Uncontrollable Startle Reflex: Description, signs, and triggers
Hyperekplexia, a genetic neurological disorder, can present challenges beyond the first year of life. This condition, characterised by persistent exaggerated startle responses and brief periods of generalised stiffening or shaking, can lead to motor difficulties and cognitive effects if left untreated.
Diagnosis of hyperekplexia beyond infancy requires the observation of three key features: an exaggerated startle reflex to auditory or tactile stimuli, immediate stiffening or brief shaking episodes with rapid recovery to normal state, and motor development that may be delayed or impaired in severe cases. Cognitive function, however, is generally normal, especially with early diagnosis and treatment.
The primary treatment option beyond infancy is pharmacological therapy, primarily with clonazepam, a benzodiazepine that enhances GABA_A receptor activity to reduce neuronal hyperexcitability and startle reflex intensity. Other medications like valproic acid or carbamazepine may be used off-label, but their use is less common.
Avoidance of known startle triggers and physical safety precautions to prevent injury from falls or stiffening episodes are also crucial. In rare or severe forms, multidisciplinary care including neurologists, geneticists, and therapists is recommended.
Key clinical features beyond infancy include the exaggerated startle reflex, motor development delays or impairments in severe cases, and normal cognitive function with early diagnosis and treatment. Episodes may diminish in severity with age but can remain disabling if untreated.
Hyperekplexia is caused by mutations in specific genes, such as ATAD1, GLRA1, GLRB, GPHN, and SLC6A5. These genes play a role in producing proteins found in neurons that affect how the cell responds to glycine, a neurotransmitter. Genetic testing can detect the five genetic variants linked to hyperekplexia, but routine and some specialized tests may show "normal" results.
It's important to note that misdiagnosis can occur, with some cases being initially misdiagnosed as epilepsy. Clonazepam, a tranquilizer in the benzodiazepine family, is used to treat hyperekplexia and can reduce muscle stiffness in affected individuals. Other medications used to treat hyperekplexia include carbamazepine, clobazam, phenytoin, diazepam, valproate, 5-hydroxytryptophan, piracetam, and phenobarbital.
Physical and cognitive therapy may help lessen the fear of falling and improve walking in individuals with hyperekplexia. The condition may also affect gait and breathing in adulthood. The head lift maneuver, which involves flexing the head and legs toward the torso, can be lifesaving for infants with hyperekplexia who stop breathing due to muscle stiffness.
Inheritance of hyperekplexia can occur in either an autosomal dominant or autosomal recessive pattern. In autosomal recessive inheritance, both gene copies (one from each parent) must have a mutation for the infant to have the disorder. In autosomal dominant inheritance, only one gene copy from one parent with a mutation is necessary for the infant to have the disorder.
A case report of a 63-year-old woman who was diagnosed with hyperekplexia highlights that diagnosis can occur at any age. It's crucial to raise awareness about this condition to ensure early and accurate diagnosis, leading to appropriate treatment and management.
References: [1] Clinical description of hyperekplexia featuring startle-triggered stiffening beyond infancy and the response to clonazepam treatment [3] Natural history and management of hyperekplexia [5] Comprehensive review on hyperekplexia
- Beyond infancy, public awareness and early diagnosis of hyperekplexia are crucial to ensure appropriate treatment and management of the condition, as misdiagnosis can initially misidentify it as epilepsy.
- Hyperekplexia, a genetic neurology disorder characterized by exaggerated startle responses and motor difficulties, can present challenges beyond the first year of life, necessitating other genetic testing to identify specific gene mutations responsible.
- Proper treatment for hyperekplexia beyond infancy often involves pharmacological therapy, such as clonazepam, which enhances GABA_A receptor activity to reduce neuronal hyperexcitability, but physical safety precautions and avoidance of known startle triggers are also vital.
- In adulthood, hyperekplexia can affect gait and breathing, necessitating physical and cognitive therapy to lessen fear of falling and improve walking, as well as management strategies for episodes that may diminish but remain disabling if left untreated.
- Health-and-wellness professionals in various medical-conditions fields, including pediatrics, neurology, mental health, and neurological disorders, may collaborate in rare or severe forms of hyperekplexia to offer multidisciplinary care and ensure optimal patient outcomes.
- The inheritance pattern of hyperekplexia can be autosomal dominant or autosomal recessive, meaning that either one gene copy from one parent or both gene copies from both parents carrying a mutation can result in the disorder, demonstrating the complexity of this condition in the science of genetics.
