[Clinical and genetic analysis of three children with Hyperekplexia]

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Hyperekplexia is a rare neurological disorder characterized by exaggerated startle responses.
• Clinical manifestations include generalized stiffness and frequent falls.
• Genetic factors play a crucial role in the pathogenesis of Hyperekplexia.

Purpose of the Study:

• To investigate the clinical and genetic profiles of three pediatric patients diagnosed with Hyperekplexia.
• To identify novel genetic variants associated with Hyperekplexia.
• To evaluate the efficacy of clonazepam treatment in affected individuals.

Main Methods:

• Case study involving three children diagnosed with Hyperekplexia.
• Collection of clinical data, including neurological examinations.
• Whole exome sequencing (WES) for genetic variant identification.
• Sanger sequencing and bioinformatic analysis for variant validation.

Main Results:

• All three patients presented with exaggerated startle reflexes, stiffness, and falls.
• Two patients harbored homozygous variants in the GLRB gene, including a novel variant (c.1017_c.1018insAG).
• The third patient had compound heterozygous variants in the GLRA1 gene, with an unreported autosomal recessive inheritance pattern.
• All patients showed positive response to clonazepam treatment.

Conclusions:

• Hyperekplexia exhibits distinct clinical features that aid in early identification.
• Genetic analysis is essential for accurate diagnosis of Hyperekplexia.
• Early diagnosis and treatment, such as with clonazepam, can improve patient outcomes.