Abstract

Ataxia telangiectasia (AT) is an autosomal recessive disorder, characterised by cerebellar ataxia, immunodeficiency and susceptibility to malignancy. Classic forms of AT result from complete loss of ATM function, while milder variant forms are associated with residual ATM activity. We report a 40-year-old woman with a 30 year history of mild generalised chorea, but late development of cerebellar signs and dystonia but no typical systemic features. A raised α-fetoprotein prompted further tests: MRI showed cerebellar atrophy, and increased chromosomal sensitivity to ionising radiation with complete absence of ATM activity was demonstrated. Genetic analysis showed compound heterozygosity for two known null mutations in ATM. Although these findings predict a severe clinical form of AT, to our knowledge this patient has the mildest reported clinical phenotype associated with two null ATM mutations. Although there is a previous report of a two null ATM mutations in a sib pair associated with a mild neurological presentation, both these individuals developed other neurological signs in their teens. This case underlines the utility of α-fetoprotein testing in patients with movement disorders, significantly broadens the clinical spectrum of AT and emphasises that ATM activity alone does not reliably predict clinical phenotype. Identifying presumed genetic or epigenetic modifiers may elucidate the pathophysiology of neuronal death/dysfunction in AT which remains poorly defined.