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114 Cards in this Set
- Front
- Back
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NFI Diagnostic Criteria mnemonic ROLANDO Need 2 or more of: |
R - 1st degree relative with NFI O - Osseous lesion L - > = 2 Lisch nodules A - Axillary freckling N - > = 2 neurofibroma or 1 PLEX NF D - Dime shaped cafe-au-lait (>=6, > 5 mm pre + > 15 mm post pub) O - Optic N glioma |
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Incidence of NF-1 |
1:3000 |
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NF-1 gene and chromosome |
Neurofibromin (NF1 gene) Chr 17 Autosomal dominant |
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Neurologic manifestations of NF-1 |
Optic N glioma Neurofibromas/Schwannomas (Ependymomas, astrocytomas, meningiomas less common than NF2) Learning disabilties, macrocephaly, Epilepsy, Migraine, Aneurysms |
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NF1 patient with stroke What do you suspect? |
Association of Moya Moya disease with NF1 |
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Cafe-au-lait spots |
> = 6 lesions > 5 mm prepubertal > 15 mm postpubertal |
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Name 4 cutaneous manifestations of NF-1 |
- Cafe-au-lait spots - skin freckling 1-3 mm (axilla) aka Crowe's sign -Neurofibromas - Plexiform neurofibromas |
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Systemic manifestations of NF-1 |
- Lisch nodules on Iris - Dysplasia of renal arteries → HTN - Cerebral artery dysplasia causing MOYA MOYA syndrome, aneurysms - Bone dysplasia (Short stature, scoliosis, sphenoid wing dysplasia, pseudoarthrosis)
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Mnemonic For NF2 |
MISME - Multiple, inherited schwannomas, meningiomas, ependymomas |
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MR brain findings in NF 1 |
↑ T2 signal changes in basal ganglia, thalamus, brainstem, cerebellum (UBO- unidentified bright objects) |
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Risk of malignant peripheral nerve sheath tumor in plexiform neurofibroma |
5-10% |
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Management of NF-1 patients Outline |
-Genetic counseling - Annual physical ( BP, growth, stature) - Ophtho exams - Evaluate for learning disability - Scoliosis/ skeletal abn Rx - Surgical Rx of neurofibromas and other tumors |
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Management of NF2 Outline |
Genetic Counseling Yearly MRI brain Hearing evaluation Ophtho exam Spinal MRI to R/O ependymomas? |
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Merlin highly expressed in which tissues? |
Schwann cells Meningeal cells lens nerve cells |
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Lens finding in NF 2 |
Posterior subscapsular cataracts |
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Common tumors associated - NF2 |
Bilat. vestibular Schwannomas Meningioma Ependymoma |
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NF2 gene, chromosome |
Schwannomin or merlin Chromosome 22 Autosomal dominant |
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Systemic features of TS |
Retinal hamartomas Cardiac rhabdomyoma Renal Angiomyolipomas Pulmonary lymphangioleiomyomatosis |
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Neurological features of TS |
Epilepsy Seizures - infantile spasms Mental retardation Behaviour abnormalities Subependymal Nodules Tuber,s SEGA Heterotopic Gray matter |
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Common location for SEGA |
Foramen of Munro - Causes obstructive hydrocephalus |
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Common location for subependymal nodules in TS |
Near caudate nucleus posterior to foramen of Munro along the ventricular surface |
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Which patients tend to have severe disease TSC1 or TSC2? |
TSC2 |
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Vogt's triad in tuberous sclerosis |
Seizures MR Adenoma Sebaceum |
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Function of tuberin/hamartin complex |
Upstream modulator in the mTOR signaling pathway (mammalian target of rapamycin) *Rapamycin inbihits MTOR
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Tuberous Sclerosis Genes |
TSC 1 - Hamartin Chr 9 TSC 2 - Tuberin Chr 16 (TSC 2 more severe phenotype) |
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Malignancy associated with turberous sclerosis |
Renal Cell Carcinoma |
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Cutaneous features of TS |
Ash leaf spots 90% Adenoma sebaceum 75% Ungual fibromas 21% Shagreen patches 19% Confetti lesions Poliosis (white patch/forelock) |
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Incidence of TS |
1:6000 to 9000 |
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Rate of spontaneous mutation in TS |
66-86% |
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Ophthomologic finding in TS |
Retinal hamartomas - mulberry lesions adjacent to disc - plaque like hamartomas - depigmented retinal lesions |
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Renal cysts common in TS Why? |
TSC 2 (hamartin) gene is contaguous with APKD type 1 gene on Chr 16 - hence multiple renal cysts in TS |
