
 * Young clouded leopards are born with spots that become open squares as they grow older.
 * Clouded leopards have extremely flexible ankles in their hind legs, which aids them in climbing.
 * Clouded leopards have the longest canine teeth in proportion to its skull and body size, in similarity to the extinct saber-toothed tiger.

For more information
Next Topic: Marbled Cats
 * Wikipedia: Clouded leopard

Wikijunior Großkatzen/ Nebelparder

title: Wikijunior:Big Cats/Clouded leopard


text: User talk:170.235.223.10

title: User talk:170.235.223.10


text:
Handbook of Genetic Counseling/Partial Trisomy 11q (q14-q21)

Partial Trisomy 11q (q14-q21)

Introduction

 * Introduce myself and others
 * Assess concerns and what they hope to gain from the session
 * Discuss reason for follow-up
 * Provide overview of session

Elicit interim medical history

 * Any illnesses/hospitalizations/surgeries since last visit in September?
 * Current medications
 * Any recent medical tests or procedures (since September)?
 * Immunizations up to date?
 * Review of systems

Elicit interim family history

 * Any newborns in the family?
 * Any new information about health problems in family members?
 * Any significant changes in family members' health?

Psychosocial update?

 * Any changes in work?
 * Who takes care of during the day?
 * Any plans for more children?
 * How are finances after paying for ____'s medical needs? Any assistance used or needed?

Genetic etiology

 * Partial trisomies are usually de novo
 * Possible mechanisms for formation of a partial trisomy/duplucation:
 * Unequal crossing over during homologous chromosome recombination in meiosis, chromosomes mispaired resulting in duplication in one set of homologous chromosomes and deletion in one set of homologous chromosomes
 * Parental gonadal mosaicism-One of his parents could have duplication of this region in some germ cells (caused by same mechanism as above)
 * Recurrence risk for parents to have another child with Patient's chromosome rearrangement is less than 0.5% (probably MUCH less, but in case of gonadal mosaicism, we should say this number)
 * Risk for any chromosome abnormality in future pregnancy: 1/417 at age 29, 1/384 at age 30 (from Maternal-Fetal Medicine)
 * Risk for Patient to have a child with the same chromosome abnormality is about 50%
 * Homologous chromosome pairing during meiosis requires the chromosomes to contort in order to pair up properly-this can lead to problems during crossing over, where further chromosome abnormalities could occur, as well as formation of an extra abnormal chromosome
 * Fertility may be a problem with Patient, as it commonly is in people with chromosome abnormalities (especially males) and so this may be something the parents or Patient will want to assess after puberty

Molecular genetics

 * People with duplications in different regions of 11q have been identified in the literature, but none with the same region as Patient
 * Even though some of these people's duplicated regions may overlap slightly with Patient's duplicated region, there are very different genes duplicated in those people, and so we would not expect Patient to have the same effects
 * Some of the documented literature:
 * Delobel B, Delannoy V, Pini G, Zapella M, Tardieu M, Vallee L, Croquette MF. Identification and molecular characterization of a small 11q23.3 de novo duplication in a patient with Rett syndrome manifestations. Am J Med Genet. 1998 Nov 16;80(3):273-80.
 * de Die-Smulders CE, Engelen JJ. 11Q duplication in a patient with Pitt-Rogers-Danks phenotype. Am J Med Genet. 1996 Dec 2;66(1):116-7.
 * Legius E, Wlodarska I, Selleri L, Evans GA, Wu R, Smet G, Fryns JP. De novo 46,XX, dir dup (11)(q133.3-->q14.2) in a patient with mental retardation, congenital cardiopathy and thrombopenia. Clin Genet. 1996 Apr;49(4):206-10.
 * Lakshminarayana P, Suresh S, Suresh I, Sriram U, Jabeen G. Inherited 11q partial trisomy. Indian J Pediatr. 1995 Mar-Apr;62(2):247-50.
 * Multiple citations noting duplications of 11q in association with leukemias and lymphomas
 * Bader PI, Haney SM, Munsick RA, Schubert SR, Hodes ME. Brief clinical report: neural tube defects in dup(11q). Am J Med Genet. 1984 Sep;19(1):5-8.

Testing options

 * Chromosome analysis can detect MOST duplications and other chromosome anomalies (FISH may be required if abnormal region on chromosome is small)

Support groups

 * Unique The Rare Chromosome Disorder Support Group
 * http://www.rarechromo.org
 * P.O.Box 2189, Caterham Surrey CR3 5GN England
 * Telephone: 44 (0)1883 330766
 * E-mail: info@rarechromo.org
 * Web site: www.rarechromo.org
 * UK-based parent resource site for information on rare chromosome disorders.
 * More information-based than support-based, but has a discussion board and

appears to be up-to-date. "Little Yellow Book" is a great reference for parents available as a free pdf file. Good info on genes, chromosomes, and chromosome abnormalities.
 * Chromosome Deletion Outreach (CDO)
 * http://web.archive.org/19981203003403/members.aol.com/cdousa/cdo.htm
 * P.O. Box 724, Boca Raton, FL 33429-0724
 * Phone: 888.236.6880 (toll free)
 * E-mail: info@chromodisorder.org
 * Web site: www.chromodisorder .org
 * This site is a resource for parents of children with rare chromosome abnormalities.
 * It provides parents with contact information for people who know about specific

rare chromosome abnormalities. No one with Patient's specific duplication is listed; however, there may still be good resources for information and support.

Conclusion/future plans

 * How do you feel about Patient's health right now?
 * What do you envision when you think about Patient's future?
 * How do you feel about your risk for a child with a chromosome abnormality in future pregnancies?
 * How do you feel about Patient's reproductive possibilities?

Resources

 * Gardner and Sutherland. Chromosome Abnormalities and Genetic Counseling. 1989.
 * Thompson and Thompson. Genetics in Medicine. (5th ed.) 1991.


text:
Handbook of Genetic Counseling/Percutaneous Umbilical Blood Sampling (PUBS)

Percutaneous Umbilical Blood Sampling (PUBS)

Introduction

 * Welcome and acknowledge prior phone contact
 * Discuss the reason for referral
 * Elicit prior knowledge about Rh isoimmunization
 * Assess questions and concerns
 * Discuss overview of the session and explain relevance of each portion
 * Medical information and family history
 * Rh factor and isoimmunization
 * Treatment options for the fetus

Explain Genes and Chromosomes

 * Tell patient that we need to discuss genes and chromosomes so she can understand how we can tell that her baby is Rh negative
 * Dominant vs. recessive alleles and autosomal dominant inheritance

Rh Factor and Rh Isoimmunization

 * Rh refers to a protein that is sometimes present on the surface of red blood cells. If a person has this protein, they are Rh positive; if not, they are Rh negative
 * A person with Rh negative blood can develop antibodies against Rh positive cells if they are exposed to Rh positive blood. This can happen during pregnancy with an Rh - mother and Rh + fetus.
 * These antibodies attack the Rh + fetal cells
 * A medication called RhoGAM can be given to an Rh - mother so that she will not produce antibodies against her Rh + fetus
 * If the mother makes these antibodies, fetal blood cells will be destroyed and a serious condition called anemia can result. Another more life-threatening condition, immune hydrops fetalis, can also occur. This is the accumulation of water in the fetus, causing severe swelling. This can cause other organ systems in the baby to shut down or not develop correctly.
 * Even though Rh is the most common blood protein to cause sensitization in mothers there are other blood proteins such as Kell that can cause isoimmunization.

