To study the clinical, genetic, and electrophysiological findings in patients with Hereditary Spastic Paraplegia (HSP).

HSP encompasses a clinically and genetically heterogenous set of neurodegenerative diseases with 80 identified subtypes. HSP is classified as pure HSP (pHSP) and complex HSP (cHSP) with pHSP characterized by lower extremity weakness and spasticity, gait difficulty, upper motor neuron signs, and bladder dysfunction and cHSP in addition to pHSP findings has dementia, intellectual disability, epilepsy, and peripheral neuropathy.

Retrospective electronic medical record review of genetic confirmed HSP cases followed in the pediatric and adult Neuromuscular Clinics from 2013-2020. Clinical presentation, family history, examination, electrodiagnostic data, neuroimaging, co-morbidities and treatment was recorded.

Twenty-two patients (13 males, 9 females) mean age 34 years (range 8-73) were included. Genetically confirmed etiologies (n=20) included SPAST 40% (n=8), SPG7 15% (n=3), KIF1A 15% (n=3), KIF5A 5% (n=1), REEP1 5% (n=1), MTP-ATP6 5% (n=1), MARS 5% (n=1), ZFYVE26 5% (n=1), SACS 5% (n=1). Symptom onset to genetic confirmation on average was 12 years (1-51 years). Eighty percent (n=18) presented with gait difficulty, 59% (n=13) were ambulatory, sensory motor axonal polyneuropathy 36% (n=8), scoliosis/musculoskeletal deformities 27% (n=6), cognitive impairment 23% (n=5), dysarthria 18% (n=4), seizures 18% (n=4), cerebellar atrophy on MRI 13.6% (n=3), attention difficulty 9% (n=2), visual impairment 9% (n=2), and hearing impairment 9% (n=2). Fifty-five percent (n=12) received a baclofen pump.

Our study demonstrates that SPAST was the most common disease-causing gene mutation followed by SPG7 and KIF1A.  Gait difficulty, scoliosis, sensory motor axonal polyneuropathy and neurocognitive comorbidities were common in our cohort particularly amongst patients with KIF1A mutations and other cHSP subtypes. Study limitation includes single center experience with small study population.