Term
| Duchenne Muscular Dystrophy |
|
Definition
X-linked, deletion of dystrophin gene, 1 in 3500
A fatal, progressive degeneration of muscle from hip/shoulder girdle out that appears before the age of 4 years survive to age 17/18. Gower's maneuver
Affects voluntary muscles as well as heart and breathing muscles, most die of pneumonia or decline in pulmonary function. Most (95%) have cardiac abnormalities. Chronic heart failure develops in 50% of pts
Calf hypertrophy, hyperlordosis, decreased tendon reflexes.
Over 90% afflicted boys chair-bound by age 11
Moderate intellectual compromise
Significant mental retardation in 20% of pts
Elevated serum creatinine kinase >50 x normal
Therapy objectives: slow disease progression, maintain mobility, prevent contractures and scoliosis, weight control, optimize cardiopulmonary function.
Mother-to-son: 50% risk for each son and each daughter to inherit mutation
Daughters have a low risk of developing DMD, but 50 to 60% chance of developing cardiac abnormalities
Even non-carrier mother has a 7% risk of having a boy with DMD
PTC124 Trial Now Open to Boys With DuchenneMuscular Dystrophy Who Have Nonsense Mutations (15%)
Nonsense mutations (premature stop codon) prematurely end the synthesis of a protein —in this case dystrophin—leading to a small, nonfunctional protein that can't perform its cellular role |
|
|
Term
Familial Adenomatous Polyposis
"Gardner's syndrome" |
|
Definition
Autosomal dominant, mutation of APC gene. 2-3/100,000 accounts for 1% of colon cancer. APC may occur in 80% of sporadic colorectal tumors. Chromosome 5 can usually be evaluated, but 20% are not detected.
100-1,000 of polyps (<.1-2 in.) form, onset teens/young adults, polyps usually adenomatous(benign) by age 40 often become cancerous.
APC mutation also causes dysplasia: benign tumors in skin, soft connective tissue, and bones
Symptoms: usually none in early disease stage-screening is key
blood in stool, diarrhea, constipation, crampy abdominal pain, change in bowel habits, persistent decrease in size of stool, abdominal distention, weight loss.
Exam Guidelines: start at 7 and every year after, 25-24 every other year, 35-50 every 3 years, over 50 every 3-5 years.
Management: early recognition, total colectomy, surveillance, genetic testing. |
|
|
Term
|
Definition
Hereditary 20%-exact gene is known for
APCI1307K mutation, FAP, Peutz- Jegher, HNPCC, Juvenile Polyposis
Sporadic 80%
Familial 15%-50% - someone in your family had it too. Gene unknown |
|
|
Term
|
Definition
Milder form of FAP, fewer, unevenly distributed polyps, develop cancer at later age.
Need colonoscopy rather than sigmoidoscopy. Screening should begin at age 11 |
|
|
Term
|
Definition
Autosomal dominant, prevalence 1/200 to 1/1000 in caucasian pop. 5% of hyperlipidemia cases. Panethnic.
Homozygous-present w/atherosclerotic disease in childhood, die from MI <30, very high levels of LDL(8x) and total cholesterol(600-1200 mg/dL)
Heterozygous-present in 30s/40s, LDL 2x normal,cholesterol elevated(350 mg/dL), 80% develop xanthomas.100% risk of developing CHD by age 70(male),75% if female.
LDL-receptor mutation affects metabolism of cholesterol and lipids. Chromosome 19 codes for LDL receptors.
Acculmulation of LDL form occlusive arterial plaques(atheromas) and papules of lipid-laden macrophages(xanthomas) sign of abnormal levels of lipids.
phenotypic features: hypercholesterolemia (earliest finding), atherosclerosis, xanthomas, corneal arcus (last two appear in 2nd decade of life).
Corneal arcus-bilateral gray, white, or yellow deposits, found at <40 years of age severe risk, need to be evaluated.
6 types
Management-rule out 2ndary causes, dietary modifications:add omega 3s, lower sat. fat, calories, and cholesterol, stop smoking.
Meds-only when pt. is not responding to above. HMG-CoA reductase inhibitors or statins like Lipitor, Zocor(simvastatin), and Crestor, Niacin(nictinic acid) decreases hepatic LDL and VLDL, may cause flushing, and WelChol(colesevelam) binds intestinal bile acids. |
|
|
Term
|
Definition
Collection of fat, cholesterol, and other substances in arterial walls.
Larger called plaques or atheromas.
Consequences-
Calcification increases rigidity of vessle wall
Plaque rupture leads to thrombosis
Hemorrhage into plaque narrows the lumen
Fragmentation leads to emboli
Weakening of vessel wall leads to aneurysm. Atherscerotic disease is most common cause of abdominal aortic aneurysm. |
|
|
Term
| Hereditary Nonpolyposis Colon Cancer |
|
Definition
Autosomal dominant, five genes are known to cause HNPCC called hMSH2(30%), hPMS1(rare), MSH6(rare)(all on chromosome 2), hMLH1 (chromosome 3-30%), and hPMS2 (chromosome 7-rare). 30% Unknown.