Explain PUBS
Discharge Instructions
 * Percutaneous umbilical blood sampling is a technique used to collect a sample of blood from a fetus through an umbilical vessel
 * "Percutaneous" refers to going through skin without puncturing or opening it
 * We can use this technique to do a blood transfusion directly into a fetus to treat anemia
 * Because of Rh incompatibility, we can't give the blood to the mother-it must be given directly to the baby
 * PUBS can be done starting at 16 weeks gestation until birth
 * The umbilical vessels connect the baby to the placenta (show on visual aid)
 * A doctor and an ultrasound technician will typically be in the room during the procedure. The mother may have someone come in with her if she chooses.
 * Mother will lie on an exam table on her back with her hands folded behind her head.
 * An ultrasound will be done first to determine the location of the fetus and the placenta
 * This is a special type of ultrasound, known as Color Doppler imaging. It allows the best view of the umbilical cord because it uses different colors to measure blood flow in the baby and allows the cord to be seen very easily.
 * The physician and ultrasound technician will look for the best place to access the umbilical artery-this is usually where the umbilical cord meets the placenta, since it is farthest from the baby. This is not always possible, so the physician will look for the best spot available. This may include a loop in the umbilical cord, the place where the umbilical cord enters the fetus, or the hepatic vein (inside the fetal body)
 * The entire procedure is done under ultrasound guidance
 * Once the insertion site has been determined, the mother's abdomen will be sterilized with betadeine
 * She will then be injected with a topical anesthetic at the insertion site
 * The physician will then insert a special needle into the mother's abdomen, through the uterus and into the umbilical vein
 * The needle is a 20 or 22-gauge needle (about the size used for drawing blood) and has a stylet inside of it
 * Even though a topical anesthetic has been given, the mother will still feel some cramping when the needle passes through the uterus. Most women say this is the most painful part and compare it to a strong menstrual cramp.
 * Once the needle has been inserted, the stylet will be removed and a syringe will be attached to the needle
 * The syringe will have a drug in it (heparin) to help with blood clots
 * A blood sample will then be taken to see if the baby is anemic. If that test (hematocrit) shows anemia, the procedure will continue.
 * Hematocrit allows us to determine whether or not fetal blood cells are being destroyed due to Rh incompatibility.
 * The baby will be given a neuromuscular blocking agent. This is to keep the baby from moving during the procedure.
 * The blood transfusion will then be given to the baby
 * The needle will then be removed and the physician will use ultrasound to check for fetal well-being
 * The entire procedure will take less than ten minutes
 * This procedure can reverse potentially detrimental conditions in a fetus. The overall survival rate for babies who have had a blood transfusion in utero is 84.7%. For babies without hydrops, the survival rate is 91.1%.
 * If necessary, the procedure will be repeated at 2-to-3-week intervals until 34–35 weeks of gestation.
 * If the mother is Rh negative, RhoGam needs to be administered within 72 hours.
 * After the test, avoid any strenuous activity for 24 hours. This includes standing for long periods of time, lifting, and exercising. A woman may return to work if her job doesn't require physical activity.
 * No sexual intercourse, douching, tub baths, or use of tampons for 72 hours.
 * Some minor cramping after the procedure is normal. If the cramps become severe, call a doctor. Also, call a doctor if leakage of clear fluid (amniotic fluid) or blood from the vagina, fever, unusual fetal activity, or any other unusual feelings occur.
 * A few days after the test, a mother should return for a follow-up ultrasound just to check on the baby. Also, serial ultrasounds are recommended to check for signs of hydrops.

Risks

 * If the placenta is located closer to the abdominal wall than the fetus is, the needle will pass through the placenta. This can cause maternal-fetal blood mixing.
 * RhoGAM will be given to the mother to prevent problems
 * 1-2% risk for pregnancy loss (this is above the 3-5% background risk)
 * Infection (chorioamnionitis) is another risk. Less common risks include blood clots in the umbilical cord, excessive bleeding (mother or baby), decreased fetal heart rate, and placental abruption. The overall risk of any of these things happening is between 1–6.7%, depending on the experience of the physician.
 * Loss rates are higher in fetuses who have genetic conditions, structural anomalies, or IUGR. Maternal complications are uncommon.

Other Testing Options

 * Amniocentesis
 * By using amnio, we can look at the amount of bilirubin in the amniotic fluid. This pigment is an indicator of hemolysis and can tell us if the baby is anemic. Also, we can measure the levels of DOD450 to tell if the fetus is anemic.
 * This is accurate during the third trimester, but not accurate in the second trimester.
 * This can diagnose anemia, but cannot treat it

Discuss Patient's Feelings About the Procedure

 * Emphasize the fact that this is entirely her choice


text:
Using GNOME/Sticky notes

< ../Applets

Sticky notes is an applet that displays windows that look like Post-its, little self-adhesive reminders.

To add to the panel, right click on the place you want the Sticky notes applet to appear, select Add to panel..., Sticky notes. It will appear as a yellow icon that looks like a block of post-it notes.

To create a note right click on the applet and select New Note. A window will appear in which you can type your message. The window can be resized by dragging either of the lower corners. The note will overlay any other windows and will follow you from workspace to workspace. To hide the notes select 'Show notes' from the applet icon menu to uncheck that item.

Sticky notes can be any colour you like, and any font. Right click on the title of the sticky and choose properties.

A locked sticky note cannot be edited.

title: Using GNOME/Sticky notes


text:
Handbook of Genetic Counseling/Phenylketonuria (PKU)

Phenylketonuria (PKU)

Introduction/Contracting

 * What is your understanding about why you are here?
 * When were you first told about the abnormal test?
 * Do you have any specific questions or concerns?
 * Outline the visit
 * We will be taking a family history
 * We will discuss the genetic basis of PKU
 * The medical geneticist will obtain some medical history and discuss medical management
 * The dietitian will also be visiting with you to discuss the specifics about diet

Family history
Basic Info to review with family
 * Get basic 3 generation pedigree
 * Ask about mental retardation, pregnancy losses, birth defects, learning difficulties, chronic health problems, children that died young, and PKU specifically
 * PKU is one of the disorders that is part of the newborn screening for in every state using a heel prick to get a blood sample
 * PKU can be successfully treated to prevent symptoms by maintaining a strict diet
 * There can be serious effects if the diet is not maintained especially during childhood
 * Mental retardation
 * Microcephaly
 * Delayed speech
 * Seizures
 * Eczema
 * Behavioral abnormalities
 * This is a diet that should be maintained throughout life.
 * The goal is to maintain phe levels below 6 mg/dl during childhood(some metabolic geneticists prefer to keep them below 5 mg/dl)
 * It is especially important that a woman with PKU maintain the diet before and during a pregnancy because high phe can harm the development of the baby.
 * Phe is an essential amino acid and is one of the building blocks of protein
 * When a baby has an excess amount of phe there are a couple of potential explanations as follows:
 * Phenyalanine hydroxylase (PAH) deficiency -- (most common cause, 98% of the time this is explanation)
 * (show diagram) This liver enzyme usually converts phenylalanine to another amino acid tyrosine
 * Sometimes the gene that tells the body how to make the PAH is changed and so it doesn't work as well or doesn't work at all
 * When this happens the path can be blocked and some by products will build up and cause the effects that can be seen in patients that are not on a well controlled diet
 * Inability to make or recycle a cofactor that is required to help PAH do its job.
 * This is rare and is found in about 2% of those with high phe.
 * HOWEVER it can't be ruled out completely until results of the test for this come back which will indicate if this is the explanation.
 * Because this cofactor also helps out in other important reactions in our bodies this can often be more severe sometimes referred to as atypical PKU

Details for Reference

 * tetrahydrobiopterine (BH4), the cofactor in the phenylalanine, tyrosine, and tryptophan hydroxylation reactions.
 * Defects in BH4 synthesis result from guanosine triphosphate cyclohydrolase (GTPCH) deficiency or 6-pyruvoyl tetrahydropterine synthase (PTPS) deficiency.
 * Impaired recycling of BH4 is caused by deficient dihydropteridine reductase (DHPR) or deficient pterin-4a carbinolamine dehydratase (PCD).
 * All of the HPAs caused by BH4 deficiency are inherited in an autosomal recessive manner.
 * They account for approximately 2% of patients with HPA. BH4 is also involved in catecholamine and serotonin biosynthesis.
 * The typical (severe) forms of GTPCH, PTPS, and DHPR deficiencies have the following variable, but common, symptoms:
 * mental retardation
 * Convulsions
 * disturbance of tone and posture
 * drowsiness
 * irritability
 * abnormal movements
 * recurrent hyperthermia without infections
 * hypersalivation
 * swallowing difficulties
 * Microcephaly is common in PTPS and DHPR deficiencies
 * Plasma phenylalanine levels can vary
 * Mild forms of BH4 deficiency have no clinical signs
 * PCD deficiency, sometimes referred to as "primapterinuria" is associated with benign transient hyperphenylalaninemia.
 * Treatment requires the normalization of blood phe concentration and restoration of the BH4-dependent hydroxylation of tyrosine and tryptophan by BH4 supplementation or by dietary modification, neurotransmitter precursor replacement therapy, and supplements of folic acid in DHPR deficiency

