Hereditary Hyperekplexia, also known as startle disease, is a rare neurogenetic condition that affects the way the nervous system controls muscle movement and responses to sudden stimuli. Individuals with this condition experience an exaggerated startle reflex – a sudden, involuntary jerk or stiffness triggered by unexpected sounds, touches, or movements. While the startle reflex is normal in all humans, in people with Hereditary Hyperekplexia it is heightened and prolonged, often causing falls, stiffness, or temporary immobility.
What Causes Hereditary Hyperekplexia?
Hereditary Hyperekplexia is caused by genetic changes that disrupt communication between nerve cells in the brain and spinal cord. Most commonly, the condition is associated with disease – causing gene changes in the GLRA1 gene, which provides instructions for making a protein called the glycine receptor alpha-1 subunit. This protein plays a critical role in inhibitory signalling within the central nervous system. Mutations in other genes, such as SLC6A5, GLRB, GPHN, or ARHGEF9, can also cause the condition, though these are less common.
The condition is typically inherited in an autosomal dominant or autosomal recessive manner, meaning that it can occur when one or both copies of the gene are altered, depending on the gene involved. Genetic counselling and testing can help families understand their inheritance pattern and risk of recurrence.
Signs and Symptoms
Hereditary Hyperekplexia usually presents from birth. Newborns may show generalised stiffness (hypertonia) and exaggerated startle responses to everyday stimuli. During a startle episode, a baby or child may suddenly stiffen and fall like a “log” without losing consciousness. These episodes can be distressing and potentially dangerous, especially if they lead to injury from falls.
In infants, the condition can sometimes be mistaken for epilepsy because of the sudden jerking movements. However, hyperekplexia does not typically involve abnormal brain activity seen in seizures. In most cases, stiffness improves as the child grows older, but the exaggerated startle reflex often persists into adulthood.
Diagnosis and Genetic Testing
Diagnosis is based on clinical features, family history, and genetic testing to identify mutations in the associated genes. Early and accurate diagnosis is crucial, as it allows appropriate management and helps prevent complications. Genetic testing through a neuromuscular or movement disorder gene panel can confirm the diagnosis and inform family planning decisions.
At Rosalind Genetics, we work with families and clinicians to provide access to comprehensive genetic testing and expert genetic counselling. Understanding the genetic basis of hyperekplexia can help clarify prognosis, guide treatment, and identify other at-risk relatives.
Treatment and Management
Treatment focuses on reducing startle episodes and improving quality of life. Medications such as clonazepam, which enhances inhibitory signalling in the brain, are often effective in controlling symptoms. Safety strategies, such as fall prevention and avoiding known triggers, are also important. Early intervention and supportive care can significantly improve outcomes for affected individuals.
Hereditary Hyperekplexia is a rare but manageable genetic condition. With advances in molecular diagnostics and personalised medicine, families now have access to more accurate testing and better-informed care options.
If you or a family member have symptoms suggestive of hereditary startle disease, speak with a healthcare professional or contact Rosalind Genetics to learn more about our testing and counselling services.
