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


YILMAZ F. H., Kahraman A. B., DUYMUŞ F., Koçak Eker H., Çelik H., Büyükeren M., ...Daha Fazla

Molecular Syndromology, cilt.17, sa.3, ss.271-275, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 17 Sayı: 3
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1159/000547752
  • Dergi Adı: Molecular Syndromology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
  • Sayfa Sayıları: ss.271-275
  • Anahtar Kelimeler: Hyperekplexia, Newborn, Transient hyperammonemia, Case report
  • Sağlık Bilimleri Üniversitesi Adresli: Evet

Özet

Abstract – Introduction: 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. Case Report: 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. Conclusions: 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.