G.P.89 Early onset mitofusin 2 gene (MFN2) mutation: Report of eight patients

Abstract Mutations in the mitofusin 2 gene (MFN2), encoding an outer mitochondrial membrane protein of the dynamin family GTPase, cause mainly Charcot–Marie–Tooth 2A (CMT2A), hereditary motor and sensory neuropathy type VI (HMSN VI) and axonal neuropathy with spastic paraparesis. Hereby, we report eight genetically confirmed patients with MFN2 defects. The mean current age of the patients is 14.5 years, (range 4–28), three are male and five female. A dominant familial inheritance was confirmed in two cases while six are sporadic. All patients were submitted to neurological, electrophysiological, ophthalmological and cranial MRI evaluation.. Symptoms started in all patients within the two first years of life with falls, and difficulties to walk consisting in: flat foot (4), equinovarus foot position (3), stepage (7) and spastic paraparesis (1). Distal upper limb involvement was observed in all patients, being severe in four. Two patients developed diaphragmatic paresis and one vocal cord paresis. Learning difficulties were observed in four and one manifested disartic episodes that lasted several days. Two patients were chair bound at 12 years old requiring nocturnal non invasive ventilatory support (BIPAP). The remaining of the patients were able to walk with orthesis (DAFOS). Axonal neuropathy was identified in all the patients. We also discuss cranial MRI, visual evocated potentials (VEP), genetic and ophthalmological findings. Early onset mitofusin deficiency constitutes a severe and disabling condition. Because several organs may be involved, systemic evaluation and follow up is required, especially when respiratory function is compromised.