Three category classification
(when due to altered PAH) based on levels of phe when untreated
 * Classic PKU
 * due to a complete or near-complete deficiency of PAH activity
 * plasma phe concentrations above 20 mg/dl in the untreated state
 * must be treated by diet or brain damage will develop
 * Non-PKU Hyperphenylalinemia (also referred to as benign hyperphenylalinemia)
 * characterized by plasma phe concentrations consistently above normal when the patient is on a normal diet, but not high enough to cause impaired cognitive development
 * does not need to be treated by diet
 * Variant PKU (intermediate levels and requires some treatment)
 * intermediate levels between PKU and benign hyperphenylalinemia
 * many metabolic geneticists choose to treat these patients with a modified diet that may not be as restrictive as for those with classical PKU

Inheritance
(regardless of whether it is due to PAH gene or to a problem with the cofactor BH4, it is inherited in an AR fashion)
 * Autosomal means that the gene for PAH is on a chromosome other than the sex chromosomes
 * Recessive means that for a person to have clinical symptoms they must have inherited two copies of the altered gene one from each parent
 * We assume that you and your partner (husband) are carriers and don't have symptoms because you each have one functional copy
 * Two carriers have a one in four (or 25%) chance for each pregnancy that the baby will have PKU (draw out AR inheritance) and a 50 % chance of having a child that is a carrier just like the parents, a 25% chance of having a child with both functional copies

Prevalence

 * one in 15,000 live births in Caucasian populations and in Utah (carrier frequency in this population is approximately one in sixty)
 * Most literature still quotes one in 10,000 live births in Caucasian and East Asian pop. (one in 60 carrier rate)
 * Highly variable among populations
 * Turks one in 2600
 * Irish one in 4500
 * Japanese population one in 143,000
 * Finn and Ashkenazi Jewish populations one in 200,000

Psychosocial considerations
Molecular Genetic Testing
 * It can feel overwhelming to get a diagnosis and so much information
 * Reassure that we don't expect them to remember everything and that is why we'll be sending out a letter that will explain much of what we discuss
 * It is common for parents not to even know the test was done or what it means initially
 * Concerns about their ability to carry out the diet restrictions
 * Scared of the unknown
 * Provide information about the PKU picnic and potential to meet other families and see how children with PKU who are on diet since birth don't look or act any different than other children
 * Reassure them that it is possible to manage, but don't give the impression that it is super easy because it does take some special planning, time and effort
 * Reassure that we all carry genes that don't function properly, but we don't always know what they are unless we happen to find a partner that has one of the same altered genes (estimates are 4-6)
 * Explain that we are here to help them and they can call the dietician (Sharon) about diet questions or concerns and us about questions concerning the genetics of PKU
 * used primarily for genetic counseling purposes to determine carrier status of at-risk relatives and for prenatal testing
 * Over 380 different disease-causing mutations have been identified in the PAH gene
 * Molecular diagnosis for these mutations is possible but is only available on a limited clinical basis in the US and Canada
 * Mutations are identified and confirmed by DNA analysis using various methods
 * When mutation analysis is not available or disease-causing mutations are not identified in a family, linkage analysis can be considered for couples who have a child affected with PAH deficiency
 * No other phenotypes are known to be associated with mutations in the PAH gene

Determination of carrier status

 * Molecular testing used to be offered only to at-risk family members with a positive history
 * Now molecular testing can be offered to unrelated spouses and detects carriers with a rate of 98%
 * Not recommended for population screening to detect carriers
 * Three methods can be used
 * analysis of the plasma phe concentration and phe/tyr ratio (this test must take into account circadian variation and variations in a woman's menstrual cycle; it is not accurate during pregnancy.) When these variations are taken into account there is a 0.01 probability or less of heterozygote misclassification
 * DNA analysis if the disease-causing PAH mutation in the family is known
 * Linkage analysis with markers in the PAH gene

Prenatal Testing

 * Prenatal testing (once the genotype of the proband has been established) is possible for fetuses at 25% risk for PAH deficiency by amnio and CVS
 * Has also been done with linkage studies

Addenda
THE REST OF THE OUTLINE IS ONLY IF QUESTIONS ARISE, but much of it will be talked about by other members of the team

Symptoms/prognosis

 * Each person with PKU is affected differently and at varying levels of severity
 * Appear to have some other factors that may modify the phenotype (modifier genes and definitely environment)
 * Variations in severity correlate somewhat with the type of over 500 mutations in the phenylalanine hydroxylase gene located at chromosomal locus 12q22-q24
 * If diet is adhered to intelligence is usually in normal range, but still tends to be slightly lower than expected based on sibling and parent IQ's, but it mostly tends to correlate with levels of phe that are maintained and age at which treatment begun
 * Untreated patients often have:
 * abnormal electroencephalograms (EEGs)
 * seizures
 * neurologic disorders
 * a musty odor
 * varying degrees of mental retardation
 * Other possible symptoms include:
 * increased occurrences of eczema
 * tremor in the hands and eyelids
 * memory problems
 * raised levels of anxiety and depression
 * social disorders, i.e. agoraphobia
 * decreased motor functions, i.e. hand-eye coordination
 * on average, a loss of one IQ point per year off diet
 * Behavior problems of untreated or late-treated patients with PKU include:
 * Hyperactivity
 * aggressiveness
 * negative moods
 * motor and attention disturbances
 * self-inflicted injury

Screening

 * carried out in every state in the US and in many other countries with a heel-prick blood test
 * screening started in the mid-1960's however this could be earlier or later depending on which state and hospital
 * Utah statewide screening for PKU began in 1965 and galactosemia screening was added in 1979
 * PKU detected in virtually 100% of cases
 * Used to be done with Guthrie test that detected the presence of high phe by whether or not bacteria that were auxotrophic for phe would grow
 * Utah uses the Delphia method which is a fluormetric assay and is semi-quantitative
 * Mass spectrometry is now being used by some states (better accuracy and less false positives then Guthrie test)
 * In the US there are several hundred babies diagnosed and put on diet each year
 * An initial positive test does not necessarily mean that the child will have PKU
 * A false positive elevated phe concentration (hyperphenylalaninemia) may result from:
 * a blood spot that is too thick (when using Guthrie test)
 * a sample that is improperly prepared
 * combinations of the following: liver immaturity, protein overload (in newborns who are fed cow's milk), and heterozygosity for phenylalanine hydroxylase deficiency.
 * A second screening will be performed if the first is failed
 * If the second test is positive, than further quantitative testing will be performed to confirm the levels of phe
 * After hyperphe has been established, further tests must be done to distinguish those infants with PAH deficiency from the ~2% of infants with hyperphenylalaninemia who have impaired tetrahydrobiopterin (BH4) synthesis or recycling)
 * After diagnosis, the infant is treated without delay

Diet for PKU

 * Medical management is a low phe diet maintained throughout life
 * Just the right amount of phe is required because some is necessary for the body to make proteins
 * Adults with PKU who were not diagnosed at birth and have suffered irreversible brain damage can still benefit significantly from being placed on a phenylalanine-restricted diet (improved behavior noted)
 * not a typical vegetarian or vegan diet
 * protein replaced by low phe formula, usually taken in powdered form mixed with water
 * excludes all meat, fish, poultry, dairy, eggs, legumes chickpeas), nuts and seeds
 * diet includes starchy foods, fruits, vegetables, special low-protein products, and foods that contain no protein
 * starchy foods in the PKU diet contribute enough phenylanine
 * diet sweeteners such as Nutrasweet®, Sweetmate®, Canderal®, or aspartame® are made from phenylalanine and aspartic acid and should be avoided
 * diet must be carefully monitored so that growth and nutritional status are unaffected and deficiency of phenylalanine or tyrosine is not created.
 * must be adjusted for growth, illness, activity, etc.

