Autosomal Dominant Diseases

Question 1

Achondroplasia physical symptoms

Answer 1

Short arms and legs
Large head
Frontal bossing and midface retrusion

Question 2

Other achondroplasia symptoms

Answer 2

Hypotonia
Motor milestones off
Craniocervical junction compression

Question 3

What is normal in achondroplasia

Answer 3

Intelligence and life span

Question 4

Frontal bossing

Answer 4

Protruding foreheard

Question 5

Midface returison

Answer 5

Underdevelopment of mailla in length or depth

Question 6

Hypotonia

Answer 6

Muscles undertoned

Question 7

Craniocervical junction compression

Answer 7

Compression of bony abnormalities of occipital bone, foramen magnum, or first 2 cervical vertebra…decrease space for lower brain stem and cervical cord

Question 8

Genetic basis - achondroplasia

Answer 8

2 mutations in FGFR3 gene….glycine 380 replaced by arginine…causes receptor to be overly active…inhibits chondrocyte proliferation and leads to bone abnormalities

Question 9

Heredirary Hemorrhagic Telangiectasia other name and clinical summary

Answer 9

HHT - Osler-Weber-Rendu syndrome

Disorder of blood vessels

Question 10

Characterization of HHT

Answer 10

AVMs lacking capillaries and having direct artery vein connections
Small AVMs (telangiectases) close t osurface of skin and mucous membranes that bleed after slight trauma
Nosebleeds at 12 years (epistaxis)
Some have GI bleeding
Large AVMs in brain, liver, or lungs can cause other problems

Question 11

Telangiectases

Answer 11

Widened venules (tiny blood vessels) that cause threadlike lines or patterns on skin (spider veins)

Question 12

HHT genetic basis

Answer 12

Mutations in genes in the TGF-B/BMP signaliing cascade…ENG, ACVRL1, SMAD4, GDF2

Question 13

ENG

Answer 13

Codes cell surface coreceptor endoglin

Question 14

ACVRL1

Answer 14

ALK1 (same thing)…encodes surface cell receptor

Question 15

SMAD4

Answer 15

Encodes an intracellular signaling molecule

Question 16

GDF2

Answer 16

Gene encoding a growth/differentiation factor and 2 other unidentified genes

Question 17

TGF-B/BMP signaling cascade

Answer 17

Important in cell growth/development/regulation….Important in angiogenesis (formation of new blood vessels)

Question 18

Tuberous sclerosis suummary

Answer 18

Neurocutaneous disorder affecting multiple organs…CNS tumors and renal disease

Question 19

TSC abnormalities

Answer 19

Skin 
Brain 
Kidney 
HEart 
Lungs

Question 20

Hypomelanotic macules

Answer 20

Hypopigmented lesions (ash-leaf spots)

Question 21

Facial angiofibromas

Answer 21

Benign growths on face

Question 22

Shagreen patches

Answer 22

Area of thickened, peblly skin

Question 23

Cephalic plaques

Answer 23

A fibromatous, soft, skincolored or bown plaque typically on forehead or scalp

Question 24

Ungual fibromas

Answer 24

Fibrous grwoth of finger/toenals

Question 25

Cortical dysplasias

Answer 25

Top layer of brain doesn't form properly

Question 26

Subependymal nodules

Answer 26

Abnormal swollen glial cells and bizzare multinucleated cells

Question 27

SEGAs

Answer 27

Subependymal giant cell astrocytomas | Low grade brain tumor that arises in ventricles of brain

Question 28

Angiomyomas

Answer 28

Benign tumor of striated muscle

Question 29

Lymphangioleiomyomatosis

Answer 29

Abnormal growth of muscle and blood vessels lining lungs airways

Question 30

Genetic basis TSC

Answer 30

TSC1 and TSC 2 gene mutations....TSC1 codes for hamartin...interacts with tuberin (coded by TSC2)...2 protein help control cell hrowht and size and are tumor suppressors....do this by interacting with and regulate other proteins

Question 31

VHL characterization

Answer 31

Hemangioblastomas Renal cysts and clear cell renal cell carcinoma Pheochromocytoma, pancreatic cysts, and neuroendocrine tumors Endolympahtic sac tumors Epididymal and broad ligaments cysts

Question 32

Hemangioblastomas in brain can cause

Answer 32

Headaches, vomiting, ataxia

Question 33

Spinal cord hemangioblastomas can cause

Answer 33

pain and sensory/motor loss

Question 34

Retinal hemangioblastomas cause

Answer 34

Loss of vision

Question 35

Lead cause of mortality VHL

Answer 35

Renal carcinomas

Question 36

Leading cause of tuberous sclerosis morbidity

Answer 36

CNS tumors and then renal disease

Question 37

Hemangioblastomas

Answer 37

Tumors of CNS with organs in vascular system

Question 38

Celar cell renal cell carcinoma

Answer 38

Cortical tumor characterized by malignant epithelial cells with clear cytoplasm

Question 39

Pheochromocytoma

Answer 39

Tumor of adrenal gland....hypertension

Question 40

Endolymphatic sac

Answer 40

Membranous strucutre in inner ear

Question 41

Genetic basis of VHL

Answer 41

VHL gene...codes for pVHL which is part of VCB-CUL2 complex...involved in targeting proteins for degradation...pVHL has tumor suppressor activity and involved in ECM formation