SCA 37

Importance  To provide clinical and genetic diagnoses for patients' conditions, it is important to identify and characterize the different subtypes of spinocerebellar ataxia (SCA).

Objective  To clinically and genetically characterize a Spanish kindred with pure SCA presenting with altered vertical eye movements.

Design  Family study of ambulatory patients. Electro-oculographic and genetics studies were performed in 2 referral university centers.

Setting  Primary care institutional center in Spain.

Participants  Thirty-six participants from a large Spanish kindred were clinically examined, and 33 family members were genetically examined. Detailed clinical data were obtained from 9 affected relatives. Two ataxic siblings and 2 asymptomatic family members were examined using an enhanced clinical protocol for a follow-up period of 7 years.

Main Outcomes and Measures  High-density genome-wide single-nucleotide polymorphism arrays, along with microsatellite analysis, and genetic linkage studies were performed. Whole-exome sequencing was used for 2 affected relatives. For most patients, the initial symptoms included falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. For all 9 affected relatives, we observed altered vertical eye movements, as initial ocular signs for 3 of them and for the 2 asymptomatic family members, all having inherited the risk haplotype. Neuroimaging showed isolated cerebellar atrophy.

Results  Initial genome-wide linkage analysis revealed suggestive linkage to chromosome 1p32. Multipoint analysis and haplotype reconstruction further traced this SCA locus to a 0.66-cM interval flanked by D1S200 and D1S2742 (zmax = 6.539; P < .0001). The causative mutation was unidentified by exome sequencing.

Conclusions and Relevance  We report a new subtype of SCA presenting in patients as slow progressing ataxia with altered vertical eye movements linked to a 11-megabase interval on 1p32. The Human Genome Nomenclature Committee has assigned this subtype of ataxia the designation SCA37.

JAMA Neurol. 2013;70(6):764-771. doi:10.1001/jamaneurol.2013.2311.

Nature Reviews Neurology June 2013