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.