POG02 Variant ataxia telangiectasia in siblings with normal α-fetoprotein levels. Issue 11 (22nd October 2010)

• Record Type: Journal Article
• Authors: Albertyn, C; Cawley, N; Taylor, A T M; Srinivasan, V; Last, J I; Murphy, R P
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 81:Issue 11(2010)
• Page Start: e48
• Page End: e48
• Publication Date: 2010-10-22
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp.2010.226340.124
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Introduction: Ataxia telangiectasia (A-T) is a multisystem, degenerative disorder caused by mutation of the A-T mutated ( ATM ) gene. Classic A-T presents with ataxia and ocular telangiectasia in association with immunodeficiency, increased risk for malignancy, increased serum α-fetoprotein levels, radiosensitivity, and chromosomal instability. Variant A-T presents as a milder phenotype with an extended lifespan and may be due to residual ATM kinase activity. Two siblings with variant AT are described. Case Description: The eldest sister is 24-years-old and became wheelchair bound by age 22, following 20 years of progressive gait ataxia. She has choreo-athetoid movements of the arms and neck. Her younger sister is 20-years-old and presents with writing difficulty. She exhibits focal dystonia and blepharospasm, in addition to ocular telangiectasia. She remains independently mobile. Results of Investigations: Both sisters have normal α-fetoprotein levels, with no immunodeficiency or endocrinopathy. Two mutations (c.9022C>T and c.1066-6T>G) were identified. The c.9022 mutation has no ATM kinase activity, but some ATM kinase activity is expressed by the c.1066 mutant allele in cells from these patients. Discussion: These siblings present with a milder phenotype and extrapyramidal signs, in keeping with recent descriptions of variant A-T. The absence of elevated α-fetoprotein levels should not deter physicians in pursuing this diagnosis.