Severe familial paroxysmal exercise-induced dyskinesia.

ABSTRACT

Familial paroxysmal exercise-induced dyskinesia (PED) is a rare movement disorder that is mostly caused by mutations in the solute carrier family 2, member 1 (SLC2A1) gene and inherited in an autosomal dominant manner. Clinical, laboratory, and genetic studies were performed in three family members. The proband's symptoms were recorded in a private video. He was placed on clonazepam. The 42-year-old proband presented with a 34-year-history of "dancing fits" suggesting a psychogenic aetiology. They occurred spontaneously or were triggered by physical exercise with a frequency up to six episodes per month, duration up to 30 min and no impairment of consciousness. Cerebrospinal fluid-(CSF)-to-blood glucose ratio was slightly reduced (0.59) and electroencephalograms were unremarkable. His 63-year-old father had less severe symptoms with spontaneous recovery before age of 45. The proband and his 38-year-old only brother also reported daily absence episodes early in the morning with an onset at age three and spontaneous recovery before age 15. Genetic testing revealed a novel c.972G>A, p.S324S heterozygous variant in the SLC2A1 gene in three patients. No splicing defects at the RNA level could be demonstrated. Five milligrams per day of clonazepam allowed for excellent control of PED. PED may produce a broad range of bizarre movements mimicking psychogenic movement disorders. A positive family history suggests an organic aetiology. PED can effectively be treated with clonazepam. Clinical manifestations, autosomal dominant inheritance and CSF findings suggest a causative role of the SLC2A1 gene, although no splicing defect at the RNA level could be demonstrated for the novel variant. Additional studies such as exome sequencing are indicated.