A study by the Institute of Myology has enhanced the phenotypic spectrum due to PLEKHG5 gene mutations

In clinical practice, it is not always easy to distinguish between hereditary motor and sensory neuropathy (the prime example being Charcot-Marie-Tooth disease or CMT) and disorders of the lower motor neuron (referenced under different terms such as distal spinal muscular atrophy, distal motor neuronopathy, etc.). Both clinical and electrophysiological assessment of the sensory component can prove to be delicate or strewn with pitfalls. Furthermore, some genes, such as PLEKHG5, are known to be equally responsible for both phenotypes.

In an article published in June 2021, researchers from the Institute of Myology reported the case of two families, one from Vietnam and the other from the Ivory Coast, in whom intermediate CMT linked to the PLEKGH5 gene was diagnosed further to the discovery of composite heterozygous or homozygous recessive mutations, depending on the case. The novelty of this study resides in the presence of numerous atypical signs. While motor impairment was, in fact, comparable with the data in the literature (distal deficit with fairly limited progression, and little or no sensory impairment), certain aspects were out of the ordinary: all four patients had the distinctive feature of having significantly elevated CPK levels (up to 3,800 units), signal anomalies on brain MRI and, above all, diffuse conduction blocks outside conventional areas of nerve compression.

The authors emphasise the value of considering this form of CMT to avoid prescribing unnecessary, costly treatments.


Leukoencephalopathy and conduction blocks in PLEKHG5-associated intermediate CMT disease. Villar-Quiles RN, Le VT, Leonard-Louis S, Trang NT, Huong NT, Laddada L, Francou B, Maisonobe T, Azzedine H, Stojkovic T. Neuromuscul Disord. 2021 (Juin).S0960-8966(21)00158-9.