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Minor features of TS List 5 |
Dental enamel pits Hamartomatous rectal polyps Bone cysts White matter migration lines Gingival fibromas Non-renal hamartomas Confetti skin lesions Multiple renal cysts |
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Major features of TS List 5 |
Includes cutaneous/systemic/neuro Ash leaf spots Shagreen patch Ungnal fibromas Adenoma sebaceam Retinal hamartoma Cardiac rhabdomyoma Renal Angiomyolipoma Pulomary LAM Cortical tuber SEGA Subependymal nodule (11 major) |
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Drug used in the treatment of SEGA in TS |
Rapamycin (Sirolimus) |
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MRI findings in TS Name 5 |
Subependymal nodules Cortical tubers SEGA Heterotopic gray matter focal cortical hypoplasia |
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Management of Tuberous Sclerosis patients - List |
1. Genetic counseling 2. Seizures - AEDs Infantile spasms - vigabatrin or ACTH surgery for SEGA/tubers 3. Development should be followed 4. US abdo or CT q 1-3 years 5. CXR 6. Dermal abrasion for adenoma sebaceum 7. Rx of renal/pulomary symptoms
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Diagnostic criteria for HHT |
Spontaneous recurrent epistaxis Visceral telengiectasis Affected 1° relative |
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CNS features of HHT |
- Paradoxical embolism via pulm AVF leading to strokes/TIAS - Cerebral abscess or meningitis septic emboli via pulm AVF - Vascular anomalies - Aneurysms Consider HHt in pts with multiple VMS |
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Systemic features in HHT |
Eye/Retinal telengiectasias Pulomary AVMS GU-hematoma GI - hematemesis, melena ENT - epistaxis |
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Osler-Weber-Rendu (HHT) mode of inheritance Genes involved |
AD HHT 1 - endoglin HHT 2 - ALk1 *(activin receptor like kinase) Both endoglin + ALk1 encode proteins on endothelum
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Common presentation of HHT |
Epistaxis in 90% |
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HHT Cutaneous features |
Telangiectasias (mucocutaneous) hands, face, lips, oral cavity, nasal cavity |
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Menkes disease (kinky hair disease) Mode of inheritance Gene |
X-linked recessive ATP7A 9 (aka MNK) gene xq13 |
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ATP7A gene function on Xq13 |
encodes for copper transporting membrane A7Pase which is expressed in all tissues except liver - leads to defective incorporation of CU into enzymes - Copper dependent enzymes affected |
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Menke's disease - Pathogenesis |
1. Copper deficiency 2. Impaired cellular export of Cu leading to accumulation in all tissues except brain and liver. |
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Skull XR finding in Menke's disease |
Wormian bones - Extra sutural bones |
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Cutaneous, features of Menke's disease |
Colorless, kinky hair Loose skin hyperextensible joints (hair = pili torti) (Cu deficiency impairs elastin and collagen cross linking) |
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Blood vessel appearance in Menke's disease |
Tortuous, kinked or dilated due to deficient elastin fibers in blood vessel walls |
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Diagnosis of Menke's disease |
1. low serum copper 2. low ceruloplasmin 3. plasma catecholamine analysis to evaluate for dopamine B hydroxylase deficiency |
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Why is sympathetic adrenergic dysfunction seen in Menke's disease? |
due to impairment of dopamine B hydroxylase that required copper for synthesis of NE and other N7's leading to hypotension, hypothermia, anorexia, somnolence |
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MRI findings in Menke's disease |
Diffuse cortical atrophy Impaired myelination Subdural effusions/hematoma Dilated tortuous vessels |
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Systemic manifestations of Menke's disease |
- Bladder diverticuli - Wormian skull bones (extra sutural bones) - sympathetic adrenergic dysfunction due to impairment of dopamine B hydroxylase |
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CNS manifestations of Menke's disease |
Hypotonia then spastic quadriparesis developmental delay seizures strokes subdurals 2° atrophy |
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Menke's disease - Rx |
Copper replacement Copper - histidine supplementation |
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CTX - CNS findings |
Cognitive impairment Ataxia, neuropathy, Parkinsonism, accelerated atherosclerosis, psychosis |
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Cerebrotendinous Xanthoma CTX |
Autosomal recessive Defect in enzyme 27-sterol hydroxylase (CYP 27) - leads to deposits of cholesterol/cholestanol |
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CTX - lab diagnosis |
plasma and bile levels of cholestanol ↑↑ |
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CTX skin manifestation ocular manifestation |
