Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

*
(*) mandatory field





 

Other search option(s)

Hereditary hyperekplexia

Orpha number ORPHA3197
Synonym(s) Congenital stiff man syndrome
Familial startle disease
Hereditary hyperexplexia
Hyperekplexia
Kok disease
Stiff baby syndrome
Prevalence <1 / 1 000 000
Inheritance
  • Autosomal dominant
  • Autosomal recessive
Age of onset Neonatal/infancy
ICD-10
  • G25.8
OMIM
UMLS -
MeSH -
MedDRA -
SNOMED CT -

Summary

Hereditary hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses.

To date about 150 cases have been reported in the literature.

Hereditary hyperekplexia manifests shortly after birth with violent jerking to noise and touch, and massive and sustained stiffening of the trunk and limbs, clenching fists, and attacks of a high-frequency trembling. Newborns are at risk for sudden infant death due to laryngospasm and cardiorespiratory failure. Stiffness attacks may resemble epileptic seizures, although sleep can reduce or even abolish stiffness and jerking and EEG is normal. In the months after birth, muscle stiffness subsides, but excessive jerking to external stimulation or excitement persists. Motor milestones are often mildly delayed, but intellectual development is usually normal. Affected children walk toddling, and often seek assistance or a hold. Gait disturbance increases when in a hurry, amongst a crowd, or if forced. Stumbling or an unexpected jolt may induce uncontrolled falls (''like a log'') with the risk of serious injuries.

Mutations in the GLRA1 gene (5q32) are found in about 30% of patients with hereditary hyperekplexia (and a considerable number of patients without an obviously affected parent). These mutations are transmitted as an autosomal dominant or recessive trait. The GLRA1 gene encodes the alpha1 subunit of the juvenile neuronal receptor for the inhibitory neurotransmitter, glycine. Mutations of this subunit cause a variety of dysfunctions of the neuronal chloride (Cl-) channel, and therefore hereditary hyperekplexia is regarded as a channelopathy. Mutations in the GLRB, GPHN and SLC6A5 genes (4q31.3, 14q24 and 11p15.2-p15.1) have also been observed.

Diagnosis is based on the clinical signs, molecular genetic testing and electrophysiology.

Differential diagnoses include symptomatic hyperekplexia and spasticity, and epilepsy in perinatal brain damage and metabolic brain diseases, which can be excluded by normal EEG and reduction or abolition of stiffness and jerking with sleep.

Symptomatic treatment in adults involves clonazepam (1mg per day). In children lower doses are required. Vigabatrin is ineffective. Children gain benefit from repeated trials of physical exercise rather than from established physiotherapies or from resolute or demanding training. Extensive activities on soft or sandy ground are particularly effective. Intervention against incomprehension, mockery or pressure from uninformed teachers, relatives and friends may be required.

In most patients, fear of falling and the toddling gait normalizes in adolescence. However, brisk startle and jerkiness to unexpected stimulation persist lifelong, and a minority of patients suffer phobic anxiety of crossing open spaces and an insecure and hesitating gait disorder.

Expert reviewer(s)

  • Pr Hans-Michael MEINCK

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.


Captcha image

Detailed information

Clinical genetics review
  • EN (2012)
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.