Autosomal dominant cerebellar ataxia with slow ocular saccades, neuropathy and orthostatism: a novel entity?

BACKGROUND We describe the clinical characteristics of a Swedish family with autosomal dominant cerebellar ataxia, sensory and autonomic neuropathy, additional neurological features and unknown genetic cause. METHODS Fourteen affected family members were identified. Their disorder was characterized by neurological examination, MRI, electroneurography, electromyography, MIBG-scintigraphy, and tilt-testing. RESULTS The disorder presented as a balance and gait disturbance starting between 16 and 47 years of age. Cerebellar ataxia progressed slowly over the course of decades, and MRI showed mild to moderate cerebellar atrophy. Sensory axonal polyneuropathy was the most prominent additional feature and occurred in all patients examined. Autonomic neuropathy caused pronounced orthostatic dysregulation in at least four patients. Several affected members showed muscle wasting, and mild upper or lower motor neuron signs were documented. Patients had no nystagmus but slow or hypometric horizontal saccades and ocular motor apraxia. Cognition remained unimpaired, and there were no non-neurological disease manifestations. The disorder affected men and women in successive generations in a pattern compatible with autosomal dominant inheritance without evidence of anticipation. A second family where 7 members had very similar symptoms was identified and its origin traced back to the same village in southern Sweden as that of the first family's ancestors. All relevant known genetic causes of cerebellar ataxia were excluded by a novel next-generation sequencing approach. CONCLUSION We present two probably related Swedish families with a characteristic and novel clinical syndrome of cerebellar ataxia and sensory polyneuropathy. The study serves as a basis for the mapping of the underlying genetic cause.