P3.19 Neonatal presentation of Charcot-Marie-Tooth disease: A new mutation in Mitofusin 2 gene

Abstract

Charcot-Marie-Tooth (CMT) is a heterogeneous group of inherited peripheral neuropathies with a prevalence of 1/ 2500. The Mitofusin 2 has an essential role in axonal transport of mitochondria, as well as in controlled fusion of its membrane, so there are frequent changes of some mitochondrial respiratory chain complexes (I, II, III, V). Young boy 3 years old without a family history of neuromuscular disease. In the neonatal period he had a marked hypotonia and swallowing difficulties. At 7 months he was referred for consultation for motor delay. Clinical examination revealed flaccid tetraparesis predominantly distal in lower limbs with axial involvement. No heart disease and no respiratory compromise and a preserved bulbar function. The electromyographic study showed a severe axonal neuropathy. The brain MRI revealed white matter alterations in both semi-oval centers. The electroencephalogram (EEG) was immature, poorly structured with paroxysmal activity during sleep. Molecular analysis of the gene MFN2 revealed a de novo pathogenic missense mutation in the vicinity of the GTPase domain, very close to a well known mutational hotspot, c.272T> A (p.Val91Glu) in exon 4, in heterozygosity, not found in the parents. The authors present an atypical form of CMT2A2 with a mutation in the gene MFN2 not previously described, which broadens the clinical and molecular spectrum of the rare HMSN2A.