Phenotype of Patients With Charcot-Marie-Tooth With the P.His123Arg Mutation in in Northern Finland

Overview

Journal Neurol Genet

Date 2021 Oct 11

PMID 34632054

Citations 3

Authors

Maria Lehtilahti

Mika Kallio

Kari Majamaa

Mikko Karppa

Affiliations

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Abstract

Background And Objectives: Mutations in the ganglioside-induced differentiation-associated protein 1 () 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 in .

Methods: Twenty-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.

Results: The median age at onset of symptoms was 17 years among patients with p.His123Arg in . 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.

Discussion: We found that CMT in patients with p.His123Arg in is relatively mild and slow in progression.

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