Dados do Trabalho

Título

Genotypic and phenotypic spectrum of FIG4 variants in Charcot Marie Tooth disease

Resumo

Charcot Marie Tooth disease (CMT) type 4J is a rare inherited peripheral neuropathy, affecting less the 1% of patients with CMT. It is caused by biallelic disease causing variants in FIG4 gene, with patients presenting a variable phenotype and onset ranging from early childhood to adulthood. According to the literature, most individuals typically have both proximal and distal asymmetric muscle weakness of the upper and lower limbs. In addition to the CMT phenotype, pathogenic variants in FIG4 gene have also been related to motor neuron disase, bilateral temporooccipital polymicrogyria, and Yunis‐Varon syndrome. Here, we describe the clinical, genetic, neurophysiological and other ancillary data from 3 unrelated individuals with CMT4J evaluated at two referral centers for neuromuscular diseases. All patients have early-onset disease, with symptoms beginning before age 5 years, and ENMG exam with a demyelinating pattern. One of the patients started to use a wheelchair as a mobility aid at the age of 43 and the other 2 patients maintain an independent gait. Two patients who underwent brain MRI did not have significant radiological findings. One of the patients had an abnormal a pulmonary function test with FVC: 50% and FEV1: 54%, indicating a restrictive pulmonary pattern. Spinal radiography evaluation showed mild scoliosis in two individuals. Genetic test revealed the variant c.122T>C (p.Ile41Thr) in a homozygous state in the FIG4 gene in all three patients. Despite being a rare variant of CMT, patients with disease causing variants in FIG4 usually have more severe forms, including potential respiratory involvement. Accurate genetic diagnosis is very important for appropriate genetic and reproductive counseling of patients.