Treatment in infancy and childhood

 * A phe-restricted diet and a phe-free medical formula must be started as soon as possible after birth under the direction of a nutritionist
 * Intake of tyrosine and total amino acids must be monitored
 * Consumption of phe-free formula should be spread out evenly over the 24 hours of the day to minimize fluctuations in blood amino acid concentrations
 * avoid long periods of low blood phe concentration, which is also harmful to brain development
 * blood phe concentration should be monitored periodically to evaluate control
 * Recommendations for monitoring may vary, but levels should be maintained below 6 mg/dl according to NIH consensus
 * Levels are usually taken weekly or bi-weekly in infancy and less frequently as a child gets older

Treatment in adolescence and adulthood

 * Recommendations for treatment of adolescents and adults vary
 * In general, support for "diet therapy for life" is increasing
 * Adults who have abandoned the phe-restricted diet tend to have a reduced attention span, slow information processing abilities, and slow motor reaction time
 * They also develop changes in the frequency distribution of brain electrical activity, increased muscle tone and tremor, lowered bone mineral content and mental health disorders
 * Controversy remains over the plasma phe concentration to be achieved for patients older than 12 years of age
 * General consensus is that the closer the phe concentration is to the recommended normal value, the better is the individual's general state of well being

Treatment for patients with levels below that of classical PKU

 * Patients with non-PKU HPA who have plasma phe concentrations consistently below (10mg/dl) have been shown to not be at higher risk of developing intellectual, neurological, and neuropsychological impairment than individuals without PAH deficiency
 * Some specialists believe that dietary treatment is unnecessary for the individuals in this class
 * However, others debate the advisability of non-treatment and will treat if level is above 5-6mg/dl

Maternal PKU risks

 * fetus can be severely damaged in the womb before birth by the effects of the mother's high PHE levels
 * Blood PHE levels of a pregnant woman transferred at a 1:3 ratio to fetus
 * very possible to have normal, healthy children if the mother follows the low-phenylalanine diet strictly before conception and throughout the pregnancy
 * women with PAH deficiency who are planning a pregnancy should start a phe-restricted diet prior to conception and should maintain plasma phe concentrations between 2 to 6mg/dl (ideally over several months) before attempting conception, but the exact preferred level depends on the clinic. (At the U of U Nichola prefers that they are kept between 2-4 mg/dl)
 * after conception, they should be offered continuous nutritional guidance and weekly or bi-weekly measurement of plasma phe concentration because dietary phe and protein requirements change considerably during pregnancy
 * the likelihood that the fetus will have congenital heart disease, intrauterine and post-natal growth retardation, microcephaly, and mental retardation depends upon the severity of the maternal HPA and the effectiveness of her dietary restriction
 * Potential consequences to the fetus if diet is not maintained
 * mental retardation
 * slowness in learning ability and growth
 * affect on short term memory
 * low birth size
 * microcephaly
 * congenital heart disease

Resources and References

 * Children's PKU Network
 * 1520 State St., Suite 111
 * San Diego, CA 92101-2930
 * Phone: (619) 233-3202
 * Fax: (619) 233 0838
 * Email: pkunetwork@aol.com

 * National PKU News
 * Virginia Schuett, editor/dietician
 * 6869 Woodlawn Avenue NE #116
 * Seattle, Washington 98115-5469
 * Phone: (206) 525-8140
 * Fax: (206) 525-5023
 * Email: schuett@pkunews.org
 * URL: http://www.pkunews.org

 * National Food Distribution Center
 * Roman Bhattacharya, Manager
 * 995 Wellington, Suite 220
 * Montreal, Quebec, Canada H3C 1V3
 * Email: roman@nfdc.info
 * URL: http://www.nfdc.info

 * Association for Neuro-Metabolic Disorders (ANMD)
 * PO Box 0202/L3220 Women's
 * 1500 Medical Center Drive
 * Ann Arbor, MI 48109-0202
 * Phone: 313-763-4697 (clinic)
 * Fax: 313-764-7502 (clinic)

 * Children's PKU Network
 * 1520 State St, Suite 111
 * San Diego, CA 92101-2930
 * Phone: 619-233-3202
 * Fax: 619-233-0838
 * Email: pkunetwork@aol.com

 * NCBI Genes and Disease Webpage
 * Web: www.ncbi.nlm.nih.gov/disease/Phenylketo.html

 * PAH/PKU Knowledgebase
 * Web: www.mcgill.ca/pahdb

 * Phenylketonuria: screening and management. NIH Consensus Statement 2000 Oct 16-18;17(3):1-27 [3394 references]
 * http://www.pkuadults.com/PKU information targeted to adults with PKU
 * www.pkunews.org National PKU News
 * http://www.yourgenesyourhealth.org/ygyh/mason/ygyh.html?syndrome=pku website with patient information and animation, quite detailed
 * gene clinics at www.geneclinics.org


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Handbook of Genetic Counseling/Pierre Robin Sequence - Cleft Palate

Pierre Robin Sequence - Cleft Palate

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Etiology

 * Primary defect - hypoplasia/ retrognathia of the mandibular area
 * Prior to 9th week of embryologic development
 * Tongue is then posteriorly located
 * Palatal shelves can not close properly
 * Posterior region must grow over the tongue to midline
 * Results in U-shaped cleft

Mode of inheritance

 * Most cases are sporadic
 * Familial cases have been reported
 * X-linked and AD modes have also been suggested

Incidence

 * 1:30,000 live births
 * Recurrence risk of CP: 3-5 % (jumps to 10-15% of 2nd child born with cleft)

Clinical Features
(Classic Triad = micrognathia, CP & glossoptosis)
 * Micrognathia
 * Cleft Palate (U-shaped)
 * Glossoptosis/ Macroglossia
 * Tongues falls backward and downwards
 * Airway obstruction
 * Feeding problems
 * May also have:
 * Ocular abnormalities (esotropia, congenital glaucoma)
 * Cardiac anomalies (ASD, PDA, VSD)
 * Some ear and skeletal defects have been reported

Natural history and life span

 * 30% mortality
 * Prognosis good if they survive the respiratory issues
 * Small jaw usually grows out during first two years
 * Chromic ear infections may cause conductive hearing loss

Testing

 * Prenatal diagnosis:
 * Not yet reliable
 * Level II ultrasound at 18-20 weeks

Surveillance, management and treatment options

 * Airway obstruction
 * Affected children should be monitored closely hypoxia and apnea
 * Nurse children in the prone position
 * Surgery to improve breathing (glossopexy or tracheostomy)
 * Cleft Palate
 * Feeding: use soft nipple with wide opening or squeeze bottle
 * Surgery to repair cleft (9-18 mos)
 * Ear infections: PE tubes
 * Work up should include: genetics consult, ophthalmologic eval, hearing eval, ENT eval, speech tx, and orthodontic eval

Differential diagnoses

 * Associated with numerous syndromes
 * trisomy 18
 * feeble cry, polyhydramnios with small placenta, renal and cardiac abnormalities, short palbebral fissures
 * Stickler syndrome
 * Up to 30% - 40%
 * Includes micrognathia, maxillary hypoplasia, epicanthal folds, depressed nasal bridge, hypotonia, hyperextensible joints, myopia, cataracts, retinal detachment
 * VCFS
 * Up to 15%
 * Cryptorchidism
 * Includes small mouth and mandible, overlapping 3rd and 5th digits, hypoplasia of nails, scissoring of limbs

Support groups, financial and educational resources

 * Pierre Robin Network (www.pierrerobin.org) - internet support group of parents
 * Wide Smiles, Inc. (www.widesmiles.org) - lots of info for parents
 * The Cleft Palate Foundation (CPF) (www.cleftline.org) or 1-800-24-CLEFT (24 hrs)

Psychosocial Assessment

 * How is BCMH working for you? And Early Intervention?
 * Any problems managing pt's care?
 * Nursing at home?
 * How have you been coping?
 * Do you have any support/ family in the area?


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Handbook of Genetic Counseling/Pituitary Tumor

Pituitary Tumor

Introduction

 * Acknowledge prior contact and receipt of family history information
 * Assess the most important concerns since there are so many issues at hand
 * Discuss family plans (timing, size, etc.) and how those plans may be influenced by what is learned today

Intake and Family History

 * Review family history information and personal health information already obtained
 * Use pedigree to make the review easier
 * Specifically ask about cancer in the family
 * Ask about pituitary tumor
 * When was it diagnosed? How? By whom?
 * What symptoms was she having?
 * Did she receive any treatment beside the drug mentioned?
 * Was surgery or radiation therapy ever discussed?
 * Has her physician discussed recurrence risks with her?

What is the Pituitary Gland?

