Genetic Diseases

Question 1

Achondroplasia

Answer 1

• AD
• FGFR3, Impaired endochondral ossification.
• Most common dwarf, normal size head
• Increased with increasing paternal age

Question 2

ADPKD

Answer 2

• Cystic dilation and renal failure in 30-50s
• Renal failure, HTN, hematuria
• Cysts in liver, increased risk cricle of willis anyerism, mitral prolapse

Question 3

Hyperchol IIa

Answer 3

• AD defect in LDLR
• Homozygous early lethal with tendonous xanthomas
• Heterozygous is premature cardiovascular disease

Question 4

Spherocytosis

Answer 4

• AD
• Ankyrn or spectrin
• Extravascular hemolysis from splenic macrophages. Splenectomy is currative
• Increased MCHC

Question 5

CF

Answer 5

AR
Most commonly causes misfolded protein that is degraded in ER
Thick mucus
-Treated with N acetylcysteine to break up disulfide bonds

Question 6

Muscular Dystrophies

Answer 6

XR

• Duchene: Frameshift mutation in dystrophin which links cytoskeleton to ECM.
• Becker is less severe and presents in teenage years

Question 7

Trinucleotide repeats

Answer 7

• Problem with methylation (???)
• Fragile X: Retard etc, also mitral valve prolapse
• Huntingtons: Decrease GABA and Ach
• Freidrich
• Myotonic Dystrophy

Question 8

Downs Syndrome

Answer 8

Trisomy 21, caused by meotic nondisjunction most of the time. Can also rarely be caused by robertsonian translocation of chrom 21 onto another chrom.

• Increased risk with increasing maternal age
• Quad test will show decreased AFP, increased HCG, decreased estriol, increased inhibin A. Increased Nuchal Translucency
• Associated with ASD (Ostium Primum), Hirschprung, duodenal atresia, alzheimers, ALL.

Question 9

Edwards

Answer 9

• Trisomy 18, same reasons as downs
• Retardation, rocker bottom feet, usually die by age 1. Clentched fists.
• Decreased AFP, HCG, Estriol, normal inhibin A

Question 10

Patau

Answer 10

• Trisomy 13
• Holoprosencephaly, cleft lip and palate, rocker bottom feet
• Decrease HCG, PAPP-a. Increased Nuchal Rigidity

Question 11

Cri-Du-Chat

Answer 11

• Deletion of long arm chromosome 5

- Cry of cat, microcephaly, retardation, VSD

Question 12

WIlliams

Answer 12

• Deletion long arm 7 (contains elastin)

- Elf facies, normal verbal and very friendly to strangers, Hyprcalcemia

Question 13

22q11 deletion

Answer 13

• Di George like diseases. Failure of 3rd and 4th pharyngeal arches to develop correctly
• Thymic, PTH, Cardiac Defects (tetrology of fallot), also commonly have cleft palate