Study Examines Charcot-Marie-Tooth Type 4C in Norway, Identifies 6 New Mutations

Ana Pena, PhD avatar

by Ana Pena, PhD |

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PRX gene mutation

Charcot-Marie-Tooth (CMT) disease type 4C is the most common recessive form of the disease in Norway. Researchers, looking at all known Norwegian patients with CMT4C, also found six new mutations that cause the disease.

The study, “Charcot-Marie-Tooth disease type 4C in Norway – Clinical characteristics, mutation spectrum and minimum prevalence” was published in the journal Neuromuscular Disorders.

CMT4C, also known as autosomal recessive demyelinating disease, is a rare and severe type of CMT marked by damage to the myelin sheath, a thin layer that protects the nerves fibers.

The disease is caused by mutations in the SH3TC2 gene, which is expressed in the nervous system and gives instructions for the production of a protein whose function is still unknown.

This type of CMT is inherited in an autosomal recessive manner, which means an individual will develop it only if he or she inherits a mutated copy of SH3TC2 from both parents.

This rare type of CMT is prevalent in certain ethnic groups, including those coming from north Africa. Prior studies also suggested a particularly high prevalence of CMT diseases in Norway.

In the study, researchers aimed to estimate the prevalence and the disease manifestations of the specific CMT4C type in Norway. Researchers analyzed medical data from all the registered cases of CMT4C in Norway, including patient-reported symptoms and hospital medical records.

A total of 35 patients from 31 families were found with CMT4C, which indicates a minimum prevalence of 0.7 persons per 100,000 people in Norway, a “relative high minimum prevalence” according to researchers.

In addition, six new types of SH3TC2 mutations were identified among the patients.

Regarding disease manifestations, sensory nerve impairment was present in all patients, while scoliosis (abnormal curvature of the spine), sensory ataxia (imbalance in the senses’ input into the control of movement), and childhood disease onset (in the first decade of life) affected a majority of them.

Other prominent features were weakness (paresis) in the proximal muscles of the legs and cranial nerve involvement, seen in about half of the patients.

Overall, the study shows that CMT4C is the most common recessive CMT in Norway and added insight about the clinical manifestations of the rare type of disease, for which few studies are available.

“In addition to the classic distal limb affection, early debut, scoliosis, proximal paresis, cranial nerve affection and sensory ataxia are the most prominent features of CMT4C,” the researchers wrote.

“[S]ome of the non-typical CMT symptoms like proximal paresis and cranial nerve involvement may have been overlooked in these patients,” and “Genetic analysis should be performed to confirm the diagnosis,” the researchers concluded.