Autosomal Dominant Diseases Flashcards
Achondroplasia physical symptoms
Short arms and legs
Large head
Frontal bossing and midface retrusion
Other achondroplasia symptoms
Hypotonia
Motor milestones off
Craniocervical junction compression
What is normal in achondroplasia
Intelligence and life span
Frontal bossing
Protruding foreheard
Midface returison
Underdevelopment of mailla in length or depth
Hypotonia
Muscles undertoned
Craniocervical junction compression
Compression of bony abnormalities of occipital bone, foramen magnum, or first 2 cervical vertebra…decrease space for lower brain stem and cervical cord
Genetic basis - achondroplasia
2 mutations in FGFR3 gene….glycine 380 replaced by arginine…causes receptor to be overly active…inhibits chondrocyte proliferation and leads to bone abnormalities
Heredirary Hemorrhagic Telangiectasia other name and clinical summary
HHT - Osler-Weber-Rendu syndrome
Disorder of blood vessels
Characterization of HHT
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
Telangiectases
Widened venules (tiny blood vessels) that cause threadlike lines or patterns on skin (spider veins)
HHT genetic basis
Mutations in genes in the TGF-B/BMP signaliing cascade…ENG, ACVRL1, SMAD4, GDF2
ENG
Codes cell surface coreceptor endoglin
ACVRL1
ALK1 (same thing)…encodes surface cell receptor
SMAD4
Encodes an intracellular signaling molecule
GDF2
Gene encoding a growth/differentiation factor and 2 other unidentified genes
TGF-B/BMP signaling cascade
Important in cell growth/development/regulation….Important in angiogenesis (formation of new blood vessels)
Tuberous sclerosis suummary
Neurocutaneous disorder affecting multiple organs…CNS tumors and renal disease
TSC abnormalities
Skin Brain Kidney HEart Lungs
Hypomelanotic macules
Hypopigmented lesions (ash-leaf spots)
Facial angiofibromas
Benign growths on face
Shagreen patches
Area of thickened, peblly skin
Cephalic plaques
A fibromatous, soft, skincolored or bown plaque typically on forehead or scalp
Ungual fibromas
Fibrous grwoth of finger/toenals
Cortical dysplasias
Top layer of brain doesn’t form properly
Subependymal nodules
Abnormal swollen glial cells and bizzare multinucleated cells
SEGAs
Subependymal giant cell astrocytomas
Low grade brain tumor that arises in ventricles of brain
Angiomyomas
Benign tumor of striated muscle
Lymphangioleiomyomatosis
Abnormal growth of muscle and blood vessels lining lungs airways
Genetic basis TSC
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
VHL characterization
Hemangioblastomas
Renal cysts and clear cell renal cell carcinoma
Pheochromocytoma, pancreatic cysts, and neuroendocrine tumors
Endolympahtic sac tumors
Epididymal and broad ligaments cysts
Hemangioblastomas in brain can cause
Headaches, vomiting, ataxia
Spinal cord hemangioblastomas can cause
pain and sensory/motor loss
Retinal hemangioblastomas cause
Loss of vision
Lead cause of mortality VHL
Renal carcinomas
Leading cause of tuberous sclerosis morbidity
CNS tumors and then renal disease
Hemangioblastomas
Tumors of CNS with organs in vascular system
Celar cell renal cell carcinoma
Cortical tumor characterized by malignant epithelial cells with clear cytoplasm
Pheochromocytoma
Tumor of adrenal gland….hypertension
Endolymphatic sac
Membranous strucutre in inner ear
Genetic basis of VHL
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
