G.P.88 Peripheral neuropathies caused by mutations in the myelin protein zero

Abstract

Abstract Charcot–Marie–Tooth disease (CMT), is a group of clinically and genetically heterogeneous neuropathies divided into demyelinating (CMT1) and axonal forms (CMT2). Mutations in the myelin protein zero (MPZ/P0) gene are the third most frequent cause of CMT. This gene is a member of the immunoglobulin gene superfamily that encodes the most abundant protein of the peripheral myelin, necessary for myelin compaction. There are many mutations in MPZ, most of them cause the CMT1B phenotype with normal early development but disability appears during the first two decades of life; and others, are responsible for severe neuropathies of infancy designated as Dejerine–Sottas syndrome. MPZ mutations have also been shown also in axonal type of CMT2. Hereby, we report the clinical and electrophysiological features of eight patients belonging to eight families affected by CMT 1B. The mean age of the patients is 13 years (range: 4–29). In five patients, the symptoms appeared between 2 and 3 years of age, showing motor clumsiness, difficulty to rise from the floor and for climbing stairs. In two cases, debuted before age of two, with a delay to develop an autonomous gait. The other one, presented an atypical phenotype at the age of seven, with hand tremor and episodes of muscular pain after exercising, with an intermittent increase of the CPK. Most of the patients had a stable evolution; five of them developed scoliosis and had affected their upper extremities. Only one of the patients developed a proximal weakness, and required scoliosis surgery at the age of 13. The electrophysiological study, showed a demyelinating neuropathy in all of the cases. Two patients with the same mutation, C241A, had different clinical evolution. There is a wide clinical spectrum in patients with MPZ gene mutation, which makes difficult to establish a genotype-phenotype correlation. We recommend the study on MPZ gene in patients with demyelinating neuropathy (once mutations in the PMP22 gene have been ruled out).