A novel mutation inRNF216gene in an Indian case with Gordon Holmes syndrome

Abstract

Early-onset cerebellar ataxia has a broad range of challenging differential diagnoses. Identification of hypogonadism can assist in narrowing down differential diagnosis in the presentation of progressive ataxia. Gordon Holmes syndrome as described by Sir Gordon Holmes in 1908 consists of ataxia with hypogonadism. It is due to mutation inRNF216andOTUD4genes which encode for enzymes in the ubiquitin-proteasome system. In this case report, we describe a 30-year-old male presenting with insidious-onset progressive ataxia with hypogonadotropic hypogonadism, cataract, pan-cerebellar atrophy with bilateral cerebral white matter hyperintensities and a positive homozygous mutation forRNF216making the diagnosis of Gordon Holmes syndrome. The presence of hypogonadism in a patient with ataxia should alert the clinician to look for such a diagnosis.