FABRY DISEASE 12/30/2012. Ataxia-Telangiectasia. Ophthalmologic Signs of Genetic Neurological Disease

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1 Ophthalmologic Signs of Genetic Neurological Disease ES ROACH,MD. Ophthalmologic Signs of Genetic Neurological Disease Conjunctival lesions Corneal lesions Lesions of iris & lens Retinal vascular lesions Cherry red spot Other retinal lesions Ataxia-Telangiectasia Autosomal recessive Progressive ataxia Some PN dysfunction Immune compromise - Absent IgA - Low IgG2 Lymphoid malignancy 12 kb gene at Xq22 Alpha galactosidase A Mildly affected females Angiokeratomata Corneal swirls Painful neuropathy Cardiac failure Renal failure Stroke FABRY DISEASE 1

2 CORNEAL SWIRLS OF FABRY DISEASE FABRY DISEASE IV recombinant alpha galactosidase A (1 mg/kg q 2 weeks). Induced antibodies clear over time. Dose-dependant reduction of glycosphingolipid globotriaosylceramide. 20/29 patients no microvascular endothelial deposits after 20 weeks Less pain, better renal function (GFR, creatinine) Striking improvement in cardiac function Am J Hum Genet 2004; 75:65-74 Other Corneal Opacities NF1: Eye Findings Hurler s (MPS I) Cockayne syndrome Mucolipidosis IV Amyloidosis V Lisch nodules Retinal hamartomas Optic glioma Maroteaux-Lamy (MPS VI) 2

3 NF1: Skin Findings NEUROFIBROMATOSIS NF TYPE 1 Dominant gene 1: 3000 births All have cutaneous Lisch nodules Rare schwannomas CNS: optic gliomas Chromosome 17q11 Neurofibromin NF TYPE 2 Dominant gene 1: births Skin not prominent No Lisch nodules All have schwannomas CNS: menengiomas (60%) Chromosome 22q11 Merlin Café au lait macules Neurofibromas Axillary freckling HOMOCYSTINURIA: CLINICAL FEATURES HOMOCYSTINURIA: CLINICAL FEATURES Neurological Mental retardation Epilepsy Psychiatric symptoms Headaches Ophthalmologic Lens dislocation Myopia Vascular Myocardial infarction Stroke Pulmonary embolism Orthopedic Scoliosis Arachnodactyly Marfanoid Osteoporosis Pectus excavatum Pes cavus Cutaneous Pale, blond Thin hair & skin Livedo reticularis Malar flush 3

4 HOMOCYSTINURIA: INHERITANCE CHERRY RED SPOT Cystathionine ß-synthase (CBS) - most common of several enzyme defects All are autosomal recessive Frequency homozygous CBS 1: K Frequency heterozygous CBS 1:5-7K Central retinal artery occlusion Neuraminidase deficiency CHERRY RED SPOT Disorder Deficient Enzyme Frequency TSC: Skin & Eye Findings Tay-Sachs Hexosaminidase A 90% Sandhoff s disease Hexosaminidase A & B 90% Sialidosis type 1 Neuraminidase 100% Sialidosis type 2 Neuraminidase 80% Niemann-Pick Sphingomyelinase 50% GM1 gangliosidosis Beta-galactosidase 50% Farber disease Ceramidase Rare (Roach ES, et al. Dermatol Clinic 1995; 13: ) 4

5 Von Hippel-Lindau Disease Retinal lesions in about 75% Nodular, achromic, and pigmented lesions Not specific for TSC Vision does not often deteriorate Autosomal dominant Tumor suppressor gene Retinal angiomas Tumor formation - renal carcinoma - Hemangioblastoma (75%) - Pheochromocytoma (7-20%) Fx Bruch membrane Retinal hemorrhages Visual loss - Gradually progressive Etiology - Pseudoxanthoma elasticum - Sickle cell disease - Thalassemia major - Bassen-Kornsweig Angioid Streaks FTT, distention Acanthocytosis Abetalipoproteinemia (Bassen-Kornsweig) Hypotonic & weak Ataxic & areflexic Loss vibration & proprioception Angioid streaks Variable visual loss 5

6 Abetalipoproteinemia (Bassen-Kornsweig) Autosomal dominant (multiple cavernous malformations) Decreased synthesisassembly of lipid transport protein apolipoprotein B, which coats chylomicrons Low vitamin E due to poor absorption RBC: Scanning EM Sjogren-Larsson Syndrome Autosomal recessive Abnormal lipid metabolism Hyperkeratotic areas Crystalline macular deposits Demyelination brain & cord Seizures (33-50%) Progressive dementia Acquired - Trauma - Tumor optic nerve - Increased ICP Genetic OPTIC ATROPHY - Metachromatic - Adrenoleukodystrophy - Leber optic atrophy - Machado-Joseph - Ceroid lipofuscinosis 6

7 Retinitis Pigmentosa Caused by various hereditary retinal defects Degeneration of rod & cone cells Progressive visual loss - Trouble seeing in poor light initially - Diminishing visual field Confirm by ERG test before retinal changes obvious Aicardi Syndrome X-linked dominant Retinal lacunes Absent corpus callosum Intractable epilepsy Mental retardation 7