Microsatellite Instability (MSI) and
Immunohistochemistry (IHC) Testing-
used to find which gene mutation is present.
Positive genetic testing should have colonoscopy every year, prophylactic surgery possible.
Phenotypic Features: age of onset: middle adulthood, colorectal cancers, multiple primary cancers.
Clinical features:
•Early but variable age at CRC diagnosis (~ 45 years)
•Tumor site in proximal colon predominates, right side.
•Extracoloniccancers including endometrial, ovary, stomach, urinary tract, small bowel, bile ducts, and sebaceous skin tumors.
Amsterdam Criteria:
Three or more relatives with verified CRC in family
One case a first-degree relative of the other two
Two or more generations
One CRC by age 50 FAP excluded
Failure to meet these criteria does not exclude HNPCC.
Symptoms:none in 1st stages,
blood in stool, diarrhea, constipation, crampy abdominal pain, change in bowel habits, persistent decrease in size/caliber of stool, abdominal distention, weight loss for no known reason.
Exam:
•Colonoscopy every 1-2 years starting by age 20-25 years or 5 to 10 years before the age of earliest colorectal cancer diagnosed in the family, whichever is younger. At age 40 begin annual colonoscopy.
•For women: yearly pelvic exam with Pap test, transvaginalultrasound of the uterus and ovaries starting at age 25 and continuing annually
•Consider annual upper endoscopy in families with gastric cancer.
Dx: confirmed by barium enema, colonoscopy/sigmoid.
Tx: removal of any polyps, colectomy or proctocolectomy. |
|
|
Term
|
Definition
•Hereditary: genetically transmitted from parent to offspring
•Familial: occurring in or affecting more members of a family than would be expected by chance |
|
|
Term
|
Definition
Automsomal dominant disorder of connective tissue characterized by abnormalities in organs-heart(aorta), skeleton, eyes, and skin. 30% sporadic cases, affects 2/10,000. ~200,000 effected people in U.S. Most common single-gene malformation.
Gene FBN1(chromosome 15) encodes fibrillin-a protein necessary in formation of microfibrils.
Microfibrils-structural support for tissues such as aortic adventitia, ciliary zonules, and skin.
Onset:early childhood, untreated leads to premature death, median age of survival w/treatment 74(F) and 70(M).
No cure. Surveillance, prevention, and managing symptoms to slow disease progression.
Phenotypic features:
disproportionate tall stature lower body longer than upper body and arachnodactyly, slender habitus, ectopia lentis-dislocation of lens, severe nearsightness(myopia), mitral valve prolapse,aortic dilatation or rupture, spontaneous pneumothorax, scoliosis. |
|
|
Term
|
Definition
| A genotype that determins a phenotype similar to that determined by a different genotype. |
|
|
Term
|
Definition
Autosomal recessive,in U.S. 80,000 have SCD(1/500 A.Americans)(1/1000 Hispanics) 2 million have the trait(1/12 A.Americans).
Normal:HgB Sickle Cell:HgS
Missense mutation causes amino acid substitution (valinine replaces guanine) and leads to decreased solubility of deoxygenated Hgb. Hgb polymerizes causing RBC deformity.
Sickle cells occlude capillaries causing infarction and necrosis. Life of cell is diminshed to 10-20 days.
Anemia is caused by lack of healthy RBCs.
Signs and symptoms:
Anemia
Crises-episodes of pain due to blockage by sickle-shaped RBC
Hand-foot syndrome-swollen hands and feet often 1st sign in babies.
Jaundice –liver overwhelmed by rapid breakdown of RBC
Frequent infections –sickle cells can damage spleen
Stunted growth-lack of oxygen and nutrients, vision problems.
Complications:blindness, organ damage, CVA, leg ulcers, gallstones-high bilirubin from RBC breakdown, priapism, Acute chest syndrome:chest pain, fever, dysapnea, caused by lung infection or trapped sRBC in lungs. Tx:antibiotics, blood transfusion, and bronchdilators.
Tx:
Bone marrow transplant-potential cure.
Otherwise aimed at preventing crises:
antibiotics, pain meds, blood transfusions(poss. iron toxicity), supplemental oxygen, hydroxyurea-stimulates fetal Hgb preventing sickle formation, long-term use leads to tumors or leukemia.
Experimental Tx: gene therapy, butyric acid-increase fetal Hgb, clotrimazole-prevents water loss from RBC reduce sickled cells, nitric oxide-dilates blood vessles and reduces stickiness/may prevent sickle formation. |
|
|
Term
| Sickle Cell Trait versus Sickle Cell Disease |
|
Definition
Sickle cell trait
��Have one gene for the disease
��No signs and symptoms
��Don’t develop the disease unless exposed to low oxygen
��Approximately 1 in 12 black Americans
��Protected against malaria.
