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GENATLAS PHENOTYPE
last update : 03-11-2015
Symbol STHE3
Location 11p15.1
Name Startle disease, hyperekplexia 3
Other name(s)
  • Stiff--Man syndrome congenital
  • Kok disease
    • Corresponding gene SLC6A5
    Main clinical features
  • hypertonia, exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnea episodes, greatly exaggerated startle responses, which were sometimes associated with falling, markedly hyperactive brainstem reflexes
  • can have serious consequences, including brain damage and/or sudden infant death
  • primary cause of startle disease is defective inhibitory glycinergic transmission
    • Genetic determination autosomal recessive
    Prevalence . second major cause of startle disease (PMID: 22700964)
    Function/system disorder neuromuscular
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   truncated protein leading to defective subcellular localization, decreased glycine uptake or both, with selected mutations affecting predicted glycine and Na(+) binding sites
    Remark(s)
  • the majority (over 90p100) of children with SLC6A5-linked hyperekplexia have recurrent neonatal apneas (PMID: 22700964))
  • pY705C (c.2114A→G) in transmembrane domain 11, show significant variation in clinical presentation: classical hyperekplexia symptoms, associated to abnormal respiration, facial dysmorphism, delayed motor development, or intellectual disability (PMID: 22753417))