Repro 15 - Genetic Disorders: AD And Trinucleotide Repeats

Question 1

What are the features of Autosomal Dominant Polycystic Kidney Disease? What is the cause?

Answer 1

Multiple large cysts not only in kidneys but possible in liver, pancreas, brain and arterial blood vessels. Always bilateral. Presents w/ flank pain, hematuria, hypertension, progressive renal failure. Due to APKD1 on chromosome 16. Associated w/ Berry aneurysms.

Question 2

What is Achondroplasia? What is the cause?

Answer 2

Dwarfism. Due to FGF receptor 3 being turned on. Associated w/ advanced paternal age. Autosomal Dominant, more of a sporadic mutation.

Question 3

What is Familial Adenomatous Polyposis? What is the cause?

Answer 3

Colon covered w/ polyps after puberty. Progresses to colon cancer unless those polyps are removed. Due to mutation of APC gene. Autosomal Dominant.

Question 4

What is Gardner’s syndrome? What is the cause of it?

Answer 4

Autosomal dom. Causes polyps in the colon and tumors outside the colon. Osteomas, lipomas, sebaceous cysts, colon polyps, colon cancer. Caused by mutation of the APC gene.

Question 5

What is Familial Hypercholesterolemia? What is the cause of it?

Answer 5

Type IIA hyperlipidemia. Huge LDL. Caused by defective or absent LDL receptor. Heterozygotes have LDL above 300. Homozygotes have LDLs over 700.

Question 6

What is Hereditary Hemorrhagic Telangiectasia?

Answer 6

Osler-Weber Rend syndrome. Causes Abnormal blood vessel formation: skin, mucous membranes, organs. This causes telangiectasia, recurrent epistaxis, Skin discoloration, Arteriovenous malformation (AVMs), Chronic GI tract bleeding.

Question 7

What is Hereditary Spherocytosis and what is the cause?

Answer 7

Autosomal Dom. Defect in structural framework for RBCs caused by Spectrin defect or ankyrin defect. This causes round-shaped RBCs, increasing blood viscosity, more prone to hemolysis (hemolytic anemia and jaundice). Worsens w/ viral infections. MCHC is elevated: due to membrane loss and red cell dehydration.

Question 8

What is MCHC?

Answer 8

Mean cell hemoglobin concentration, measures the concentration of hemoglobin in a given volume of RBCs.

Question 9

How do we diagnose Hereditary Spherocytosis? How do we treat it?

Answer 9

Dx: Hemolytic anemia, Spherocytes, abnormal osmotic fragility test. Tx: splenectomy.

Question 10

What are the finding of Huntington’s disease in MRI?

Answer 10

Atrophy of caudate nucleus. Enlarged lateral ventricles. Defined sulci. Atrophy of putamen.

Question 11

What is Huntington’s disease?

Answer 11

Autosomal Dom. The 7 C’s of Huntington disease: CAG repeat. Cognitive decline. Caudate atrophy. Chorea. Chromosome “Cuatro”. Cuarenta. acetylCholine decrease. It also causes Depression, decreased level of GABA and acetylcholine in the brain.

Question 12

What is Marfan syndrome and what is the cause of it?

Answer 12

Autosomal Dom, a connective tissue disorder. They are tall, pectus excavatum, long extremities, hyperextendible joints. Due to fibrillin gene mutation. Can also cause cystic medial necrosis of the aorta, causing aortic regurgitation, aortic aneurysm, aortic dissection. Floppy mitral valve that can lead to MVP. Subluxation of the lenses.

Question 13

What gene is associated w/ MEN1?

Answer 13

MEN1 gene.

Question 14

What gene is associated w/ MEN2A and MEN2B?

Answer 14

RET gene.

Question 15

What is MEN?

Answer 15

Autosomal dom. Multiple endocrine Neoplasia. Causes tumors of hormone producing glands.

Question 16

What are the symptoms of MEN1?

Answer 16

The 3 P’s. Pituitary adenomas. Parathyroid adenomas. Pancreatic tumors.

Question 17

What are the symptoms of MEN2A?

Answer 17

[MPP] Medullary thyroid carcinoma. Parathyroid adenomas. Pheochromocytoma.