 * The pituitary gland is a small, bean-shaped gland located in the center of the brain just above the back of the nose
 * The pituitary gland makes hormones that affect the growth and functions of other glands in the body; therefore it is sometimes called the "master gland"
 * Some hormones produced by the pituitary include: Thyroid Stimulating Hormone, Growth Hormone, Adrenocorticotropic Hormone, Luteinizing and Follicle Stimulating Hormones, Vasopressin, and others
 * When there is an abnormality of the pituitary gland, it often produces either too much or too little of one or a combination of hormones. This can result in a variety of hormonal problems that can affect the whole body.
 * Enlargement of the gland can also cause visual disturbances and/or impairment

Pituitary Tumors

 * Pituitary tumors or adenomas are almost always benign which means that they grow slowly and do not spread to other parts of the body
 * Pituitary tumors are rare.
 * Some may be "silent" lesions that are incidentally found at autopsy
 * The manifestations of a pituitary tumor depend on the hormones secreted by the tumor and the pattern of growth
 * Some hormonally active tumors are those that produce adrenocorticotropic hormone (ACTH), prolactin, or growth-hormone
 * Hormonally-inactive adenomas are often larger and may exhibit invasive properties. Thus, the likelihood for blindness is greater in patients with this tumor type
 * Pituitary tumors are seen in one of the multiple endocrine neoplasia (MEN) syndromes. MEN type I is well recognized, dominantly inherited, and comprises tumors of the parathyroid, pancreas and pituitary. Eighty percent of patients have involvement of 2 or more glands, and pituitary tumors occur in 54% to 80% of patients with MEN I.
 * MRI most readily determines the presence of a pituitary tumor, although it may also be established by CT (computer tomography) scan.
 * Many patients experience visual loss. Headaches occur in about 20%.

Treatment

 * Treatment depends upon the type of tumor and if it extends into the brain around the pituitary.
 * Hormone-secreting tumors may be treated with surgery or radiation therapy. Drug therapy with bromocriptine has been used with success in patients with prolactin-secreting tumors.
 * Lesions that extend beyond the confines of the pituitary often require radiation therapy and surgery

Risk for

 * I could not find a population rate for pituitary tumors, only that they are "very rare"
 * sister was probably treated with bromocriptine which was used in the past for lactation cessation and is currently used to treat prolactin-secreting pituitary tumors
 * Her tumor was likely small at the start, and she has responded well to treatment thus far
 * Even if sister has a recurrence of the tumor, it will not affect the risk that this couple would have a child with a pituitary tumor


text:
Handbook of Genetic Counseling/Polycystic Kidney Disease

Polycystic Kidney Disease

Introduction

 * Greet the family/parent
 * What do you understand about why you are here in genetics today?
 * What questions or concerns do you want to have addressed today?

Elicit Medical History
(interim history form)
 * update medical history since last seen
 * determine if there have been any problems since released from the hospital
 * assess developmental history

Update Family History

 * Update pedigree
 * determine if there are any other family members with kidney problems, heart problems, liver problems or that died in early infancy

What is Polycystic Kidney Disease (PKD)?

 * Two main types
 * Autosomal Dominant PKD (adult PKD)
 * Autosomal Recessive PKD (infantile PKD)

ADPKD
symptoms usually develop beginning in early adulthood although can be found in the infant period or not begin until later in adulthood
 * Etiology and Natural History
 * gene PKD1 mutated in about 85% of cases
 * gene PKD2 mutated in about 15% of cases
 * large amount of variability both within and between families
 * Prevalence and Inheritance
 * most common single gene disorder that is potentially lethal
 * prevalence at birth: 1/400 - 1/1000
 * 10% of cases due to new mutation
 * occurs in all races
 * inherited in autosomal dominant fashion
 * if one parent is affected there is a 50% chance of having an affected child
 * Symptoms
 * multiple bilateral renal cysts (100% of cases)
 * leads to end stage renal insufficiency by 60 years old in 50% of cases
 * cysts in other organs specifically the liver (20% by 3rd decade; 75% by 6th decade)
 * intracranial aneurysms (10% of cases)
 * more common in patients with family history of intracranial aneurysms (22%) than those without this history (6%)
 * mitral valve prolapse and other heart defects
 * Diagnosis
 * patients with known 50% risk
 * at least 2 cysts either unilateral or bilateral by 30years of age
 * large kidneys without cysts in infants and children
 * patients with no known risk
 * bilateral renal enlargements and cysts
 * in absence of indication for different renal cystic disease
 * suggestive of ADPKD, but not definite diagnosis
 * Differential from:
 * ARPKD - unaffected parents
 * Glomerulocystic kidney disease - minimal tubular involvement
 * Molecular Testing
 * Linkage analysis - need a large number of family members to establish which gene is responsible
 * Prenatal Testing - only available after a mutation has been identified in an affected family member
 * Management
 * no treatment for disease itself
 * treat symptoms to prevent premature death and alleviate pain

ARPKD

 * Etiology and Natural History
 * mutation in PKHD1 locus (6p21) present in all studied patients with ARPKD
 * enlarged echogenic kidneys found in perinatal period
 * large amount of variability both within and between families
 * 30% of patients with ARPKD die in neonatal period
 * Prevalence and Inheritance
 * prevalence: 1/20,000 - 1/40,000
 * prevalence may be underestimated due to death in neonatal period
 * carrier frequency: 1/70
 * inherited in autosomal recessive fashion
 * if both parents are carriers there is a 25% chance of having a child who is affected, 50% chance of having a child who is a carrier, and a 25% chance of having
 * Symptoms
 * enlarged, echogenic kidneys with poor differentiation (100% of cases)
 * renal function impaired in 70-80% of cases
 * hypertension
 * usually occurs within first week of life
 * Liver disease (45% of cases at presentation)
 * pulmonary hypoplasia resulting from oligohydramnios
 * other abnormalities: low set ears, micrognathia, flattened nose, growth deficiency
 * Diagnosis
 * enlarged echogenic kidneys with poor differentiation
 * one or more of the following:
 * absence of renal cysts in parents
 * signs of hepatic fibrosis
 * pathoanatomical proof of ARPKD in affected sibling
 * parental consanguinity suggesting AR inheritance
 * Differential from:
 * ADPKD - more likely to have bilateral macrocysts
 * Glomerulocystic kidney disease - minimal tubular involvement
 * Molecular Testing
 * Linkage analysis - based on accurate diagnosis of ARPKD in affected individual and accurate understanding of relationships in family
 * Prenatal Testing - only available after a linkage has been identified in an affected family member
 * Management
 * no treatment for disease itself
 * treat symptoms to prevent premature death and alleviate pain
 * stabilize respiratory function
 * feeding difficulty and growth failure in children

Psychosocial Issues

 * uncertainty of diagnosis and prognosis may lead to anxiety
 * possibity that parent could find out they have the diease (for ADPKD)
 * guilt over passing trait to child
 * Concern for risks to future pregnancies
 * Are you interested in pursuing linkage analysis?
 * How are you dealing with your son's health problems?
 * Are you anxious about the possibility of upcoming surgeries?
 * Reassure that this could not have been prevented

Recommended Follow-up for PKD

 * renal ultrasounds to monitor cysts and function
 * control of hypertension
 * CT scan to detect aneurysm (ADPKD)
 * monitor liver function

Resources

 * PKD foundation (www.pkdcure.com)


text:
Handbook of Genetic Counseling/Polydactyly and Syndactyly

Polydactyly and Syndactyly

Medical and Family History

 * Medical history
 * How/when did they diagnose the polydactyly/syndactyly?
 * Is it bilateral?
 * Has she had X-rays or other imaging? Is this scheduled?
 * Pregnancy history - teratogen exposures, illness, womb anomalies
 * Birth history - any complications?
 * Hearing screen? Responses to sound?
 * Family history
 * Polydactyly/syndactyly? Other limb anomalies?
 * Cleft lip or palate?
 * Learning difficulties? Mental retardation?
 * Heart defects? Kidney abnormalities?
 * Skeletal abnormalities? Short stature? Other birth defects?

Overview of Hand/Foot Abnormalities

 * Presence of more than normal number of fingers or toes
 * Can vary from rudimentary finger or toe to fully developed extra digits
 * Syndactyly
 * Webbing or fusing of two or more fingers or toes
 * Varies from incomplete webbing of skin of two digits to complete funtion of digits or fusion of bones and nails
 * Fusion can be connected by shared skin, bones, nerves, vessels, or nails
 * Polysyndactyly is presence of extra digits that are fused
 * Fetal development of digits
 * Limbs arise from small limb buds
 * Upper limb bud appears 26-27 days after fertilization, lower limb bud 28-30 days
 * Consists of mesenchymal core covered by epithelial tissue
 * Apical ectodermal ridge (AER) forms along anteroposterior surface
 * Longitudinal growth of limb with pattern forming proximodistally and anteroposteriorly
 * Homeobox genes and morphogen (possibly retinoic acid) provide information for cell growth and division
 * Separation of digits occurs due to programmed cell death in interdigital zones
 * Anything that disrupts patterning or programmed cell death can result in limb defect

