Phenotypical spectrum of SACS variants: Neuromuscular perspective of a complex neurodegenerative disorder

Objectives Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by the SACS gene variants. Main clinical features include early-onset and progressive cerebellar ataxia, spasticity, sensorimotor polyneuropathy. However, the phenotypic spectrum expanded with the increased availability of next-generation sequencing methods. Materials and Methods Herein, we describe the clinical features of nine patients from seven unrelated families with SACS variants from the cohort of the Neuromuscular Disorders Unit of the Neurology Department of the Istanbul University, Istanbul Faculty of Medicine. Results Seven patients were male. Seven patients in our cohort had disease onset in the first decade of life. Eight patients were born to consanguineous marriages. Distal weakness in the lower limbs was a prominent feature in all of our patients. Seven patients had ataxia, and six patients had spasticity. Interestingly, one patient showed an isolated Charcot-Marie-Tooth-like phenotype. Five patients showed sensorimotor demyelinating polyneuropathy in the nerve conduction studies. Linear pontine hypointensity was the most frequent cranial magnetic resonance imaging (MRI) abnormality. Two patients with a later disease onset had a homozygous c.11542_11544delATT (p.Ile3848del) variant. The rest of the identified variants were scattered throughout the SACS gene. Conclusions Atypical clinical features in our patients highlight that the phenotypic spectrum of ARSACS can be observed in a wide range.