Question 18

What are the symptoms of MEN2B?

Answer 18

[MMP] Medullary thyroid carcinoma. Mucosal tumors. Pheochromocytoma.

Question 19

What is Neurofibromatosis Type 1 and what is the cause?

Answer 19

AKA von Recklinghausen’s disease. Autosom dom. Caused by mutation of a gene on chrom 17 that is responsible for control of cell division. Cafe-aulet spots, neural tumors, Lysch nodules (pigmented iris hamartomas), scoliosis.

Question 20

What type of Neurofibromatosis is associated w/ bilateral acoustic neuromas?

Answer 20

Neurofibromatosis type 2.

Question 21

What is Neurofibromatosis type 2 and what is the cause?

Answer 21

Hearing loss, tinnitus, balance problems. Cataracts and other neurologic tumors and cutaneous manifestations. Bilateral Caused by mutation on chromosome 22. [On chromosome 2, causes two-ning problems, two sides]

Question 22

What is Tuberous Sclerosis? What is the cause?

Answer 22

Non-malignant tumors in the brain and other organs. Facial lesions (adenoma sebacium). Hypopigmented ashleaf spots on skin. Cortical and retinal hamartomas, causing seizures. Causes intellectual disability. Associated with cardiac rhabdomyomas and astrocytomas. Caused by Mutated hamartin (or tuberin) gene. It has imcomplete penetrance and variable presentation.

Question 23

What is von Hippel-Lindau disease? What is the cause?

Answer 23

An autosomal dom. Causes multiple types of tumors: Hemangioblastomas in retina, cerebellum, medulla. Half of patients develop multiple bilateral renal cell carcinomas. Pheochromocytomas. Associated w/ deletion of the VHL gene, resulting in constant expression of HIF, a transcription factor, which causes activation of angiogenic growth factors, causing the hemangioblastomas.

Question 24

What are the 4 important trinucleotide repeat diseases?

Answer 24

[Hunting for My Fried X] Huntington (CAG). Myotonic dystrophy (CTG). Friedreich ataxia (GAA). Fragile X syndrome (CGG).

Question 25

What does genetic anticipation mean?

Answer 25

Disease severity increases and/or age of the disease onset decreases.

Question 26

What gene defect is responsible for achondroplasia?

Answer 26

FGF receptor.

Question 27

A genetic defect in which protein results in hereditary spherocytosis?

Answer 27

Spectrin or Ankyrin.

Question 28

What autosomal dominant disease is associated w/ floppy mitral valve, dissecting aortic aneurysm, berry aneurysm?

Answer 28

Marfan syndrome.

Question 29

What autosomal dominant disease is associated w/ mitral valve prolapse, liver disease, berry aneurysm?

Answer 29

Autosomal dominant polycystic kidney disease.

Question 30

What autosomal dominant disease causes neural tumors and pigmented iris hamartomas?

Answer 30

Neurofibromatosis type 1.

Question 31

What autosomal dominant disease has a very strong association w/ colon cancer?

Answer 31

Familial adenomatous polyps (FAP).

Question 32

What autosomal dominant disease causes MI before age 20?

Answer 32

Familial hypercholesterolemia.

Question 33

What autosomal dominant disease causes hemangioblastomas of retina/cerebellum/medulla?

Answer 33

Von Hippel-Lindau.

Question 34

What autosomal dominant disease causes increased MCHC, hemolytic anemia.

Answer 34

Hereditary spherocytosis.

Question 35

What autosomal dominant disease causes bilateral acoustic neuromas?

Answer 35

Neurofibromatosis type 2.

Question 36

What autosomal dominant disease causes facial lesions, seizure disorder, cancer risk?

Answer 36

Tuberous sclerosis.

Question 37

What autosomal dominant disease causes caudate atrophy, dementia?

Answer 37

Huntington’s disease.

Question 38

What autosomal dominant disease causes cystic medial necrosis of aorta?

Answer 38

Marfan syndrome.

Question 39

What autosomal dominant disease is caused by defect of fibroblast growth factor (FGF) receptor 3?

Answer 39

Achondroplasia.