Achilles tendon xanthomas Cataracts |
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Hypomelanosis of ito - skin manifestations |
1. hypopigmented whorls follows Blaschko's lines 2. cafe-au-lait spots nevus of ota, aplasia cutis, trichorrhexis, focal hypertrichosis mongolian blue spot |
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Hypomelanosis of ITO - CNS manfestations |
Seizures MR Hemimegalencephaly Lissencephaly |
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Hypomelanosis of ITO (incontenentia pigmenti achromians) -Mode of inheritance |
3rd most common NC disorder Autosomal mosaicism X-chr often involved ONLY NC disorder with mosaicism * |
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Blaschko's lines |
Invisible skin lines under N conditions - become visible when some diseases of the skin manifest themselves to these patterns V-shape over the back S-shaped whorls over the chest Wavy shape on the head |
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Systemic manifestations of Hypomelanosis of ITO |
Ocular - microphthalmia, cataracts MSk - scoliosis, short stature Dental - hypoplastic teeth Cleft lip/palate Cardiac -TOF |
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Incontinenta pigmenti Name of the gene, cutaneous feature, neurologic findings |
x-linked dominant NEMO/Idd gene 'marble cake' hyperpigmentation MR and seizures abnormal dentition |
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Stages of incontinentia Pigmenti |
1. Bullous stage 2. Verrucous stage 3. Hyperpigmentation stage 4. Atretic stage |
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Incontinentia pigmenti Inheritance gene |
x-linked dominant Gene NEMO (IkBkG) |
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Pseudoxanthoma elasticum Mode of inheritance Gene involved |
Autosomal recessive ABC C6 gene |
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Systemic manifestations in Pseudoxanthoma elasticum |
Angiod streaks of retina Retinal hemorrhage CV and PVD |
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CNS manifestation of pseudoxanthoma elasticum |
Arterial disease from elastin degeneration cerebral aneurysms |
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Cutaneous finding in pseudoxanthoma elasticum |
Yellowish plaques on skin in the neck, axilla, abdoment inguinal, decubital, popliteal regions - "Plucked chicken" appearance |
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5 genetic disorders associated with stroke |
Fabry's disease HHT, sickle cell NF1, neurocutaneous melanosis MELAS, homocystinuria CADASIL Ehlers - Danlos type 4 Pseudoxanthoma elasticum |
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Parry-Romberg syndrome (progressive facial hemiatrophy) |
-Sporadic occurence - 2° to cortical dysgenesis, dysfunction of sympathetic nervous system - unilateral atrophy of skin/subcut bone - CNS symptoms→epilepsy, mild hempharesis, cog. impairment |
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4 Neurocutaneous syndromes that can cause aneurysms |
Ehler's-Danlos Marfan's Pseudoxanthoma Elasticum Neurofibromatosis HHT |
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5 Neurocutaneous disorders associated with aneurysms |
NF-1 Ehlers-Danlos HHT Fabry's disease Marfan's syndrome Pseudoxanthoma elasticum |
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2 syndromes where heterochromia of Iris seen |
1. Sturge Weber 2. Congenital Horners syndrome |
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Renal cell carcinoma seen in 2 NC disorders |
1. VHL ~ 70% 2. Tuberous sclerosis |
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Epidermal nevus syndrome MR finding |
Megalencephaly ipsilateral to the nevus, cerebral dysplasia, focal pachygyria |
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Xeroderma Pigmentation |
Severe photosensitivity - bullae/ frecking/erythema after sun exposure skin malignancies ocular findings dementia, peripheral neuropathy ataxia, hearing loss |
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Wyborn-Mason Syndrome |
- Facial angiomas in the Vth CN distribution - Retinal vascular malformation - Seizures, HA, SAH, Dandy-Walker |
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Neurocutaneous melanosis -Pathogenesis -What kind of malignancies are seen? |
1. Congenital disorder of melanotic cell development + migration 2. Malignant melanoma transform other malignant tumors include thabdomyosarcoma, maligant schwannoma, liposarcoma |
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Skin finding in neurocutaneous melanosis |
Giant congenital melanocytic nevi > 20 cm |
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CNS structure commonly affected in neurocutaneous melanosis |
Leptomeninges |
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CNS manifestations of neurocutaneous melanosis |
Leptomeningeal melanosis -occurs at base of the base - hydrocephalus - myelopathy 2° to LM invol intracranial melanoma ICH/SAH, MR, seizures |
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Diagnostic criteria for neurocutaneous melanosis |
1. Large/multiple (greater than or equal to 3) congenital nevi in association with meningeal melanosis or melanoma 2. Absence of cutaneous melanoma 3. Absence of meningeal melanoma |
