Abstract
Background and Objectives Mutations 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 in GDAP1.
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 GDAP1. 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 GDAP1 is relatively mild and slow in progression.
Glossary
- CCV=
- compound conduction velocity;
- CMT=
- Charcot-Marie-Tooth;
- CTS=
- carpal tunnel syndrome;
- GDAP1=
- ganglioside-induced differentiation-associated protein 1;
- mRS=
- modified Rankin Scale;
- NCS=
- nerve conduction study;
- NDS=
- Neuropathy Disability Score;
- SCV=
- sensory conduction velocity
Footnotes
Go to Neurology.org/NG for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
- Received May 12, 2021.
- Revision received July 22, 2021.
- Accepted in final form August 11, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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