National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Hereditary hyperekplexia

Información en español


Other Names:
Startle disease, familial; Startle reaction, exaggerated; Exaggerated startle reaction; Startle disease, familial; Startle reaction, exaggerated; Exaggerated startle reaction; STHE; Stiff-baby syndrome; Stiff-man syndrome, congenital; Stiff-person syndrome, congenital; Kok disease; Hyperexplexia hereditary See More
Categories:
Hereditary hyperekplexia is a nervous system disorder (neurological disorder), that is usually noticed shortly after birth. Symptoms in a newborn include generalized muscle stiffness while awake (hypertonia) and exaggerated startle reflex to unexpected loud noises, visual stimuli, or touch. Following the startle reaction, infants experience a brief period in which they are very rigid and are unable to move. During these rigid periods, some infants may stop breathing (apnea), which can be fatal and has been associated with sudden infant death syndrome (SIDS). Muscle stiffness usually fades completely during the first few years of life. However the exaggerated startle reflex and periods of rigidity may continue throughout a person's life. Depending on the severity of the continued symptoms, a child or adult with hereditary hyperekplexia may have an increased risk of falling or otherwise injuring themselves. In some cases, children with hereditary hyperekplexia may have mild developmental delays.[1][2][3] Abdominal hernias and congenital dislocation of the hip have also been associated with hereditary hyperekplexia.[2][3]

Diagnosis of hereditary hyperekplexia requires the three main features: generalized stiffness immediately after birth, excessive startle reflex to unexpected stimuli, and a short period of generalized stiffness following the startle response.[2][4] Of note, the results of routine blood tests, urinalysis, brain imaging studies, or EEG are usually normal.[1][2][3] Hereditary hyperekplexia has different inheritance patterns and is associated with changes (mutations) in at least five genes. Genetic testing is available to detect the genetic changes.[1][2][3][4] Clonazepam is the most commonly used treatment and successfully reduces symptoms in most people.[1][2][3]
Last updated: 11/8/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 28 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Ataxia 0001251
Esophagitis
Inflammation of the esophagus
0100633
Fasciculations
Muscle twitch
0002380
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ] 		0002020
Hiatus hernia
Stomach hernia
0002036
Hyperreflexia
Increased reflexes
0001347
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Muscle stiffness 0003552
Myoclonus 0001336
Rigidity
Muscle rigidity
0002063
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
30%-79% of people have these symptoms
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Sleep disturbance
Difficulty sleeping
Trouble sleeping
[ more ] 		0002360
Umbilical hernia 0001537
5%-29% of people have these symptoms
Hip dislocation
Dislocated hips
Dislocation of hip
[ more ] 		0002827
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Seizure 0001250
Percent of people who have these symptoms is not available through HPO
Apnea 0002104
Aspiration 0002835
Autosomal dominant inheritance 0000006
Autosomal recessive inheritance 0000007
Exaggerated startle response 0002267
Frequent falls 0002359
Hypertonia 0001276
Hypokinesia
Decreased muscle movement
Decreased spontaneous movement
Decreased spontaneous movements
[ more ] 		0002375
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Inguinal hernia 0000023
Nocturnal seizures 0031951
Showing of 28 |
Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Hereditary hyperekplexia is commonly treated with the anti-anxiety and anti-spastic drug clonazepam. Other medications which have been helpful for some people include carbamazepine, phenytoin, diazepam, valproate, 5-hydroxytryptophan, piracetam, phenobarbital, and fluoxetine.[3][4][5][6] In some cases, a combination of treatments (i.e. clobazam and clonazepam) may be needed.[6][7]

If fear of falling has limited a person's willingness to go outside their home and/or caused the development of a cautious walking style, cognitive behavior therapy (CBT) and/or physical therapy, in combination with the medication to control the startle reflex and rigidity period, may help reduce anxiety, improve confidence in walking, and improve the person's quality of life.[3][4][5]
Last updated: 11/8/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
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.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Hereditary hyperekplexia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Hereditary hyperekplexia. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary hyperekplexia. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I have been diagnosed with hyperekplexia. When I am startled, my right leg stiffens, causing me to fall. My doctor put me on Clonazepam, which worked at first, but now my symptoms have returned. Can you tell me what other medications might be used to treat this condition? See answer


  1. Masri A, Chung SK, Rees MI. Hyperekplexia: Report on phenotype and genotype of 16 Jordanian patients. Brain Dev. April 2017; 39(4):306-311. https://www.ncbi.nlm.nih.gov/pubmed/27843043.
  2. Mine J, Taketani T, Yoshida K, et al. Clinical and genetic investigation of 17 Japanese patients with hyperekplexia. Dev Med Child Neurol. April 2015; 57(4):372-77. https://www.ncbi.nlm.nih.gov/pubmed/25356525.
  3. Lee Y, Kim NY, Hong S, et al. Familiar Hyperekplexia, a Potential Cause of Cautious Gait: A New Korean Case and a Systematic Review of Phenotypes. Journal of Movement Disorders. January 2017; 10(1):53-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288664/.
  4. Tissen MAJ & Rees MI. Hyperekplexia. Gene Reviews. October 4, 2012; http://www.ncbi.nlm.nih.gov/books/NBK1260/.
  5. Haruno L. Hyperekplexia. National Organization for Rare Disorders (NORD). 2013; http://rarediseases.org/rare-diseases/hyperekplexia/.
  6. Mineyko A, Whiting S, Graham GE. Hyperekplexia: treatment of a severe phenotype and review of the literature. Can J Neurol Sci. 2011 May; 38(3):411-6. http://www.ncbi.nlm.nih.gov/pubmed/21515498.
  7. McAbee GN. Clobazam-clonazepam combination effective for stimulus-induced falling in hyperekplexia. J Child Neurol. 2015 Jan; 30(1):91-2. http://www.ncbi.nlm.nih.gov/pubmed/24453146.