Syndactylies

 * Most are malformations except when associated with amniotic bands
 * Can be classified based on anatomic criteria
 * Syndactyly type I
 * Cutaneous syndactyly of fingers 3 and 4 or toes 2 and 3
 * Can be bilateral in hands (50%) and feet (66%)
 * Syndactyly of toes is four times more common than fingers
 * Can be inherited as autosomal dominant trait
 * About twice as common in males than in females
 * Syndactyly type II (synpolydactyly)
 * Syndactyly of fingers 3 and 4 or toes 4 and 5 with partial or complete duplication of digit
 * Can be variable, hand anomalies can be severe including clinodactyly
 * Extra digit may have fused, forked, or broad metacarpals and metatarsals, complete or partial duplications or digit
 * Incidence is uncertain, some autosomal dominant forms have been reported
 * Syndactyly type III
 * Variable cutaneous or osseous syndactyly of fingers 3 to 5
 * Syndactyly might be complete or partial, nails may be fused
 * Condition is rare
 * Syndactyly type IV (Haas type polysyndactyly)
 * Complete cutaneous syndactyly of fingers and/or thumbs with a degree of polydactyly on radiography and a hypoplastic or triphalangeal thumb
 * Hands often resemble "mitten" deformity
 * Rarely seen as isolated defect, very rare with few families reported
 * Syndactyly type V
 * Metacarpal and metatarsal fusion associated with variable degrees of syndactyly
 * Usually involves digits 4 and 5 but can be variable
 * Can be variable involvement within families
 * Autosomal dominant and X-linked recessive families have been described
 * Rare - only 10 families reported
 * Complete syndactyly
 * Includes digits 2-5 and may include thumb also
 * Usually seen with Apert syndrome (craniosynostosis)
 * Cenani-Lenz syndrome
 * Syndactyly involving all elements of all digits, often with fusion of radius and ulna or tibia and fibula
 * Hands and feet often appear as mass of digits
 * Autosomal recessive inheritance
 * Preaxial syndactyly
 * Failure of separation of preaxial digits of hands and feet
 * Postaxial digits are relatively normal
 * Lack of separation of thumb from finger 2 in hands, similar in feet
 * Only reported in one family
 * Symbrachydactyly
 * Shortening of phalanges and other elements of digits in association with cutaneous syndactyly
 * Usually seen unilaterally, middle phalanges tend to be more severely affected
 * Incidence estimated to be 1/32,000

Polydactylies

 * Usually manifest as extra digits or incomplete digits resulting in broad or bifid digit
 * Postaxial polydactyly (80% of cases)
 * Extra digit on ulnar or fibular side of limb
 * Type A postaxial polydactyly
 * Digit usually consists of three phalanges and nail
 * Extra digit is relatively well formed but some or all of elements may be reduced
 * Type B postaxial polydactyly
 * Extra digit is represented by small conical projection or tag containing distal phalanx and nail on fifth digit
 * 10 times more common in African-Americans than Caucasians
 * Unilateral in 2/3 of cases, affects left side twice as commonly as right
 * Autosomal dominant inheritance with reduced penetrance
 * Preaxial polydactyly
 * Preaxial polydactyly type I
 * Complete or partial duplication of a normal biphalangeal thumb
 * Varies from extra phalanx to complete hypoplastic thumb
 * May cause broadening of distal phalanx to triphalangeal thumb
 * More common in males, most often unilateral, usually not familial
 * Part of many malformation syndromes
 * Preaxial polydactyly type II (triphalangeal thumb)
 * Opposable thumb with three phalanges
 * Estimated incidence is 1/25,000
 * Usually sporadic, associated with prenatal hydantoin and thalidomide exposure, can be autosomal dominant
 * Preaxial polydactyly type III (polydactyly of an index finger)
 * Duplication of the index finger with or without an additional biphalangeal or triphalangeal thumb
 * Can be autosomal dominant or associated with genetic syndromes
 * Preaxial polydactyly type IV (polysyndactyly)
 * Duplication of preaxial digits associated with syndactyly of the extra rays
 * May see broadening of thumbs or six or seven toes
 * Autosomal dominant with complete penetrance
 * Sporadic cases occur in 1/10,000 births
 * Mirror hands and feet
 * Polydactyly of hand or foot with appearance of mirror duplication around midline axis of arm or leg in absence of recognizable thumb or great toe
 * Very rare with a few autosomal dominant cases but usually sporadic

Treatment/Management Options

 * Diagnosed by external observation, X-ray, or ultrasound
 * Polydactyly
 * Can be corrected surgically to improve appearance and functioning
 * Usually done at 1 year of age so skeletal development is complete and accurate anatomic assessment can be done
 * May require reconstruction of any associated abnormalities in remaining digit
 * Cast and soft dressing may be used until healed
 * Syndactyly
 * Treatment aimed at maintaining and improving function with cosmetic benefits
 * Involves surgery and may require skin graft from groin area
 * Surgery usually done after 1 year and may be delayed as late as 18-24 months

Resources

 * MUMS parent to parent matching
 * Phone: 1-877-336-5333
 * Email: mums@netnet.net
 * Web:www.netnet.net/mums/

 * Penn State Health and Disease Information
 * Web: www.hmc.psu.edu/healthinfo/pq/poly.htm

 * Specific resources and support groups available for genetic conditions


text:
Talk:Guide to Social Activity/Body Language

Body language is, more generally, not specific to Courtship. Improvements needed to this module: --Kernigh 01:54, 9 December 2005 (UTC)
 * Expanded scope - not only gender neutrality, but the meanings of body language outside the limited idea of courtship/dating.
 * Verifiability - this module appears to contain some speculations, and it is necessary to have a way to check them. A good way to start establishing this would be to create links to Wikipedia articles.

The how-to in this module might to too passive. Sometimes it suggests to let the other person do something, when you could do it. For example, in the current version, instead of letting the other person observe your rapport, you could observe the rapport of the other person. --Kernigh 19:02, 12 February 2006 (UTC)

I am the origional author of http://www.seductionreport.com and grant copyright permission to Wikibooks--Seductionreport.com 08:18, 16 April 2006 (UTC)

The above link to "seduction report" is dead. Azotochtli (discuss • contribs) 17:54, 15 July 2012 (UTC)


text:
Handbook of Genetic Counseling/Prader-Willi Syndrome - Prenatal

Prader-Willi Syndrome - Prenatal

Introduction

 * Discuss the reason for referral.
 * Elicit prior knowledge about Prader-Willi syndrome.
 * Elicit prior knowledge about prenatal diagnosis.
 * Assess concerns and set goals for the session.
 * Provide overview of topics for counseling session.

Client & Partner Information

 * Discuss why it's important to get pregnancy, personal, and family history.
 * Explain that it is a way to identify other potential risk factors
 * Use examples: seizure medication, diabetes, etc.
 * Go over pregnancy history:
 * How has the pregnancy been going?
 * G1P1? Any stillbirths? Spontaneous or elective abortions?
 * Was the pregnancy planned? If so, how long did it take to become pregnant?
 * LMP? EDC?
 * Any bleeding?
 * Any illnesses during the pregnancy?
 * Infection, cold, rash, fever?
 * Any chronic illnesses?
 * Any exposures during the pregnancy?
 * X-rays, smoking, alcohol, recreational drugs?
 * Medications:
 * Currently?
 * Earlier in the pregnancy?
 * Personal background:
 * Occupation?
 * Do you have a religious preference?
 * Psychosocial assessment
 * Financial, insurance concerns?
 * Support system?
 * Information about the father:
 * Name, age, occupation?
 * Any exposures?
 * Any chronic illnesses?

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 Prader-Willi Syndrome?

