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Abstract Details

A Novel SPG11 mutation causing Charcot- Marie-Tooth Disease Type 2
Neuromuscular and Clinical Neurophysiology (EMG)
P14 - Poster Session 14 (8:00 AM-9:00 AM)
1-012
NA
Mutations in SPG11 gene are known to cause autosomal recessive hereditary spastic paraplegia (ARHSP), ALS, and Charcot-Marie-Tooth (CMT) disease type 2. We present a case of CMT2 caused by a novel SPG11 mutation not yet described to produce this phenotype.

Ms. J.O. is a 34-year-old woman of Peruvian decent who presented with gait disturbance since the age of 10 years. This was followed by upper extremities weakness (distally then proximally) and by the age 25 she was wheel-chair dependent. Her motor milestones had been mildly delayed, and she attended Special education school. She was adopted and her family history was unknown. Her examination revealed cognitive impairment and normal cranial nerves. Her Lower extremities (LE) were hypotonic and she had scoliosis. The distribution of atrophy and weakness was distal > proximal, LE>UE. Reflexes were depressed and she had distal hypoesthesia. Her clinical presentation was consistent with length dependent neuropathy. 

Her routine blood tests were normal. Electrodiagnostic studies demonstrated severe sensory-motor axonal neuropathy with preserved conduction velocities. MRI-brain showed severe thinning of corpus callosum and bilateral frontal periventricular hyperintensities (“ear of lynx” sign).  Next Generation sequencing identified a homozygous nonsense mutation in the SPG11 gene (chromosome 15): NM_025137.3:c.3121C>T; p.Arg1041Ter.  
SPG11 gene, also known as KIAA1840 / ALS5 encodes spastacsin, a protein involved in neuronal axonal growth and intracellular transport. To date, more than 100 pathogenic mutations of SPG11 causing ARHSP, ALS and CMT2 have been described. The mutation found in our patient has been implicated in 3 cases of ARHSP with thin corpus callosum, but not with other phenotypes. This is the first case of CMT caused by above SPG11 mutation.
This case represents an SPG11 variant syndrome consistent with CMT2 yet associated with a novel pathogenic mutation. Pleiotropy of this gene producing different phenotypes is again demonstrated.  
Authors/Disclosures
Nirav Sanghani, MBBS (St. Francis Hospital and Medical Center)
PRESENTER 		Dr. Sanghani has nothing to disclose.
Leila Maybodi, MD No disclosure on file
Nizar Souayah, MD, FÂ鶹´«Ã½Ó³»­ (NJMS) Dr. Souayah has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. Dr. Souayah has received publishing royalties from a publication relating to health care.