CAPN1 mutations are associated with a syndrome of combined spasticity and ataxia

Dear Sirs,

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of inherited neurological disorders that are characterized by pyramidal tract affection and variable other neurological manifestations [2]. Mutations in the CAPN1 gene have recently been identified as causative for SPG76 [4]. Homozygous and compound-heterozygous CAPN1 mutations were also found in pedigrees with an overlapping ataxia-spasticity syndrome with or without additional mild cognitive decline and mild axonal peripheral involvement [6]. In addition, a missense CAPN1 mutation was previously associated with spinocerebellar ataxia in the Parson Russell Terrier dog breed [3].

Our 39-year-old female index patient noticed first symptoms of a slowly progressive gait disorder at the age of 29 years (Fig. 1a). Neurological examination revealed mild dysarthria, slightly slowed saccades, spastic tetraparesis predominantly affecting the legs. Muscle tone was severely increased causing action-induced pes equinovarus...