Some Genetic Diseases from First Aid Biochem

Question 1

Achondroplasia

Answer 1

autosomal dominant mutation in FGFR3 inhibits chondrocyte proliferation. Full penetrance.

Question 2

ADPKD

Answer 2

bilateral enlargement of kidneys due to cysts. 85% of cases are due to mutation in PKD1 (chromosome 16, 16 letters in “polycystic kidney”). Remainder due to PKD2. Autosomal dominant.

Question 3

FAP

Answer 3

familial adenomatous polyposis. colon becomes covered with adenomatous polyps after puberty. Colon must be resected or 100% progress to colon cancer. Mutation is at chromosome 5q (APC gene) (5 letters in “polyp”). Autosomal dominant.

Question 4

Familial Hypercholesterolemia

Answer 4

Elevated LDL due to due to defective or absent LDL receptor. Severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas (classically the achilles tendon). Autosomal dominant.

Question 5

Hereditary Hemorrhagic Telangiectasia

Answer 5

telangiectasias, recurrent epistaxis, skin discoloration, AVMs, Gi bleeding, hematuria. AKA Osler-Weber- Rendu syndrome. Autosomal dominant.

Question 6

Huntington Disease

Answer 6

depression, progressive dementia, choreiform movements, caudate atrophy. Trinucleotide repeat disorder of gene on chromosome 4 (CAG repeats). Autosomal dominant with anticipation. increase number of repeats, decrease age of onset.

Question 7

Li-Fraumeni syndrome

Answer 7

abnormalities in TP53. multiple malignancies at an early age. Also known as SBLA cancer syndrome (sarcoma, breast, leukemia, adrenal gland). Autosomal dominant.

Question 8

Marfan syndrome

Answer 8

FBN1 mutation on chromsome 15 leading to defective fibrillin (the scaffold for elastin. Tall with long extremities, pectus excavatum, hypermobile joints, tapering of fingers and toes (arachnodactyly); cystic medial necorsis of the aorta. Aortic incompetence leads to dissection. Autosomal dominant.

Question 9

MEN

Answer 9

MEN 1 associated with MEN1 gene. MEN 2A and 2B associated with RET gene. Autosomal dominant.

Question 10

MEN1

Answer 10

hyperparathyroidism
pituitary adenoma
pancreatic tumors (especially

Question 11

MEN 2A

Answer 11

hyperparathyroidism
pheochromocytoma
medullary thyroid cancer

Question 12

MEN 2B

Answer 12

marfan
medullary thyroid cancer
pheochromocytoma

Question 13

NF1

Answer 13

cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheo, Lsich nodules (pigemented iris hamartomas). 100% penetrance, variable experssion. autosomal dominant . mutation on NF1 gene on chromomsome 17. 17 letters in von Recklinghausen.

Question 14

NF2

Answer 14

bilateral acoustic schwannoma, juvenile cataracts, NF2 gene on chromsome 22. 2 –> 22. autosomal dominant.

Question 15

Tuberous Sclerosis

Answer 15

Neurocutaneous disorder. autosomal dominant.

Question 16

von Hippel-Lindau disease

Answer 16

characterized by the development of numerous tumors. both benign and malignant. associated with deletion of VHL gene (tumor suppressor) on chromosome 3P. 3 words Von hippel lindau –> chromosome 3.

Question 17

some autosomal recessive diseases

Answer 17

albinism, cystic fibrosis, glycogen storage disease, hemochromatosis, kartegener syndrome, PKU, sickle cell anemia, thalassemias, Wilson disease

Question 18

Cystic Fibrosis - genetic defect

Answer 18

CFTR gene defect on chromsome 7. often deletion of Phe508. most common lethal genetic disease in caucasian population.

Question 19

Cystic Fibrosis - pathophysiology

Answer 19

CFTR codes for ATP gated Cl channel. This channel secretes Cl in lungs and GI tract, reabsorbs Cl- in sweat glands. Phe508 deletion leads to misfolded protein, protein retained in RER, leading to decreased Cl (and H2O) secretion. Abnormally thick mucus secreted in the lungs.

Question 20

Cystic fibrosis - complications

Answer 20

recurrent pulmonary infections (staph aureus in infancy and pseudomonas as teenager).

pancreatic insufficiency. malabsorption, A, D, E, K vitamin deficiency (fat soluble).

Infertility in men

nasal polyps and clubbing of nails

Question 21

cystic fibrosis - diagnosis

Answer 21

chloride sweat test (>60 meq)

Question 22

X-linked recessive disorders (w/ mnemonic)

Answer 22

Oblivious Female Will Often Giver Her Boys Her x-Linked Disorders 
Ornithine transcarbamylase deficiency 
Wiskott-Aldrich 
Ocular albinism 
G6PD
Hunter syndrome 
Bruton agammaglobulinemia 
Hemophilia A and B
Lesch Nyhan Syndrome 
Duchenne (and becker muscular dystrophy)

Question 23

Duchenne Muscular dystrophy

• cause
• clinical findings
• lab findings
• diagnosis

Answer 23

frameshift or nonsense mutation leading to truncated dystrophin, inhibited muscle regeneration.

• pseudohypertrophy of the calves
• gower

increase CK and aldolase are seen. Western blot and muscle biopsy confirm the diagnosis.

Question 24

Becker muscular dystrophy

Answer 24

due to non frameshift insertions in dystrophin gene. partially. leads to a partially functional protein. less severe disease course. onset in teenage years or early adulthood instead of early childhood.

Question 25

Trinucleotide repeat expansion diseases

Answer 25

Huntington disease (CAG)
Freidrich ataxia (GAA)
Fragile X (CGG)
Myotonic dystrophy (CTG)

Question 26

Trisomy 18
name of syndrome
clinical features
prognosis

Answer 26

Edwards Syndrome
Severe intellectual disability, rocker bottom feet, micorgnathia, low set ears, clenched hands with overlapping fingers, congenital heart disease.
Death usually within 1 yr of birth

Question 27

Trisomy 13
name of syndrome
clinical features
prognosis

Answer 27

Patau Syndrome
severe intellectual disability, rocker bottom feet, micorcpehaly, cleft lip/palate, holoprosencephaly, polydactyly,
death usually occurs within 1 year of birth

Question 28

Trisomy 21
name of syndrome
clinical features

Answer 28

Down Syndrome
intellectual disability, flat facies, prominent epicanthal folds, single palamar crease, sandal gap toes, duodenal atresia, hirshcprung disease, congenital heart defect (ASD), associated with early onset alzheimers, increased risk of AML and ALL.

95 percent of cases are due meiotic non-disjunction
4 percent of cases are due to unbalanced robertsonian translocation (between 14 and 21).

Question 29

Cri-du-chat

Answer 29

congenital microdeletion of the short arm of chromsome 5.
microcephaly, moderate to severe intellectual disability, high pitched crying, epicanthal folds, cardiac abnormality (VSD).

Question 30

Williams syndrome

Answer 30

congenital microdeletion of the long arm of chromsome 7. distinctive “elfin” facies, intellectual disability, hypercalcemia, extreme friendliness with strangers