Heterozygous D90A-SOD1 mutation in a patient with facial onset sensory motor neuronopathy (FOSMN) syndrome: a bridge to amyotrophic lateral sclerosis

Objective To describe a patient with facial onset sensory motor neuronopathy (FOSMN) syndrome associated with a heterozygous D90A mutation in superoxide dismutase (SOD1) gene. Methods The patient underwent neurological and neurophysiologic examinations, including blink and jaw reflexes, sural nerve and skin biopsies, and analysis of TARDBP, FUS and C9ORF72 genes. Results Neurological examination showed diffuse fasciculations, bulbar signs, hypotrophy and weakness of facial, neck, shoulder girdle and first interosseus muscles, and absent corneal reflex. Neurophysiologic studies demonstrated abnormal blink and jaw reflexes and reduced sensory nerve action potentials at upper limbs. Sural nerve and skin biopsies revealed mild loss of large and small nerve fibres. Genetic analysis demonstrated a heterozygous D90A-SOD1 mutation. Conclusions FOSMN syndrome has been recently described in patients with slowly progressive bulbar and upper limb amyotrophy. Sensory symptoms, mainly involving the trigeminal territory, typically precede the onset of motor weakness by months or years. The pathogenesis of FOSMN syndrome is unknown and possible immune-mediated mechanisms have been claimed. Our findings support the hypothesis that FOSMN syndrome is a primary degenerative disorder that widens the spectrum of motor neuron diseases.