SYT2-Related Disease: A Case-Based Review.

Area of Science:

• Neurology
• Genetics
• Molecular Biology

Background:

• Synaptotagmin-2-related disease is an ultrarare disorder affecting neuromuscular junctions.
• Mutations in the SYT2 gene, particularly in the C2B domain, are linked to this condition.
• Clinical manifestations include distal lower limb muscle atrophy, foot deformities, and neonatal hypotonia.

Purpose of the Study:

• To review the clinical, electrophysiological, and pathological aspects of Synaptotagmin-2-related disease.
• To characterize the phenotypic spectrum of SYT2-related disease.
• To highlight the features of this neuromuscular junction disease, considered a distal hereditary motor neuropathy.

Main Methods:

• Literature review of 27 previously reported cases.
• Detailed description of a novel, previously unreported SYT2 variant.
• Analysis of clinical, electrophysiological (EMG), and genetic (next-generation sequencing) data.

Main Results:

• A 14-year-old male presented with neonatal hypotonia, dysphonia, recurrent infections, delayed motor development, and glaucoma.
• Electromyography (EMG) revealed reduced compound muscle action potential and myopathic findings.
• Genetic analysis identified a homozygous variant in the SYT2 gene.

Conclusions:

• The study provides a comprehensive characterization of the SYT2-related disease phenotype.
• Electrophysiological and pathological features are crucial for diagnosis.
• The findings contribute to understanding this rare neuromuscular disorder.