A 22-year-old male of Portuguese Azorean descent, presenting at age 16 years with postural instability and falls and developing severe generalized dystonia by age 20 years, is reported from the Center for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada. His parents were first cousins and each had a parent clinically affected by Machado-Joseph disease (MJD). Examination demonstrated in addition to dystonia, slurred speech, horizontal nystagmus, limitation of upward-gaze, unsustained ankle clonus, and flexor plantar reflexes. MRI revealed slight atrophy of the cerebellar vermis. Linkage studies confirmed the recent mapping of the MJD gene to chromosome 14q, and genotyping of the members of this pedigree indicated that this patient was homozygous for the MJD gene. Gene dosage is an important determinant of age at onset and clinical phenotype in MJD. [1]

COMMENT. Three major phenotypes of MJD are described: Type I, Joseph type, with early age of onset and prominent extrapyramidal signs - dystonia, athetosis, rigidity, as well as pyramidal signs; Type III, Machado type, with later onset, cerebellar signs and peripheral neuropathy; and Type II, intermediate type, both with respect to age of onset and clinical features. Juvenile onset of MJD is very uncommon, occurring in only 5 of 143 Portuguese patients cited by these authors.