Genetics

Question 1

M:F 1:1 affected, male to male transmission, parents affected

Answer 1

Autosomal Dominant

1. 50% chance of affected child from affected parent.
2. only one abnormal copy of gene to have phenotype
3. structural genes, transcription factor genes
4. No carrier state

Question 2

more than one affected child without affected parents, recessive like pedigree

Answer 2

Suspect gonosomal Mosaicism of Autosomal Dominant disorder

Question 3

NF 1 diagnostic criteria

Answer 3

1. > 6 cafe-au-lait spots (>5mm prepubertal) or (>15mm postpubertal)
2. Two or more neurofibromas
3. two or more Lisch nodules of the iris
4. Inguinal or axillary freckling
5. optic pathway tumor
6. osseous lesions: sphenoid wing dysplasia/thinning of long bone cortex
7. First degree relative with NF1

Question 4

ortic root dilatation, risk of aortic rupture, MVP, uppward lense dislocation, myopia, tall stature, abn upper to lower body ratio, pectus deformity, scoliosis, arachinodactly, Spinal dural ectasia

Answer 4

Marafan Syndrome,
Fibrillin on chr15
Marfan2 and loey-Dietz Syndromes caused by mutationsin TGF beta receptor 1 and 2

Question 5

M:F 1:1 parents may not be affected, skipped generation

Answer 5

Autosomal Recessive

1. 25% chance of having affected child with EACH pregnancy
2. Mutations typically in genes for enzymes
3. look for consanguinity
4. Need two copies of abnormal genes

Question 6

Coarse facies, corneal clouding, organomegaly, cognitive loss, (difficulty straightening the hand)

Answer 6

Hurler Syndrome
lysosomal storage disorder
(mucopolysaccaridoses); mutation in alpha-1 iduronidase gene

Question 7

persistent elevation of phe level

Answer 7

Phenylketonuria (PKU)
1 in 12,000 new borns,
mutation in phenylalanine hydroxlase gene

Question 8

Males affected, criss cross inheritance

Answer 8

X linked recessive

Females are carriers

Question 9

progressive symmetric myopathy, proximal>distal, calf hypertrophy, symtoms start prior to 5 years of age, cannot walk by age 13

Answer 9

Duchenne Muscular Dystrophy, dystropin gene on Xp, carrier females may develop cardiomyopathy,

Question 10

Lab findings in Duchenne

Answer 10

1. CK 10 times normal value
2. Muscle biopsy - fiber size variation, necrosis, minimal dystropin staining
3. DNA testing - 65% deletion 30%point mutation

Question 11

coarse facies, hump on the back, gibbous, cognitive loss, organomegaly, short stature, CLEAR cornea

Answer 11

Hunter syndrome

lysosomal storage disorder (mucopolysaccaridosis)

Question 12

Affected females with h/o miscarriages (boys)

Answer 12

X linked Dominant, lionization may impact phenotype,

Males have severe or lethal phenotype

Question 13

Cognitive delay, hand wringing, breath holding, seizures, progressive neurologic, mostly seen in girls

Answer 13

Rhett syndrome,
MECP2 at Xq28
atypicall rhett may present as Autism

Question 14

inheritance through maternal lineage, almost all offsprings affected, disorders of energy metabolism, lactic acidosis

Answer 14

Mitochondrial gene mutation/inheritance

severity of disease depend on % of abnormal mitochondria,

Question 15

lactic acidosis, myopathy with ragged red fibers, dilated or hypertrophic cardiomyopathy

Answer 15

Mitochondrial myopathy and Cardiomyopathy

gene coding tRNAs in mitochondrial genome

Question 16

no clear pattern of inheritance, genetic liability and environment,

Answer 16

multifactorial inheritance
eg: cleft lip/palate, neural tube defects, CHD
Recurrence risk ~ 5%

Question 17

hand/foot edema, neck webbing, wide carrying angle, low hair line, wide spaced nipples, short stature, HEARING LOSS,

Answer 17

Turner Syndrome, 5/1000
1. Horse shoe/ectopic kidney,
2. hypothyroidism, infertility, amenorhea
3. CHD - coarct, bicuspid aortic valve, hypoplastic left heart, VSD, ASD, APVR
4. HTN, increased risk of aortic dissection in pregnancy
Abnormal X chromosome dosage.