Phenotype of Patients With Charcot-Marie-Tooth With the p.His123Arg Mutation inGDAP1in Northern Finland

Background and ObjectivesMutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene cause autosomal dominant or autosomal recessive forms of Charcot-Marie-Tooth disease (CMT). Our aim was to study the clinical phenotype of patients with CMT caused by heterozygous p.His123Arg inGDAP1.MethodsTwenty-three Finnish patients were recruited from a population-based cohort and through family investigation. Each patient was examined clinically and electrophysiologically. The Neuropathy Symptom Score and the Neuropathy Disability Score (NDS) were used in clinical evaluation.ResultsThe median age at onset of symptoms was 17 years among patients with p.His123Arg inGDAP1. Motor symptoms were markedly more common than sensory symptoms at onset. All patients had distal weakness in lower extremities, and 17 (74%) patients had proximal weakness. Muscle atrophy and pes cavus were also common. Nineteen (82%) patients had sensory symptoms such as numbness or pain. The disease progressed with age, and the NDS increased 8.5 points per decade. Electrodiagnostic testing revealed length-dependent, sensory and motor axonal polyneuropathy. EDx findings were asymmetrical in 14 patients. Genealogic study of the families suggested a founder effect.DiscussionWe found that CMT in patients with p.His123Arg inGDAP1is relatively mild and slow in progression.