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The phenotype of the Gly94fsX222 PMP22 insertion
Sara D J de Vries1, Camiel Verhamme, Fred van Ruissen
1Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Abstract:
Point mutations in PMP22 are relatively rare and the phenotype may vary from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe Charcot-Marie-Tooth type 1 (CMT1). We describe the phenotype of the Gly94fsX222 mutation in the PMP22 gene. Medical records of all patients were reviewed and 11 patients were re-examined. EMG was carried out in nine patients and nerve biopsy in one. Thirteen patients originating from seven families with a Gly94fsX222 mutation were included and consisted of 10 women and 3 men with a median age of 41 years (range 7-67). Five index patients were originally suspected of CMT1. Ten patients had abnormal motor skills during childhood. Nine patients had a history of pressure palsies. Involvement of the olfactory, trigeminal, facial, and pudendal nerves occurred in three patients. Twelve patients had pes cavus and one scoliosis. Distal anterior leg and distal arm weakness were found in 12 and 4 patients, respectively. Twelve patients had distal leg sensory abnormalities. Electrophysiological examination revealed a demyelinating sensorimotor neuropathy, both resembling CMT1 and HNPP. Sural nerve biopsy showed demyelinating neuropathy with presence of tomacula. More than three-fourths of the patients with Gly94fsX222 mutation demonstrated a CMT1 phenotype combined with transient deficits. Clinicians should test for this mutation in those patients exhibiting a generalised neuropathy combined with compressive like episodes.
Insights
The Gly94fsX222 mutation in the PMP22 gene causes a neuropathy that often presents as Charcot-Marie-Tooth type 1 (CMT1) with temporary deficits, alongside hereditary neuropathy with liability to pressure palsies (HNPP)-like symptoms.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Point mutations in the PMP22 gene are uncommon.
- These mutations can lead to a spectrum of neuropathies, from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe Charcot-Marie-Tooth type 1 (CMT1).
Purpose of the Study:
- To describe the clinical and electrophysiological phenotype of the Gly94fsX222 mutation in the PMP22 gene.
- To investigate the presentation of this specific PMP22 mutation in affected individuals.
Main Methods:
- Review of medical records for 13 patients from seven families with the Gly94fsX222 mutation.
- Clinical re-examination of 11 patients, including electrophysiological studies (EMG) in nine and nerve biopsy in one.
Main Results:
- The Gly94fsX222 mutation presented as a demyelinating sensorimotor neuropathy, resembling both CMT1 and HNPP.
- Common features included pes cavus (12 patients), distal leg weakness and sensory abnormalities (12 patients), and a history of pressure palsies (9 patients).
- Over three-fourths of patients showed a CMT1 phenotype with transient deficits, and nerve biopsy revealed demyelination with tomacula.
Conclusions:
- The Gly94fsX222 PMP22 mutation often results in a phenotype combining CMT1 features with transient deficits and HNPP-like episodes.
- Clinicians should consider testing for this mutation in patients with generalized neuropathy and recurrent compressive-like episodes.
