Neurocutanoeus syndromes Flashcards
(35 cards)
Name the 3 types of neurofibromatosis
3 distinct disorders
1) NF-1
2) NF-2
3) schwannomatosis
-increased propensity for tumor development, particularly nerve sheath
-90% of cases are NF-1
Discuss the genetics of neurofibromatosis 1 ( Von Recklings disease)
- Autosomal dominant disorder
-mutations in neurofibromin (NF1) a tumor suppressor gene - NF1 is located on chromosome 17q11.2 encodes GAP related protein neurofibronin
- neurofibronin is a cytoplasmic protein that negatively regulates Ras activation
-Ras like other G proteins is dependant on GTP binding for its full activity and GAP proteins shutt off the signal by accelerating the hydrolysis of GTP to GDP - 50% are sporadic mutations and mosaic/segmental disease
Diagnostic criteria of neurofibromatosis type 1 (von recklinghausen)
Manifestations of NF1 by age of presentation
Name clinical features of Neurofibromatosis 1
Other manifestation:
1) Other tumors - neurofibrosarcoma, rhabdomyosarcoma, pheochromocytoma, Wilms tumor, chronic myelogenous leukemia
2) Hypertension may develop as result of pheochromocytoma or renal vascular stenosis secondary to fibromuscular dysplasia
3) Vascular anomalies of CNS including stenoses, moyamoya, aneurysm
4) nevus anemicus found in up to 50% of patients
5) Malignant transformation of neurofibroma secondary to second mutation, most commonly in p53
6) Strong triple association between NF1, juvenile xanthogranuloma, juvenile chronic myelogenous leukemia
7) Watson syndrome = NF 1 features + pulmonic stenosis
Name key features of neurofibromatosis type 2 (bilateral acoustic schwannomas)
-genetics
-clinical features
-prognosis
Discuss the pathogenesis of tuberous sclerosis
1) AD disorder
2) mutation in hamartin (TSC1) located on chromosome 9q34 or tuberin (TSC2) located on chromosome 16p13 which are tumor suppressor genes
3) TSC1 (hamartin) interact with TSC2 (tuberin) and negatively regulates signalling by the small GTPase Rab and Rheb. Like Ras, the activity of Rab and Rheb is dependent on bound GTP and tuberin (like neurofibronin) accelerates hydrolysis of GTP to GDP in order to turn off Rhab and Rheb
4) Rapamycin (sirolimus) and its analogues form a complex eith FK506-binding protein-12 and together they bind to and inhibit mTOR
5) Abnormal regulation of cellular differentiation, proliferation and migration of affected cell types with hamartomas
Describe the clinical features of tuberous sclerosis complex (TSC)
Cutaneous manifestation of TSC by average age of presentation
8 subtypes of neurofibromatosis (Riccardis classification)
Discuss clinical cutanoeus feautures of neurofibromatosis type 1
Discuss clinical features of the other systems in neurofibromatosis type 1
Discuss the management of neurofibromatosis type 1
Make key notes on histology in neurofibromatosis type 1
Make key notes on
1) diff dx of neurofibromatosis 1
2) Treatment of Nf1
3) Prognosis of NF1
Picture (sketch) of NF1
Make key notes on neurofibromatosis type 2
1) criteria
2) clinical features
3) complications
4) screening/work-up
Sketch of neurofibromatosis 2
Name the cutaneous features of tuberous sclerosis
Extra cutaneous features of tuberous sclerosis
Management of tuberous sclerosis
Sketch of tuberous sclerosis
Major clinical features of neurofibromatosis 1
Key features of neurofibromatosis type 2