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MR findings in neurocut. melanosis |
T1 shortening due to malanin in LM, cerebellum, thalamus frontal lobes, base of the brain |
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Ehlers-Danlos syndrome Type IV - gene involved |
COL 3A1 encoding ~-1 chain of type 3 collagen on chromosome 2 |
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3 Neurologic manifestation of Ehlers-Danlos |
Arterial dissection C-C fistula Aneurysms |
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2 Cutaneous features seen in Ehlers-Danlos |
Skin hypermobility easy bruising hyperextensible joints |
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Von-Hippel-Lindau Mode of inheritance gene |
Autosomal dominant VHL gene on Chr 3 VHL = 3 words hence chr 3 |
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Systemic manifestation of VHL |
Pancreatic cysts Renal cysts (RCC develops in 70%) Pheochromocytoma Endolymph tumors Islet cell tumors |
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Hallmark of VHL |
Hemangioblastomas - cerebellum - retina - spinal cord |
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Screening protocol for VHL |
- Annual physical /urine test - Ophthalmoscopy - MR brain q 3 y till 50 then q 5 years - Renal U/S - 24 h urine VMA |
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FABRY'S DISEASE mode of inheritance Enzyme Deficiency |
X-linked recessive X q 22 ~ galactosidase A deficiency lysosomal storage disorder |
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Function of ~ galactosidase A |
-GAL breaks down glycophospholipids - Deficiency leads to lysosomal accumulation of ceramide trihexoside and GL3 - Enzyme can be analyzed in cultured leucocytes/fibroblasts |
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CNS manifestations of FABRY's |
Cerebral thrombosis 2° to GL3 deposits or hemorrhage Headaches Dementia |
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Lab diagnosis of FABRY's |
GAL analysis in cultured leucocytes/fibroblasts |
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MRI brain finding in FABRY |
Hyperintense T1 signal to globus pallidus/pulvinar hypointense T2 signal to these regions |
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Type of neuropathy in FABRY |
Small fiber painful neuropathy |
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Renal manifestations of FABRY's |
Renal failure Proteinuria HTN |
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Ocular findings in FABRY's |
- Whorl keratopathy aka cornea verticillata - Tortuous retinal vessels |
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FABRY'S disease skin manifestations |
Angiokeratomas -hyperkeratotic dilated blood vessels - purple black -'Swim trunk' region |
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FABRY's disease mgmt |
- genetic counseling - annual renal/ cariac evaluation - avoid triggers for pain crisis - replacement of ~ - galactosidase A - PLEX reduces ceramide trihexoside - Renal transplantation - CBZ/phenytoin for pain crisis |
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Pain crisis seen in FABRY's |
Acute neuropathic pain Triggers = stress, heat, fatigue, fever, ETOH Acroparesthesias - burning or tingling pain to extremities |
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Sturge-Weber Syndrome (encephalotrigeminal angiometosis) Mnemonic Triple H- GRASS |
Triple H (Hemiatrophy, hemiparesis, hemianopia) G - Glaucoma R - Retardation A - Angioma S - Seizures S - Stain (port wine) |
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Port wine stain - Common location |
V1 division of 5th CN (forehead and upper eyelid) |
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% of port wine stains that are Sturge Weber |
10-20% |
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Sturge-Weber syndrome Ocular findings |
Glaucoma Buphthalmos Amblyopia choroid angiomas Heterochromia of Iris (ipsi hyperpigmentation) |
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Treatment of seizures in SWS |
Medical - AEDS Surgery - hemispherectomy |
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Skull XR finding in SWS |
Tram track calcification 2° to LM calcification |
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MRI brain findings in Sturge Weber |
- leptomeningeal angiomatosis - atrophy of ipsi hemisphere - enlargement of ventricle 2° to atrophy - Gd- enhancement shows the LM angiomatosis |
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Neurologic manifestations of Sturge-Weber |
Seizures (focal motor, atonic, tonic, myoclonic, inf.spasm) focal deficits (triple-H) Developmental delay, learning disorders, MR |
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Pathogenesis of hemianopia in Sturge-Weber |
Parieto-occipital LM angiomas cause hemianopia ? occipital cortex damage |
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Pathogenesis of hemiplegia in Sturge-Weber syndrome |
cerebral ischemia 2° to vascular steal, repeated thrombosis due to leptomening angiomatosis |
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Common location for leptomeningeal angiomatosis in Sturge-Weber |
Parieto-occipital region |
