Abstract Details

Title Expanding the phenotypical spectrum of SACS mutation: A Single Center Experience

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 083

Objective To describe the clinical and genetic characteristics of the patients with autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).

Background ARSACS is an autosomal recessive disorder caused by the mutations in the SACS gene. The disease is characterized by a combination of early-onset and progressive cerebellar ataxia, spasticity, sensorimotor polyneuropathy. However, atypical clinical features are reported.

Design/Methods Herein, we evaluated the clinical and genetic features of the 9 patients from 7 unrelated families with SACS mutation at the Neuromuscular Unit, Neurology Department, Istanbul Faculty of Medicine, Istanbul University, between 2005 and 2020.

Results Seven patients were female. Seven patients in our cohort had disease onset in the first decade of life with delayed motor milestones. One patient had an onset at the age of 10 with distal weakness and foot deformities. Eight patients were born to consanguineous marriages. Family history was positive in three probands. 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 in our cohort showed an isolated Charcot-Marie-Tooth-like phenotype. Eight patients showed sensorimotor demyelinating polyneuropathy in the nerve conduction studies. Cranial magnetic resonance imaging (MRI) demonstrated linear pontine hypointensities in 8 patients and cerebellar atrophy in four patients. Prominent retinal nerve fibers were found in 5 patients. Optical coherence tomography (OCT) was performed in 7 patients, and 6 showed increased retinal nerve fiber layer thickness. Two patients had c.11542_11544delATT (p.Ile3848del) mutation. The rest of the identified mutations in our patients were scattered throughout the SACS gene. Strikingly, one of our patients’ brother with polyneuropathy, had a homozygous mutation in the VPS13D gene.

Conclusions Atypical clinical presentations in our patients highlighted that the phenotypic spectrum of ARSACS can be observed in a wide range. Genetic heterogeneity was a remarkable feature in our cohort.

Authors/Disclosures
Arman Cakar PRESENTER	Arman Cakar has nothing to disclose.
Meltem Inci II, MD (Istanbuil University Faculty of Medicine Department of Neurology)	Dr. Inci has nothing to disclose.
	No disclosure on file
Hacer Durmus, MD (Department of Neurology, Istanbul Faculty of Medicine)	Dr. Durmus has nothing to disclose.
	No disclosure on file

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Abstract Details