Investigators at Swansea University and other centers in the UK, Australia, and Belgium studied the genotype-phenotype correlations in 97 individuals with a clinical diagnosis of hyperekplexia; 61 cases had mutations in GLRA1, 24 cases in SLC6A5 and 12 in GLRB. All gene-positive cases presented in the neonatal period and clonazepam was effective treatment in 95%. Hyperekplexia is a predominantly recessive inheritance, and is dominant in 16%. In 35 gene-negative cases, presentation was after the first month of life.
The characteristic symptoms of hyperekplexia are ‘stiffness, startles and stumbles.’ In addition, 50 of 89 patients had apnea attacks and 47 of 92 were developmentally delayed. Recurrent infantile apneas occurred more frequently in patients with SLC6A5 mutations than in those with GLRA1 mutations. Developmental delay occurred more frequently in patients with GLRB and SLC6A5 mutations than in those with GLRA1 mutations; 92% of GLRB cases had a mild to severe delay in speech acquisition. The developmental delay especially in speech may represent failure of developmental neural networks or migration defects. 
COMMENT. Hyperekplexia was first described by Kok O, and Bruyn GW  in 29 members of one family and occurred as a dominant autosomal transmission. Hypertonia is present at birth and becomes less pronounced during the first year of life but later leads to repeated falls. The name “hereditary stiff baby syndrome” was used by Lingam S, et al. . The child has a fixed stare and an expression of anxiety. Hypertonia diminishes during sleep and increases with the slightest psychic or tactile stimulus. Nose tapping elicits the hyperekplexic response and is included in the neonatal exam of infants at risk. Attacks of hypertonia that involve the respiratory muscles can lead to apneas that endanger life. The EMG shows persistent activity abolished by diazepam or clonazepam; the EEG is normal.
Early genetic testing is recommended for symptomatic hyperekplexic neonates and possibly preconception counseling for those at risk for GLRB and SLC6A5 mutations. Recessive inheritance of hyperekplexia is associated with an increased risk of learning difficulties and developmental delay, particularly in speech acquisition. Severe recurrent neonatal apneas occur in approximately 50% of cases, particularly those with mutations in GLRB and SLC6A5. Stiffness, startle and stumble are the cardinal features of hyperekplexia.