Overview
Recognise Friedreich ataxia and other inherited ataxia patterns, choose genomic tests that detect repeat expansions, and coordinate syndrome-specific cardiac, endocrine, neurological and family care.
Hereditary ataxias are genetically diverse and can be autosomal dominant, autosomal recessive, X-linked or mitochondrial. The same gene may produce a variable phenotype, and the same clinical syndrome can arise from many genes. A three-generation pedigree should record age at onset, gait, neuropathy, eye movement, hearing, cognition, epilepsy, autonomic symptoms, cardiomyopathy and unexplained early deaths. Apparent absence of family history does not exclude recessive inheritance, de novo change, adoption, non-paternity, limited family size or late-onset dominant disease.
Friedreich ataxia is the archetypal recessive multisystem ataxia. Degeneration of dorsal-root ganglia and posterior columns causes sensory loss; spinocerebellar and corticospinal tracts add incoordination and pyramidal signs; peripheral neuropathy reduces reflexes. Cardiomyopathy and diabetes need active surveillance even when gait dominates the consultation. Most affected people have GAA expansions on both alleles, while a minority have an expansion and another pathogenic FXN variant, so laboratory strategy and phenotype correlation matter.
Other useful patterns include dominant polyglutamine spinocerebellar ataxias with anticipation, ataxia-telangiectasia with immunodeficiency and malignancy risk, ataxia with vitamin E deficiency, Wilson disease, mitochondrial syndromes, episodic ataxias and RFC1 disease. Some have targeted treatment or surveillance. Genomic diagnosis should therefore follow exclusion of acquired causes and be accompanied by consent covering uncertain results, incidental or familial implications, reproductive options and the limits of a negative test.