Amyotrophic lateral sclerosis -plus patient with an intermediate-length CACNA1A allele: a Case Report

Amyotrophic lateral sclerosis (ALS), the most common type of motor neuron disease, primarily manifests as progressive weakness, atrophy, fasciculations, bulbar palsy, and pyramidal tract symptoms. Accumulating evidence indicates that the pathological spectrum of ALS extends beyond the pyramidal and neuromuscular motor systems, involving additional brain regions, manifesting as ALS-plus syndrome. We present a case of an elderly woman with bulbar-onset ALS accompanied by cerebellar manifestations and an intermediate-length CACNA1A allele. Based on the Gold Coast criteria, ALS diagnosis was made. Notably, the patient exhibited cognitive impairment and a positive Romberg sign, suggesting a broader phenotypic spectrum. Genetic analysis showed a CAG repeat genotype of 10/20 in the CACNA1A gene. The patient's son carried a 14/20 genotype and displayed isolated cerebellar ataxia without motor neuron features. We reviewed the literature on spinocerebellar ataxia (SCA) co-occurring with motor neuron disease and discussed the uncertain significance of the intermediate-length CACNA1A allele in this context, weighing coincidental co-occurrence against a potential causal link. To our knowledge, this case is the first reported instance of an intermediate-length CACNA1A allele co-occurring with ALS in Chinese population, although the association between the allele and ALS remains unclear.