To report a novel case of FOSMN associated with mutation in C9orf72 gene.

FOSMN is a rare neurological syndrome. It has a characteristic pattern of progression starting with sensory disturbance in the trigeminal territory followed by craniocaudal spread of sensory loss and weakness. The exact pathophysiology of FOSMN is unclear, however, neurodegenerative and autoimmune mechanisms have been proposed.

A 30-year-old woman presented with two years of progressive left face numbness which spread to left trunk, followed by progressive bilateral upper extremity numbness and weakness, and bilateral leg weakness. Her initial exam was notable for hypoesthesia in left V1/V2 distribution, spasticity in all extremities, distal more than proximal weakness in arms and legs, diffuse hyperreflexia and atrophy in bilateral hands. 

Initial EMG showed active denervation with reinnervation in C7-T1 muscles. Vitamin B12, vitamin E, copper, TSH, ANA, ENA were normal. Serology was negative for VZV, celiac, HTLV I/II and Lyme. Ganglioside antibodies, Mayo clinic neuronal and paraneoplastic antibody panels, MRI C-spine and CSF studies were unremarkable. MRI brain demonstrated bilateral corticospinal tract degeneration.

She was empirically treated with steroids with subjective improvement in speech, dexterity and balance. However, her extremity weakness progressed and she developed dysarthria and dysphagia.  Genetic analysis showed expansion of >30 hexanucleotide repeats in one copy of the C9orf72 gene, subsequently found in her biological father. No pathogenic mutation was noted in SOD1, TARBDP, CHCHD10, VCP, SQSTM1, PABPN1 genes. 

FOSMN is a progressive neurological syndrome. Even though autoimmune mechanisms have been proposed, the pathological studies showing TDP-43 inclusions and association with superoxide dismutase-1 (SOD-1) gene mutation favor a neurodegenerative mechanism. We report a novel case of FOSMN with C9orf72 mutation. This supports that some cases of FOSMN are neurodegenerative and on the motor neuron disease spectrum.  This case also highlights a unique phenotype associated with C9orf72 mutation.