 * A complex, multi-system mental retardation disorder
 * The first recognized microdeletion syndrome identified when high-resolution chromosome analysis was introduced
 * Now known to be one of the most common microdeletion syndromes
 * Also one of the most common recognized genetic forms of obesity
 * Caused by several different genetic alterations of proximal chromosome 15q

Etiology & Incidence

 * History
 * Prader-Willi syndrome was first described in 1956.
 * The basis of Prader-Willi syndrome
 * Caused by the lack of expression of normally active paternally inherited genes at chromosome 15q11-q13
 * The maternally inherited genes are normally inactive due to genetic imprinting
 * Imprinting is a phenomenon by which some genes are modified in different ways depending on the genederof the parent from whom they were inherited
 * There are 3 ways in which P-W syndrome can be caused.
 * Small deletion in the paternally contributed chromosome 15
 * This is seen in 75% of patients
 * Usually the deletion is 4-Mb or smaller
 * Uniparental disomy 15 (UPD)
 * Inheritance of 2 maternal chromomes 15 but no paternal chromosome 15
 * Defect in the imprinting process
 * Seen in approximately 1% of patients
 * Very small deletion or other abnormality in the imprinting center
 * All studied families in which there has been a recurrence of P-W have had an imprinting mutation.
 * The actual genes whose deficiency that cause the phenotype have not yet been identified
 * One-third of patients with P-W exhibit hypopigmentation due to deletion of a gene associated with tyrosinase-positive albinism
 * Incidence
 * 1 in 10,000 - 15,000
 * Occurs in both sexes and all races
 * Diagnosis is often delayed or missed in many cases

Clinical Features & Natural History

 * Neonatal hypotonia and failure to thrive
 * Hypotonia is prenatal in onset and nearly uniformly present
 * Causes decreased fetal movement, frequent abnormal fetal position, and difficulty at time of delivery
 * State of hypoarousal are associated with poor suck and lack of awakening to feed
 * Hypotonia gradually improves
 * Motor milestones are delayed
 * Average age of sitting is 12 months
 * Average age of walking is 24 months
 * It is recommended that all newborns with persistent hypotonia be tested for P-W
 * Developmental delay and mild cognitive impairment
 * Language development is delayed
 * Speech is often poorly articulated, having a nasal and/or slurred character
 * Most patients are mildly retarded
 * Mean IQ 60s to low 70s
 * Approximately 40% have borderline retardation or low normal intelligence
 * 20% have moderate retardation
 * Characteristic facial appearance
 * Narrow bifrontal diameter
 * Almond-shaped palpebral fissures
 * Narrow nasal bridge
 * Downturned mouth with a thin upper lip
 * Early-childhood-onset obesity
 * Hyperphagia begins generally between ages 2 and 4 leading to significant obesity
 * Hypothalamic abnormality results in lack of satiety
 * There is a decreased caloric requirement likely related to hypotonia and decreased activity
 * Food seeking behavior with hoarding or faraging for food and stealing food or money to buy food are common
 * High threshold for vomiting may complicate binging on spoiled food
 * The obesity is central in distribution, with relative sparing of the distal extremities
 * Obesity is the major cause of morbidity and mortality in P-W syndrome
 * Hypogonadism with genital hypoplasia
 * Hypogonadism is prenatal in onset and persists throughout life
 * Genital hypoplasia is evident at birth
 * Pubertal development is abnormal
 * In both males and females, sexual activity is uncommon and fertility is rare
 * Mild short stature
 * If not apparent in childhood, it is almost always present by the second half of the second decade
 * Average height is 155cm for males and 148cm for females
 * African-Americans tend to be taller
 * Characteristic behavior profile
 * Becomes evident in early childhood
 * Tempor tantrums, stubbornness, controlling and manipulative behavior
 * Obsessive-compulsive characteristics
 * Difficulty with change in routing
 * Lying, stealing, and aggressive behavior
 * True psychosis is evident in young adulthood in approximately 5-10%
 * Sleep disturbances
 * Excessive daytime sleepiness and oxygen desaturation in REM sleep
 * These are common even in the absence of obesity

Inheritance

 * P-W is caused by a lack of expression of the paternally derived PWS/AS region of chromosome 15q11-q13 by one of several genetic mechanisms
 * Deletion of PWS/AS region
 * 70% of patients have P-W syndrome by this genetic mechanism
 * <1% risk to siblings of an affected proband
 * Most of these cases are de novo deletions
 * A small number of cases are due to translocation with a concomitant deltion
 * If a parent has a balanced chromosomal translocation the recurrence risk could be as high as 25%
 * Uniparental disomy
 * 25% of patients have P-W syndrome by this genetic mechanism
 * <1% risk to siblings of an affected proband
 * Imprinting defect
 * <5% of patients have P-W syndrome by this genetic mechanism
 * The risk to siblings of an affected proband is up to 50%
 * A healthy parent can carry this imprinting defect
 * But recurrence risk may be lower because imprinting defects can be de novo mutations
 * Balanced chromosome translocation within 15q11-q13 or abnormality
 * <1% of patients have P-W syndrome by this genetic mechanism
 * All of these cases have been de novo
 * Risk to siblings of an affected proband is <1%
 * If a familial case is detected, the theoretical risk of inheritance of the balanced translocation could be as high as 25%

Diagnosis

 * Genetic testing
 * Molecular Genetic Testing
 * Testing for the parent-specific methylation imprint detects over 99% of cases and is highly specific
 * Methylation-specific testing is important to confirm the diagnosis in all children
 * The methylation abnormality can be determined by southern blot hybridization using a methylation-sensitive probe (SNRPN or PW71B) or with parent-specific PCR primers
 * If the methylation pattern is characteristic of maternal inheritance only, then the diagnosis is confirmed
 * DNA methylation testing detects all cases caused by deletions, UPD, and imprinting defects
 * Once the diagnosis is established, further tests are done to classify the mutation
 * Deletions can be detected using FISH analysis
 * UPD can be detected with informative microsatellite markers
 * An imprinting defect is presumed to be present in patients with an abnormality in the parent-specific methylation imprint without evidence of a deletion or UPD
 * Cytogenetic Analysis
 * 1% of patients have a detected chromosomal rearrangement resulting in a deletion of bands 15q11-q13
 * Deletion can be detected using high resolution chromosome studies at the 650 band level and FISH.
 * Clinical diagnosis
 * Consensus diagnostic criteria were developed in 1993
 * Major Criteria
 * Neonatal and infantile hypotonia with poor suck
 * Feeding problems and/or FTT in infancy
 * Onset of rapid weight gain between 1-6 years of age causing central obesity
 * Hyperphagia
 * Characteristic facial features
 * Hypogonadism
 * Genital hypoplasia
 * Incomplete and delayed puberty
 * Infertility
 * Developmental delay or mild to moderate MR or multiple learning disabilities
 * Minor Criteria
 * Decreased fetal movement and infantile lethargy
 * Typical behavior problems
 * Sleep disturbance/sleep apnea
 * Short stature for the family by 15 years of age
 * Hypopigmentation
 * Small hands and feed for height age
 * Narrow hands with straight ulnar border
 * Esotropia, myopia
 * Thick, viscous saliva
 * Speech articulation defects
 * Skin picking
 * Supportive Findings
 * High pain threshold
 * Decreased vomiting
 * Scoliosis and/or kyphosis
 * Early adrenarche
 * Osteoporosis
 * Unusual skill with jigsaw puzzles
 * Normal neuromuscular studies such as muscle biopsy

Differential Diagnosis

 * Hypotonia in infancy
 * Neonatal sepsis
 * CNS depression
 * Congenital myotonic dystrophy
 * Several myopathies and neuropathies
 * Developmental delay/mental retardation, obesity, and hypogonadism
 * Albright hereditary osteodystrophy
 * Bardet-Biedl syndrome
 * Cohen syndrome
 * Borjeson-Forssman-Lehmann syndrome
 * Some patients with Fragile X syndrome
 * Possible 6q or 1p deletions

Management

 * Infancy
 * Special feeding techniques, including special nipples or gavage feeding to assure adequate nutrition
 * Physical therapy may improve muscle strength and encourage achievement of milestones
 * Screening for strabismus should start in infancy
 * Childhood
 * Obesity
 * Monitoring of weight and nutritional counseling are critical
 * Low-calorie, well-balanced diet with regular exercise and close supervision to minimize food stealing should be instituted before the onset of excessive weight gain
 * Energy requirement should rarely exceed 1000 to 1200 Kcal/day
 * Learning disabilities should be evaluated, and educational planning instigated
 * Speech therapy is often needed
 * Growth hormone replacement
 * Normalizes height and increases lean body mass
 * Growth hormone evaluation is recommended if growth rate is reduced or height is less than the 3rd percentile
 * Behavioral disturbances
 * Often follow excessive weight gain
 * Firm limit-setting should be instituted
 * Serotonin re-uptake inhibitors have helped many patients with managing behavior
 * Sex hormone replacement is controversial
 * Produces adequate secondary sexual characteristics
 * Testosterone replacement may play a role in male behavior problems
 * Estrogen replacement may increase risk of stroke and osteoporosis in females
 * Scoliosis screening should be routine
 * Adulthood
 * Obesity
 * The major cause of morbidity and mortality in adults
 * Can cause medical complications
 * Cardiopulmonary compromise
 * Type II diabetes mellitus
 * Thrombophlebitis
 * Chronic edema
 * If obesity is avoided, longevity may be nearly normal
 * Psychiatric and behavioral disturbances may require hospitalization and medication
 * Psychosis
 * Manic-depressive illness
 * Obsessive-compulsive disorder
 * Group homes specifically designated for patients with P-W have been successful

Psychosocial Issues

 * Uncertainty because symptoms and severity vary widely
 * Uncertainly may make goal-setting and future planning problematic
 * Feelings of isolation, loneliness, and despair.
 * Frustration due to ignorance about the disease.
 * Coping with chronic pain and fatigue
 * Burden of dealing with a chronic, rare, progressive disease
 * Body image and self-esteem issues due to spleen or liver enlargement or growth retardation
 * Guilt about passing on the gene to one's children.
 * Family dynamic changes
 * Stress in the marriage
 * Sibling relationships
 * Family members may feel guilty or resentful
 * Depression and frustration about the requirement for lifelong management.
 * Shock, fear, and denial over the diagnosis.

