Familial Hyperekplexia Caused by a Novel Homozygous SLC6A5 Variant: A Case Report

Hyperekplexia is a rare non-epileptic paroxysmal disorder characterized by a marked startle response and hypertonia to auditory, tactile, or visual sudden external stimuli. GLRA1, SLC6A5, GLRB, and ATAD1 gene pathogenic variants have been identified in these patients.

The girl was born 39+1 weeks and admitted to the neonatal intensive care unit with spasm-like contractions and followed by breath holding. Except for transient hyperammonemia, neurologic and metabolic tests were normal, and there was no seizure-like movement during hospitalization. In the 4th month of her life, the patient had spasm-like findings with stimulation, and the symptoms were controlled with clonazepam, considering hyperekplexia. Clinical exome sequencing revealed a previously undescribed homozygous variant [c.748T>C; p.(Ser250Pro) in exon 4] in the SLC6A5 (NM_004211.5) gene. Sanger sequencing confirmed the c.748T>C variant in the family: both parents were heterozygous carriers, while the brother was homozygous. Her sibling also had stimulus-induced crying and stiffness in infancy, but these resolved within months without treatment, and his developmental milestones have been age-appropriate.

This case highlights the importance of recognizing hereditary hyperekplexia in the differential diagnosis of neonatal seizures and supports the potential pathogenic relevance of the SLC6A5 c.748T>C (p.Ser250Pro) variant, particularly in benign, nonrecurrent cases with transient hyperammonemia from catabolic stress and glycine transporter dysfunction.