Hyperekplexia is a genetic condition characterized by an exaggerated startle reaction to sudden loud sounds, movement, or touch. The muscles may stiffen as a result.

Hyperekplexia is a rare condition. More than 150 people worldwide have received a diagnosis of hyperekplexia. However, its exact prevalence is unknown.

Mutations in specific genes that affect how the nervous system reacts to glycine — a type of amino acid — can cause symptoms associated with hyperekplexia. Diagnosis typically requires looking for any gene alterations that affect how nerve cells react to glycine.

Misdiagnosis of the condition can prolong treatment. In some cases, doctors may confuse the condition with a form of epilepsy.

Keep reading to learn what hyperekplexia is, how to treat it, and which specific gene mutations can cause it.

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Hyperekplexia is a genetic neurological disorder. This condition primarily affects infants, and symptoms usually start to show shortly after birth.

When an infant with hyperekplexia hears a loud noise, it startles them more than is generally considered typical. They may also have this reaction to other unexpected stimuli, such as sudden movements or touch.

When startled, the infant becomes rigid and cannot move for a brief period. The rigidity can sometimes stop an infant from breathing and, in some cases, can be fatal.

An infant with hyperekplexia also has continual hypertonia, which means their muscles appear stiff and affect movement. It may lead to body spasms or eye movement problems.

There are two forms of the conditions, mild and major. Stress or anxiety may affect the intensity of the startle response.

Besides hypertonia and exaggerated startle response, infants with hyperekplexia may also experience:

  • arm or leg movements while asleep
  • hypnagogic myoclonus, which is when a muscle twitches while falling asleep
  • a forward extension of the head accompanied by arm, leg, and neck spasms when tapped on the nose

Also, this condition has associations with the following:

  • increased likelihood of fall or injury
  • developmental delays, which can affect a child’s performance at school
  • issues with breathing
  • abdominal hernias, which is when pressure causes a bulge in the lower stomach area
  • congenital hip dislocation, as a result of the ball and socket joint not developing properly
  • unstable walking

In rare cases, infants also have epilepsy, resulting in recurrent seizures.

Sudden infant death syndrome (SID) is the leading cause of death in infants between 1 month and 1 year old. Hyperekplexia may account for some cases of SID.

Can hyperekplexia occur in adulthood?

Signs and symptoms of hyperekplexia usually start to fade when an infant turns 1 year old.

However, for some people, the atypical startle reflex and periods of rigidity can persist throughout their life. The condition may also affect gait (how someone walks) and breathing.

Hyperekplexia is a genetic condition that occurs when mutations occur in specific genes. Genes are made up of DNA and provide instructions for protein making.

Researchers have found links between hyperekplexia and variants in the following genes:

  • ATAD1
  • GLRA1
  • GLRB
  • GPHN
  • SLC6A5

These genes play a role in producing proteins found in neurons (nerve cells) that affect how the cell responds to glycine. As well as being an amino acid, which combines to form more protein, glycine is a neurotransmitter. A neurotransmitter is a chemical messenger that acts on the nervous system.

In healthy individuals, glycine acts to regulate muscle fiber stimulation. Mutated nerve receptor proteins block glycine binding, causing muscles to overreact and other symptoms of hyperekplexia.

If a person has a mutation in any of the above genes, it can reduce the effect of glycine on the nervous system. Consequently, neurons transmit unregulated signals to the brain and the muscles, causing unintended muscle movements and an excessive startle reaction.

People may inherit hyperekplexia in an autosomal dominant or autosomal recessive pattern.

Autosomal dominant inheritance

This means that only one gene copy from one parent needs to have a mutation for the infant to have the disorder. The parent with that gene mutation likely has the same condition.

In the above example, an infant has a 50% chance of inheriting the gene variant and the disorder.

Autosomal recessive inheritance

This means that both gene copies (one from each parent) must have a mutation for the infant to have the disorder. If each parent has only one copy of the variant gene, they are both carriers but usually do not have symptoms.

In this example, the newborn has a 25% chance of inheriting the disorder, a 25% chance of inheriting no gene variants, and a 50% chance of becoming an asymptomatic carrier.

To diagnose hyperekplexia, doctors look for the three characteristic features of the condition:

  • generalized muscle stiffness immediately after birth
  • an exaggerated startle response to unexpected or sudden sensory inputs, such as loud sounds
  • a short period of generalized muscle stiffness during the startle response

Genetic testing can detect the five genetic variants that have links to hyperekplexia. However, routine and some specialized tests — such as those measuring brain activity — typically show “normal” results.

Misdiagnosing hyperekplexia

Misdiagnosis can be a problem in cases of hyperekplexia. For instance, one small study from 2017 found that 13 out of 16 participants had previously received an incorrect diagnosis of epilepsy.

A small, older study from 2014 — involving 17 Japanese children — found that only seven had received a correct diagnosis of hyperekplexia before the age of 1 year. However, all 17 infants displayed the characteristic muscle stiffness and atypical startle response shortly after birth.

The authors of this study emphasize the importance of receiving an early, correct diagnosis to receive appropriate treatment and prevent accidental injuries.

While diagnosis normally occurs in childhood, a case report from 2020 describes the diagnosis of a 63-year-old woman. She experienced symptoms including abnormal, excessive, and involuntary responses to harmless and unexpected sensory inputs, meeting the criteria for diagnosing hyperekplexia. However, genetic tests returned normal results.

Clonazepam, a tranquilizer in the benzodiazepine family, can treat the symptoms of hyperekplexia. This medication can reduce muscle stiffness in affected newborns following the atypical startle response. Experts recommend a daily dose of 0.01 to 0.1 milligrams (mg) per kilogram (kg) for children and 0.8 mg per day for adults.

Other possible medications for treating hyperekplexia, which involve a range of antianxiety and antispastic drugs, include:

  • carbamazepine (Carbatrol)
  • clobazam (Onfi)
  • phenytoin (Dilantin)
  • diazepam (Valium)
  • valproate (Depacon)
  • 5-hydroxytryptophan
  • piracetam
  • phenobarbital

Physical and cognitive therapy might help lessen the fear of falling and improve walking.

The Vigevano maneuver, which involves flexing the head and legs toward the torso, can be lifesaving. This technique may help prevent an infant from turning blue if they stop breathing due to muscle stiffness associated with hyperekplexia.

Hyperekplexia is an inherited nervous system disorder that usually first presents shortly after birth. Infants with the condition have an excessive startle reaction to unexpected stimuli, including loud noises.

They also have stiff muscles at all times except when asleep. Infants may go rigid during the exaggerated startle response, which can be fatal if it occurs for a prolonged time.

Diagnosis usually requires genetic testing that looks for the presence of mutations.

Treatment is available. Clonazepam (a type of benzodiazepine) can help lessen the symptoms, which usually begin to fade after 1 year of life.