Genetic Disorders & Inborn Errors Of Metabolism Flashcards
Marfan syndrome is an autosomal ______ disorder
What gene defect is associated with Marfan syndrome?
Autosomal dominant
The gene defect has been mapped to a region on chromosome 15 that codes for fibrillin
What are the clinical features of Marfan syndrome?
Skeletal findings:
Occular findings:
Cardiovascular findings:
- Skeletal findings: tall stature with elongated extremities and long fingers, long narrow, face, hyper extension of joints, high arched narrow palate
- Occular findings: ectopia lentis, irdodonesis, upward lens subluxation
- Cardiovascular findings: Aortic regurgitation, mitrial valve prolapse, Aortic route dilatation (aneurysm)
What disorder has many of the same clinical features as Marfan’s syndrome and must be ruled out
Homocystinuria
What are some complications of marfan’s syndrome?
Endocarditis, retinal detachment, and sudden death as a result of aortic dissection
What are some clinical features of Prader-Willi syndrome?
crazy appitie and obesity
- Craniofacial: Almond-shaped eyes; fishlike mouth
- hypotonia, Failure to thrive;
- obesity as a result of hyperphagia later in childhood
- short stature, mental retardation, DD, behavior problems
- Hypogonadism
What is Noonan syndrome?
“male version of Turner syndrome”
What are the clinical features of Noonan syndrome?
- Short stature and a shield chest
- Short webbed neck and low hairline
- Right-sided heart lesions, most commonly pulmonary valve stenosis
- Mental retardation in 25%
What two distinct syndromes have a deletion at chromosome 22q11?
DiGeorge syndrome
Velocardiofacial syndrome
What is CATCH-22?
A name describing the features of 22q11 deletions
- Cardiac anomaly
- Abnormal facies
- Thymic hypoplasia
- Cleft palate
- Hypocalcemia
- Gene defect on chromosome 22
DiGeorge syndrome is caused by a defect in the structures derived from the ____ and _____ pharyngeal pouches
third and fourth
THymus and parathyroid hypoplasia in DiGeorge syndrome cause…
cell-mediated immunodeficiency and severe hypocalcemia
What is osteogenesis imperfecta?
Results from mutations that cause production of abnormal type I collagen
What are the clinical features of Type I Osteogenesis Imperfecta?
- Blue sclerae
- Skeletal findings such as fragile bones
- Yellow or gray-blue teeth
- Easy bruisability
Pierre Robin syndrome clinical features?
Micrognathia, cleft lip and palate, and a large protruding tongue
What is the most common trisomy syndrome?
Down syndrome (trisomy 21)
What is the second most common trisomy syndrome? It is three times more common in ________
Trisomy 18; females
________ is 20 times more common in Down Syndrome than in general population
Leukemia
How are trisomy syndromes diagnosed?
Chromosomal analysis
What are the clinical features of Turner syndrome?
XO — only female
- Short stature
- Webbed neck
- Shield chest
- Swelling of the dorsum of hands and feet
- pubertal delay - Ovarian dysgenisis
- lymphedema, low hairline, learning issues, low ears
- heart: bicuspid aorta, coar of aorta
- hearing loss and eye issues
What cardiac effects are associated with Turner syndrome?
- Left-sided heart lesions
- Coarcatation of the aorta
- Bicuspid aortic valve
- Hypoplastic left heart
Fragile X syndrome is an X-linked disorder caused by a site on the X chromosome that contains a variable number of ____ repeats
CGG
What type of inheritance pattern is associated with Fragile X syndrome?
inherited, no spontanous mutation
What is the most common inherited cause of mental retardation?
Fragile X syndrome
boys > girls because they only have one X
What are some clinical features of Fragile X syndrome?
- Mild to severe mental retardation
- Large ears
- Large testes develop during puberty
- Emotional instability
What is the most common cause of male hypogonadism and infertility?
Klinefelter syndrome (XXY)
What are the clinical features of Klinefelter syndrome?
Normal at birth and presents in puberty
- Tall stature with long extremities
- Hypogonadism (INFERTILITY)
- Gynecomastia
- Variable intelligence
- Antisocial behavior; excessive shyness or agression
What is the most common teratogen?
Alcohol
What are some features of fetal alcohol syndrome?
- Small-for-gestational age at birth
- FTT
- Microcephaly
- Long smooth philtrum with a thin, smooth upper lip
- Mental retardation, ADHD, and cardiac defects
Pick the IEM that goes with the following odors:
- Mousey/musty:
- Sweet maple syrup:
- Sweaty feet:
- Rotten cabbage:
- Mousey/musty: Phenylketonuria
- Sweet maple syrup: Maple syrup disease
- Sweaty feet: Isovaleric or glutaric acidemia
- Rotten cabbage: Hereditary tyrosinemia
Ammonia is toxic to the ____ and _____
brain and liver
What type of inheritance is associated with galactosemia? What enzyme is deficient?
Autosomal recessive
Galactose-1-phosphate uridyltransferase deficiency
Galactosemia should be suspected in any newborn with ________ and _______
hepatomegaly and hypoglycemia
What are some clinical features of galactosemia?
- Vomiting, diarrhea, and FTT
- Hepatic dysfunction with hepatomegaly
- Cataracts with oil-droplet appearance
- Renal tubular acidosis
Tay-Sachs disorder is an autosomal ______ disorder caused by ____________ deficiency
Recessive; hexosaminidase A
What are the clinical features of Tay Sach’s disease?
- normal at birth, decline at 3 to 6 months
- Hyperacusis (increases sensitivity to sound) –> spastic
- progressive hypotonia
- Macrocephaly
- Cherry red macula
- Progressive blindness, seizures
- Severe developmental delay
Ashkenazic Jew pop
Juvenile or adult-onset Tay sachs disease has the same clinical features as the infantile form except for…
cherry red macula
Infantile Tay-Sachs disease is untreatable and death occurs by ___ years
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