Offer Resources
1-888-MODIMES
 * Prader-Willi Syndrome Association
 * (800) 926-4797
 * www.pwsausa.org
 * The Prader-Willi Foundation
 * (800) 253-7993
 * PWSAUSA@aol.com
 * March of Dimes information on Spina Bifida, Amniocentesis, Folic Acid, and Maternal blood screening
 * www.modimes.org


text:
Handbook of Genetic Counseling/Spina Bifida

Spina Bifida

Quote Risks

 * Spina bifida is usually an isolated birth defect.

Level II Ultrasound

 * At 18-20 weeks, a high resolution, targeted ultrasound examination can be done to carefully and specifically examine the baby's spine.
 * This is noninvasive and may provide reassurance but cannot be used as a diagnostic tool.
 * If no evidence of a NTD is seen, it cannot be guaranteed that the baby does not have a NTD.

Amniocentesis

 * If the triple screen results indicate an increased risk for a NTD, one may choose to have an amniocentesis, which is a more invasive, but more diagnostic test.
 * 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
 * What can it tell me?
 * Amnio can detect certain abnormalities in the fetus.
 * Chromosome abnormalities
 * NTDs (Spina Bifida)
 * It can determine the sex of the baby.
 * What can it NOT tell me?
 * Amnio 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 amnio.
 * 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.
 * The first few cc's of fluid will be discarded because they probably contain contamination from your cells.
 * 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.
 * There is a small possibility of lab error or lack of cell growth
 * In this case, the procedure would have to be done again.
 * What will it feel like?
 * If an anesthetic is used, you may not feel the needle enter the skin, but you will still feel it enter the uterus.
 * This is described as a sharp pain, like a menstrual cramp that usually lasts a few seconds.
 * You may also feel some cramping after the procedure.
 * You should avoid strenuous activity for 24 hours after the procedure.
 * Call your doctor immediately if you experience abdominal pain or cramps, vaginal bleeding, leakage of clear fluid from the vagina, fever, or anything else unusual.
 * Approximately 2% of women experience light bleeding or spotting.
 * 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.

Other Resources

 * Spina Bifida Association of America
 * SBAA
 * 1-800-621-3142

Review and summarize major points
www.sbhac.ca spina bifida association of Canada

Reporting of the Results

 * If they are having a procedure, discuss how they would like to receive the results
 * Appointment, phone call, etc.
 * Who will contact them?
 * Discuss the options: elective abortion, adoption, etc.


text:
Handbook of Genetic Counseling/Chorionic Villus Sampling (CVS)

Chorionic Villus Sampling (CVS)

Introduction

 * Discuss the reason for referral.
 * Elicit prior knowledge about CVS.
 * Elicit knowledge about AMA or other indications for session.
 * Assess concerns and set goals for the session.
 * Provide overview of topics for counseling session.

Client & Partner Information

 * Discuss why it's important to get pregnancy, personal, and family history.
 * Go over pregnancy history:
 * G?P?
 * LMP? EDC?
 * Infertility?
 * Exposures?
 * Medical complications?
 * How has the pregnancy been going?
 * Personal background:
 * Occupation?
 * Religion?
 * Ethnicity?
 * Chronic illness?
 * Partner exposure?

Elicit Family History

 * Construct pedigree:
 * Abnormal # miscarriages, stillbirths, infant deaths?
 * Previous children with chromosome abnormality, NTD, Down syndrome, birth defects, mental retardation?
 * Consanguinity?
 * 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.
 * The age of 35 is the "magic" number because this is when the risk of the procedure is justified.
 * The background risk for major birth defects for women of all ages is 3-5%.

Explain Chromosome Abnormalities

 * Explain cells, chromosome, and DNA
 * Show karyotypes
 * Explain nondisjunction
 * Show abnormal karyotypes (trisomy 13, 18, 21, sex chromosome anomalies)
 * 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.

Quote Risks

 * Show charts to figure risk of chromosome abnormalities.
 * Give age-specific risks:
 * Age at CVS: ____________
 * Down syndrome: 1 in _______ ( %)
 * Any CA: 1 in ________ ( %)

Discuss the option of CVS

 * What is it?
 * CVS is short for chorionic villus sampling
 * 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
 * The technique has been around for approximately 15 years although methods have changed over time
 * 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 tell me?
 * CVS can detect certain abnormalities in the fetus
 * General chromosome abnormalities
 * Specific genetic disorders that have been previously identified
 * It can determine the sex of the baby.
 * 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
 * A speculum is inserted and the vagina and cervix are cleaned with betadeine
 * Some physicians apply a tenaculum to the lip of the cervix which can be painful
 * Using US to guide, a thin tube is guided into the placenta
 * Gentle suction is applied to the tube to remove the villi
 * This method is easiest to perform when the placenta is posterior and close to the cervix
 * A larger sample is taken as compared to transvaginal CVS
 * Discomfort is often minimal, perhaps similar to a pap smear
 * Post-procedure bleeding occurs in up to 10% of patients
 * Transabdominal CVS:
 * Done at 10 weeks gestation or later
 * The abdomen is cleansed with betadeine
 * A local anesthetic injection may be given
 * 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
 * This method is easiest when the placenta is anterior or away from the cervix
 * This method is better for women with a retroverted uterus
 * A smaller sample (pieces of villi) is taken as compared to transcervical CVS
 * The procedure is usually more uncomfortable than the transcervical method
 * Bleeding after the procedure is rare
 * 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 will it feel like?
 * There may be some discomfort when the needle enters the skin and the uterus or when the catheter enters the cervix and placenta
 * Some say that they feel pressure during the procedure
 * You may experience a small amount of bleeding after CVS
 * 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
 * CVS increases the risk of miscarriage by 5/100 (5%) in women with a retroverted uterus using transcervical CVS
 * 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%)
 * There are special considerations for mothers who are Rh negative. They need to take RhoGam after the CVS procedure
 * There is a low risk of uterine infection
 * Exercise or strenuous activity is to be avoided for 24 hours after the procedure
 * Sexual intercourse, douching, tub baths, or tampon use are to be avoided for 72 hours after CVS procedure
 * CVS is not recommended for women with the following:
 * Cervical polyps, overly curved sampling pathway, active genital herpes (for trans-cer)
 * Interceding bowel, placenta too far from abdomen surface (for trans-abd)
 * Active vaginal bleeding or bleeding disorder
 * You should notify your doctor if any of the following occur:
 * Fever greater than 100.4 F
 * Heavy bleeding or cramping
 * Amniotic fluid leakage
 * Why should I choose CVS?
 * CVS can be done earlier than amniocentesis (10-12 weeks versus 15-18 weeks)
 * It may reduce a couples emotional stress if at risk for abnormality
 * The procedure allows for termination at an earlier age
 * This is before the pregnancy is visible
 * Also before fetal movement is felt
 * Allows for treatment of fetus affected with 21-hydroxylase deficiency
 * Why might I not want to choose CVS?
 * There is a higher risk for pregnancy loss as compared to amniocentesis
 * 1% for CVS versus 0.5% for amnio
 * CVS does not detect NTDs
 * CVS is less commonly done as compared to amnio
 * With CVS, there is a greater likelihood of needing further invasive testing due to:
 * Laboratory failure
 * Insufficient sample
 * Maternal cell contamination
 * Seen in approximately 1.9% of cases
 * Mosaic or ambiguous results
 * There are 2 or more cell types that are different genetically
 * Seen in 1-2% of CVS cases

Offer Resources

 * Literature, contact info, etc.
 * March of Dimes website

Reporting of the Results

 * If they are having the procedure, discuss how they would like to receive the results
 * Appointment, phone call, etc.
 * Who will contact them?
 * Discuss the options: elective abortion, adoption, etc.