Sickle cell disease
��Have two genes for the disease
��Show signs and symptoms after 4 months of age
��Some people have mild symptoms
��Others have severe symptoms and need frequent hospitalization |
|
|
Term
|
Definition
A pathological deficiency in the oxygen-carrying component of the blood, measured in unit volume concentrations of hemoglobin, red blood cell volume, or red blood cell number.
Lab Values:
��Hemoglobin (Hgb)
Male = 14 –18 g/100 mL
Female = 12 –16 g/100 mL
��Hematocrit(Hct)
Male = 40 –54%
Female = 37 –48%
��Mean corpuscular volume (MCV)
86 –98 μm3/cell |
|
|
Term
|
Definition
|
|
Term
|
Definition
Trisomy 21, aneuploidy
A disorder that includes a combination of birth defects-severity varies greatly among individuals
One of the most common genetic birth defects. Affects ~ 1 in 800 to 1000 babies.
Life expectancy among adults is ~ 55 years
Heart defects –~ 50%
Intestinal malformations –~ 10%
Visual or hearing impairment –> 50%
Amblyopia, near-or far-sightedness, cataracts
Frequent colds and otitismedia
Increased risk for thyroid problems and leukemia
Fewer than 10% have severe mental retardation.
Small, folding ears; small mouth, small nose and flattened bridge; eyes may slant, short necks, small hand/short fingers, short stature.
Risk factors: mothers age >35, parents who already have had a Down's baby,recent studies suggest abnormal folic acid metabolism of mother.
80% women under 35 have Down's babies
Men with Down syndrome cannot father a child (rare exceptions)
A woman with Down syndrome has 50/50 chance of conceiving a Down child
Many affected fetuses miscarry
Substantial number of adults (15 to 20%) develop Alzheimer’s disease in middle age
Nuchaltranslucency measurement
��First trimester ultrasound exam that involves measuring subcutaneous fluid-filled space at the back of the fetal neck
��Performed between 11 and 13 weeks
��Increased measurement = Down syndrome |
|
|
Term
|
Definition
|
|
Term
|
Definition
Amniocentesis
��A technique in which a sample of amniotic fluid is removed and cells that it contains are grown on a culture dish
��Cannot be done until the 14th to 16th week of pregnancy
��The risk of inducing a spontaneous abortion by this procedure is 0.5 to 1% above the background rate of spontaneous abortion
ChorionicVillusSampling
��A small amount of the placenta is removed
��Normally done during the 10th to 12th week but it can be done as early as the 5th week of pregnancy.
Karyotypeanalysis can be performed on these cells immediately after sampling
��Although chorionicvillus sampling can be performed earlier in the pregnancy than amniocentesis, the risk of inducing a spontaneous abortion is 1 to 2% higher than the background rate.
Maternal serum screening
��Includes alpha fetoprotein (AFP), human chorionicgonadotropin(hCG), and unconjugatedestriol(uE3)
��Blood obtained between 15 and 18 weeks of gestation
��Results provide information about risk of Down syndrome, neural tube defects (i.e., spinabifida), and trisomy18
��Low AFP, low uE3, and high hCGassociated with increased risk of Down syndrome |
|
|
Term
|
Definition
2nd most common trisomy after trisomy 21.
Severe psychomotor and growth retardation, microcephaly, microphthalmia, malformed ears plus other deformities.
Characteristics: clenched hand and rocker bottom feet. |
|
|
Term
|
Definition
XXY, 1942 Klinefelter found signs-1959 discovered the extra chromosome. Cause: random event-nondisjunction
Effects males only
AKA Testicular Dysgenesis
Most common chromosomal disorder associated with male hypogonadism and infertility.
Most males go through life without being diagnosed. Diagnosis, when made, usually occurs in adulthood due to hypogonadism and infertility. About 40% of concepti with KF survive the fetal period.
Phenotypic abnormalities, including mental retardation, directly related to number of extra X chromosomes.
Intelligence quotient (IQ) reduced by ~ 15 points for each extra X chromosome.
Characteristics:
Small, firm testicles, Small penis, Sparse pubic, axillae, and facial hair, Sexual problems, Gynecomastia, Tall stature, Abnormal body proportions, and Long legs, short trunk.
Lab studies:
Cytogenetic studies
Hormone profile
High plasma FSH, LH, and estradiollevels
Low plasma testosterone levels
Low semen count
Echocardiography to detect mitral valve prolapse
Treatment: address hypogonadism w/ testosterone replacement beginning at puberty, gynecomastia w/ plastic surgery, and psychosocial problems w/ specific counseling.
Risk of breast cancer is 20x higher for these men, mitralvalve prolapsein 55% of patients, varicose veins occur in 20 to 40% of pts.
Slight increase in acute leukemia, Hodgkin and non-Hodgkin lymphomas, CML, and gonadaltumors. |
|
|
