Mendelian Inheritance

Question 1

Achondroplasia

Answer 1

• Autosomal Dominant Inheritance
• Most common skeletal dysplasia
• Tyrion Lanister (Game of Thrones!)
• Gonadal Mosaicism

Question 2

Variable Expressivity

Answer 2

• Features of a disorder may vary between affected individuals, even in the same family (Marfan Syndrome)
• Occurs in autosomal dominant inheritance

Question 3

Marfan Syndrome

Answer 3

• Variable Expressivity
• Systemic disorder of connective tissue
• Ocular, Skeletal (Bone overgrowth and joint laxity), and cardiovascular systems
• Source of Mortality: Dilatation of the aorta–> rupture

Question 4

Autosomal Dominant inheritance

Answer 4

• Variable expressivity
• Incomplete penetrance
• New (de novo) mutations– increases w/ advancing age!

Question 5

Incomplete Penetrance

Answer 5

Not all individuals with a mutation have phenotypic effects (i.e. BRCA gene mutations)

Question 6

Cystic Fibrosis

Answer 6

• Autosomal Recessive Inheritance
• Multisystem disease: primarily in pulmonary and digestive systems
• 95% males are infertile

Question 7

Autosomal Recessive Inheritance

Answer 7

• 2 mutated copies of gene needed for trait expression
• Not gender specific
• Consanguinity may be present
• Ethnic predisposition may be noted (Sickle Cell Anemia)
• Less clinical variability
• Penetrance is usually complete

Question 8

Sickle Cell Anemia

Answer 8

• Autosomal Recessive Inheritance
• Ethnic Predisposition
• Intermitent pain crises, organ damage (vaso-occlusion) and chronic hemolytic anemia

Question 9

Hemophilia

Answer 9

X-linked Recessive

• Bleeding Disorder (Mostly internally, into the joints or muscles)
• Deficiency in Factor VIII or IX

Question 10

X-Linked Recessive Inheritance

Answer 10

• Males are more likely to be affected than females
• No male to male transmission
• Multiple generations may be affected
• All daughters of affected male are carriers
• “Carrier” females may show mild expression of trait

Question 11

Duchenne Muscular Dystrophy

Answer 11

X-linked recessive inheritance

• “Skewed” X-inactivation
• Progressive disease of skeletal muscle
• Usually presents in early childhood

Question 12

Incontinentia Pigmenti

Answer 12

X-linked Dominant Inheritnance

• Disorder of skin, hair, teeth, nails, eyes, and central nervous system
• Cognitive delays/intellectual disability are occasionally seen
• Rare

Question 13

X-Linked Dominant Inheritance

Answer 13

• Females are much more likely to be affected
• Often lethal in males
• All daughters of affected male are affected
• No male to male transmission
• Less common than X-linked recessive