X-linked ataxias

Abstract

X-linked ataxias are clinically and genetically heterogeneous. Clinically, ataxia may be the sole, the dominant, or a non-dominant phenotypic feature of X-linked ataxias. Ataxia is most commonly of the cerebellar type. Other manifestations in addition to ataxia may be neurological or non-neurological. Ataxia as the exclusive phenotypic feature has been described in X-linked ataxia due to PAMC3 mutations, X-linked adrenoleukodystrophy, and X-linked pyruvate-dehydrogenase defi ciency. X-linked ataxias, in which ataxia dominates include fragile X-tremor ataxia syndrome, X-linked sideroplastic anemia with ataxia, and X-linked ataxia due to GJB1 mutations. Additionally, a number of X-linked disorders with ataxia as a non-dominant feature have been described. The number of X-linked ataxias is steadily increasing and it is quite likely that their number will further increase. Therapy of X-linked ataxias is symptomatic. Genetic counselling not only depends on the X-linked trait of inheritance but also on the presence or absence of germline mosaicism or if the mutation concerns a trinucleotide expansion. Early recognition of X-linked ataxias is warranted to prevent long-term misdiagnosis and application of ineffective treatment.