A novel neurodegenerative disease characterised by posterior column ataxia and pyramidal tract involvement maps to chromosome 8p12-8q12.1.

T he recent barrage of linkage assignments and gene discoveries has confirmed the clinical and genetic heterogeneity of ataxic diseases. They all share the prototypic feature of difficulty in walking though many additionally present dysarthria, spasticity, retinopathy, and other neurological symptoms. Broad subgroups of ataxias and related diseases exist including spinocerebellar and spastic ataxias, each with their own characteristic features. The clinical and genetic heterogeneity of ataxias is best represented by the autosomal dominant cerebellar ataxias (ADCAs). Indeed, a minimum of 22 loci have been discovered, including those for the spinocerebellar ataxias (SCA1–8, SCA10–17, SCA19, SCA21, and SCA22), the episodic ataxias EA1 and EA2, and the complex disorder, dentatorubropallidoluysian atrophy (DRPLA). Similarly, Friedreich’s ataxia (FRDA) is an autosomal recessive disease which affects the spinocerebellar and pyramidal tracts. Symptoms are typically noticed before 20 years of age and include dysarthria, nystagmus, areflexia, and a positive Babinski sign. Hereditary spastic ataxia (HSA) is characterised by retinopathy, muscle wasting, nystagmus, and dysarthria. Spastic ataxia (SAX1) is the first described dominant form, while the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is one of a number of recessive forms. All told, the loci responsible for a significant proportion of hereditary causes of ataxias still have not been elucidated. A large amount of heterogeneity is also observed within the hereditary neuropathies. These include the hereditary sensory neuropathies (HSNs) and the more common hereditary motor and sensory neuropathies (HMSNs). Sensory ataxia is not present in the HSNs, since they affect mainly the unmyelinated and small myelinated nerve fibres, nor is it present in the HMSNs, where sensory symptoms are seldom the presenting complaint. A few rare families have been described with a hereditary sensory-motor neuropathy associated with ataxia (SMNA) of neuropathic origin. These can include both central and peripheral nervous system involvement and neurogenic muscle atrophy. Similarly, a combination of ataxia originating in the cerebellum with signs of peripheral neuropathy has been reported. Neuropathies that affect large myelinated peripheral nerve fibres or their cell bodies located in the dorsal root ganglia can induce a sensory ataxia. Both preganglionic and postganglionic sensory nerve fibres are implicated in these forms of sensory ataxias. Here we report an eastern Canadian family from New Brunswick with Anglo-Saxon ancestry. The family has a novel neurodegenerative disease characterised by sensory (posterior column) ataxia and variable pyramidal weakness but with no overt signs of peripheral sensory or motor neuropathy. This suggests a pure sensory ataxia caused primarily by involvement of the preganglionic sensory nerve fibres (posterior column). To describe this distinct diagnostic entity, we propose the term autosomal dominant sensory ataxia (ADSA).