Genetic disorders

Question 1

ADPKD

Answer 1

• -Autosomal dominant
• -Bilateral enlargement of kidneys due to multiple cysts
• -Mutation of APKD1 on chromosome 16
• -Associated with berry aneurysms
• -Flank pain, hematuria, HTN, progressive renal failure

Question 2

Achondroplasia

Answer 2

• -Autosomal dominant
• -Defect of fibroblast growth factor receptor #3
• -Associated with advanced paternal age

Question 3

Familial Adenomatous Polyposis

Answer 3

• -Autosomal dominant
• -High risk of colon cancer
• -Mutation in APC gene

Question 4

Gardner Syndrome

Answer 4

• -Autosomal dominant
• -Osteomas
• -Lipomas
• -Sebaceous cysts
• -Colon polyps
• -Colon cancer

Question 5

Familial hypercholesterolemia

Answer 5

• -Autosomal dominant
• -Type IIA hyperlipidemia
• -Markedly elevated LDL
• -Xanthomas, xanthelasmas, early MI

Question 6

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

Answer 6

• -Autosomal dominant

- -Telangiectasias, recurrent epistaxis, skin discoloration, Arteriovenous malformations, GI tract bleeding

Question 7

Hereditary sperocytosis

Answer 7

• -Autosomal dominant
• -Spheroid erythrocytes
• -Defect of spectrin or ankyrin (provide structural framework of RBC)
• -Hemolysis leading to anemia and jaundice, increased MCHC
• -Positive osmotic fragility test
• -Increased viscosity of blood

Question 8

Huntington disease

Answer 8

• -Autosomal dominant
• -CAG repeats
• -Decreased GABA and Ach in brain
• -Cognitive decline, caudate atrophy, chorea, chromosome 4, average age 40

Question 9

Marfan syndrome

Answer 9

• -Autosomal dominant
• -Fibrillin gene mutation
• -Pectus excavatum, hyper-extensibile joints, long fingers and toes
• -Cystic medial necrosis of aorta, aortic valve regurgitation, aortic aneurysm, aortic dissection, mitral valve prolapse
• -Subluxation of lenses

Question 10

Multiple Endocrine Neoplasia

Answer 10

• -Autosomal dominant
• -MEN1 associated with MEN1 gene
• -MEN2A and 2B associated with RET gene mutation
• -MEN1: Parathyroid adenoma, pituitary adenoma, pancreatic tumors
• -MEN2A: Parathyroid adenoma, pheochromocytoma, medullary thyroid cancer
• -MEN2B: Pheochromocytoma, medullary thyroid cancer, mucosal neuromas

Question 11

Neurofibromatosis type 1

Answer 11

• -Autosomal dominant
• -Mutation of a gene on chromosome 17
• -Cafe-au-lait spots, neural tumors, Lisch nodules, scoliosis

Question 12

Neurofibromatosis type II

Answer 12

• -Autosomal dominant
• -Bilateral acoustic neuroma (CN VIII)
• -Hearing loss, tinnitus, balance problem
• -Mutation on chromosome 22

Question 13

Tuberous Sclerosis

Answer 13

• -Autosomal dominant
• -Mutation of hamartin or tuberin gene
• -Non-malignant tumors in the brain and other organs
• -Facial lesions, hypopigmented ash-leaf spots, cortical and retinal hamartomas
• -Seizures
• -Intellectual disability
• -Cardiac rhabdomyomas and astrocytomas

Question 14

von-Hippel-Lindau disease

Answer 14

• -Autosomal dominant
• -Hemangioblastomas of the retina, cerebellum, and medulla
• -50% develop bilateral renal cell carcinoma
• -Pheochromocytomas
• -Deletion of VHL gene on chromosome 3–> activation of angiogenic growth factors

Question 15

Li-Fraumeni syndrome

Answer 15

• -Autosomal dominant

- -Mutation in TP53–> multiple malignancies at early age.

Question 16

Fragile X syndrome

Answer 16

• -X-linked disorder, trinucleotide repeat disorder
• -Mutation with FMR1 gene which codes FMRP
• -Intellectual disability, macro-orchidism, long face, large jaw, everted ears, mitral valve prolapse
• -CGG repeat

Question 17

Trinucleotide repeat disorders

Answer 17

• -Fragile X syndrome (CGG)
• -Friedreich ataxia (GAA)
• -Huntington disease (CAG)
• -Myotonic dystrophy (CTC)

Question 18

Friedreich ataxia

Answer 18

• -Autosomal recessive, trinucleotide repeat disorder
• -Mutation of gene that codes for frataxin
• -Degeneration of sensory neurons, hypertrophic cardiomyopathy, diabetes mellitus
• -Staggering gait, frequent falling, nystagmus, dysarthria, pes cavus, and hammertoes
• Presents with childhood with kyphoscoliosis
• -Degeneration of spinocerebellar tracts, posterior columns, dorsal root ganglia

Question 19

Myotonic Dystrophy type 1

Answer 19

• -Autosomal dominant
• -CTG trinucleotide repeat expansion in the DMPK gene–> abnormal expression of myotonin protein kinase–> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia.

Question 20

Cystic fibrosis

Answer 20

• -Autosomal recessive
• -CFTR gene on chromosome 7 mutation
• -Thick mucus (because Cl- not moving properly and Na+ can’t and can’t follow)
• -Recurrent pulmonary infections, bronchiectasis, pancreatic insufficiency, meconium ileus, infertility in males, fat soluble vitamin deficiencies, salty taste
• -Diagnose with sweat chloride test
• -Rx: N-acytylcysteine, antibiotics, pancreatic enzymes, fat soluble vitamins

Question 21

X-linked recessive disorders

Answer 21

• -Ocular albinism
• -Fabry disease
• -Wiscott-Aldrich
• -G6PD deficiency
• -Hunter Syndrome
• -Bruton agammaglobulinemia
• -Hemophilia A/B
• -Lesch-Nyhan Syndrome
• -Duchenne muscular dystrophy