The frequency, and clinical, molecular, and neuropathological features of spinocerebellar ataxia 3 (SCA3) and Machado-Joseph disease (MJD) in 125 autosomal dominant cerebellar ataxia (ADCA) families were analyzed at the Service de Neuropathologie, Hopital de la Salpetriere, Paris, and Service de Neurologie, Hopital de Haut Leveque, Pessac, France; and Service de Neurologie, Hopital des Specialites, Rabat, Morocco. Thirty four families (126 patients) carried the expanded CAG repeat in the MJD1 gene. The length of the CAG repeat influenced the age at onset and the frequency of clinical signs associated with cerebellar ataxia (abnormal DTRs, decreased vibration sense). The frequency of supranuclear ophthalmoplegia, swallowing difficulties, and amyotrophy was significantly correlated with the disease duration. The age at onset varied from 14 to 70 years, mean 36 yrs, for the SCA3/MJD. One patient with SCA2 had an onset of ataxia at 8 years, whereas the youngest with SCA1 was 21. Neuropathological lesions distinguished the varieties of SCA, eg. basal ganglia lesions were more severe in SCA3/MJD than in SCA1. [1]

COMMENT. Despite the infrequent occurrence of Machado-Joseph disease in children, three recent reports from different parts of the world, France, Japan, and Australia, prompted commentary. MJD is an autosomal dominant spinocerebellar degeneration, occurring mainly in people of Portuguese descent. An unstable trinucleotide CAG repeat in MJD maps to the same region of chromosome 14 as the SCA3 locus. Two of 3 patients from Japan noted gait unsteadiness at age 18 years, followed 2 years later by involuntary movements, dysarthria, dysphagia, and hand incoordination [2]. Four families of Australian aboriginal people with MJD exhibited anticipation and an earlier age of onset [3]. MJD should be included in the differential diagnosis of a progressive ataxia with onset in later childhood, adolescence, or adulthood.