Autosomal Dominant Disorders

Question 0

What is the autosomal dominant disorder where deletion of NF1 gene at 17q11.2 causes RAS-GTP lock in “on” position?

Answer 0

Neurofibromatosis Type 1

Question 1

What are characteristics of an autosomal dominant disorder?

Answer 1

• No skipped generations
• males and females equally effected
• 25% AA (severely affected), 50% Aa (affected), 25% aa (unaffected)
• some with variable expressively and penetrance may see reduced penetrance
• 50:50 recurrence risk for children born to affected individual
• new mutations common due to germ line mutations in >35 fathers

Question 2

What autosomal dominant disorder has a recurrent risk of 1/3500?

Answer 2

Neurofibromatosis Type 1

Question 3

What autosomal dominant disorder has the following phenotype:

• Cafe-au-lait spots
• axillary/inguinal freckling
• neurofibromas (benign tumors of the cell sheaths around PNS nerves)
• Lisch nodules (iris hemartomas)
• bony lesions
• increased risk of gioblastomas, pheochromocytomas, and myelogenous leukemias
• could progress to neurofibrosarcomas

Answer 3

Neurofibromatosis Type 1

Question 4

What autosomal dominant disorder has the following treatments/diagnosis:
- genetic family testing usually not done because symptoms are specific

Answer 4

Neurofibromatosis Type 1

Question 5

What autosomal dominant disorder is 100% penetrant, highly variable expressivity, new mutations account for 50% of all cases?

Answer 5

Neurofibromatosis Type 1

Question 6

What autosomal dominant disorder is the result of FBN1 gene affecting the fibrillin protein?

Answer 6

Marfan’s Syndrome

Question 7

What autosomal dominant disorder has a 1/5000 to 1/10,000 recurrence risk?

Answer 7

Marfan’s Syndrome

Question 8

The following phenotype is characteristic of what autosomal dominant disorder:
Ectopia Lentes, dilated aortic root, dural ectasia, at least four of the following skeletal changes: pectus carinatum, pectus excavatum, wrist and thumb signs, scoliosis of >20%, reduced extension at the elbows, protrusio acetabulae, arm span to height ratio >1.05

Answer 8

Marfan’s Syndrome

Question 9

What autosomal dominant disorder is highly penetrant, rare germ line mosaicism, 25% de novo

Answer 9

Marfan’s Syndrome

Question 10

What autosomal dominant disorder has an LDL (low density lipoprotein) receptor mutation?

Answer 10

Familial Hypercholesterolemia

Question 11

What autosomal dominant disorder has a recurrence risk of 1/500?

Answer 11

Familial hypercholesterolemia

Question 12

What dominant autosomal disorder has the following phenotype:
- atherosclerosis (M1/stroke), skin xanthomas

Answer 12

Familial hypercholesterolemia

Question 13

What autosomal dominant disorder can be diagnosed using a serum LDL test?

Answer 13

Familial hypercholesterolemia

Question 14

In what autosomal dominant disorder are tests to determine difference in affected genes are not done unless the cholesterol level is at ~2,000

Answer 14

Familial hypercholesterolemia

Question 15

In what autosomal dominant disorder does FGFR3 activation of function mutation= inhibition of bone growth, 98% of mutations are G1138A

Answer 15

Achondroplasia

Question 16

What autosomal dominant disorder has a recurrence risk of 1/15,000 to 1/40,000?

Answer 16

Achondroplasia

Question 17

What autosomal dominant disorder has the following phenotype:
- short stature, rhizomelic shortening of arms and legs, macrocephaly, and facial features with frontal bossing, normal IQ, CNS complications from small foramen magnum?

Answer 17

Achondroplasia

Question 18

What autosomal dominant disorder is a common form of short limbed dwarfism, 80% de novo- 100% from fathers germ line, homozygosity= lethal

Answer 18

Achondroplasia

Question 19

What are examples of autosomal dominant disorders?

Answer 19

Neurofibromatosis Type 1
Marfan’s Syndrome
Familial hypercholesterolemia
Achondroplasia