Clinical and genetic features of SPG11: A single center experience

Abstract

Objective: To investigate the clinical and genetic characteristics of the patients with Spastic Paraplegia 11 (SPG11). Background: SPG11 is the most frequent subtype of the recessively inherited hereditary spastic paraplegias (HSP). Caused by the mutations in the SPG11 gene, the disease usually results in a complex phenotype, characterized by intellectual disability, dopa-responsive dystonia, and motor neuropathy accompanied by spasticity in the lower limbs. Design/Methods: We retrospectively evaluated the clinical and genetic features of the 7 patients from 6 unrelated families, diagnosed with SPG11 at the Neuromuscular Unit, Neurology Department, Istanbul Faculty of Medicine, Istanbul University, between 2010 and 2019. Mutations in SPG11 were identified by whole exome sequencing (WES). Results: Five patients were male. Mean age at onset was 18.85±5.42 (ranges 13–26 years). All patients, except one with a compound heterozygous mutation, were born to consanguineous marriages. Family history was positive in three probands. All patients had spasticity in the lower limbs. Neuropsychological tests were performed in four patients, and three of them showed signs of intellectual disability. One patient had sensorineural hearing loss, and one had task specific dystonia. One patient had horizontal and vertical nystagmus and another patient had opthalmoparesis accompanied by dysarthria. Interestingly, her sibling did not have these clinical features. Four patients had findings in the EMG consistent with anterior horn disease and one patient showed signs of sensorimotor polyneuropathy. EMG findings were normal in the other patients. Four patients had thin corpus callosum. One patient had hydrocephalus, hydromyelia and tethered cord. Cerebrospinal fluid (CSF) protein was elevated in one patient. Conclusions: Our study highlighted that the phenotypic spectrum of SPG11 can be observed in a wide range. Revealed mutations may enlighten the hot-spot regions of the SPG11 gene in the Turkish population.