Stiff Baby Syndrome (SBS), also known as Neonatal Hyperekplexia or Startle Disease, is a rare neurological disorder characterized by pervasive muscle rigidity and episodes of muscle spasms immediately after birth. The disorder results from a disruption in the nervous system’s ability to regulate muscle activity, preventing infants from properly relaxing their muscles. This stiffness can lead to life-threatening complications, such as sudden respiratory compromise. Prompt medical evaluation and diagnosis are necessary to begin management and improve the infant’s long-term outcome.
Defining Stiff Baby Syndrome
Stiff Baby Syndrome is a rare inherited neurological condition presenting with a triad of symptoms: generalized hypertonia, an exaggerated startle reflex, and stiffness that temporarily ceases during sleep. It is often called Hyperekplexia, which describes the condition’s primary feature, the excessive startle response. The disorder is rare, with fewer than 200 cases identified worldwide, though its true prevalence may be higher due to misdiagnosis.
The physiological mechanism involves a failure of inhibitory signaling within the central nervous system, particularly in the brainstem and spinal cord. Inhibitory neurotransmitters like glycine normally quiet nerve cells, preventing continuous muscle contraction. In SBS, this inhibitory pathway is faulty, leading to neuronal hyperexcitability and continuous, unregulated muscle activity. This lack of proper “braking” results in the persistent stiffness and the exaggerated reaction to stimuli that define the syndrome.
Identifying the Underlying Causes
The primary cause of Stiff Baby Syndrome is genetic mutations that impair the function of the inhibitory glycine neurotransmitter system. Most cases are linked to mutations in the GLRA1 gene, which provides instructions for making the alpha-1 subunit of the glycine receptor protein. If this subunit is defective, the receptor cannot effectively bind to glycine, failing to stop the signal that causes muscles to contract.
Mutations in other genes, such as GLRB (coding for the beta subunit) and SLC6A5 (coding for the glycine transporter GlyT2), can also cause the disorder. These defects are typically inherited, often following an autosomal dominant or recessive pattern, though some cases arise from de novo mutations. The genetic error prevents the nerve cell’s chlorine ion channels from opening correctly, which is necessary for neuronal inhibition.
This lack of inhibitory signaling drives the syndrome’s pathology. While most cases are hereditary (primary hyperekplexia), acquired causes, such as certain autoimmune disorders or brainstem injuries, can rarely occur, though they are uncommon in neonates. The genetic basis classifies the condition as a channelopathy, explaining the disruption in neurological control over muscle tone.
Recognizable Signs and Physical Manifestations
The most pervasive sign of Stiff Baby Syndrome is generalized muscle stiffness, or hypertonia, typically noticeable immediately after birth. This rigidity is constant when the infant is awake, making it difficult for caregivers to change or hold the baby comfortably. A key diagnostic feature is that this stiffness noticeably decreases or disappears entirely when the infant is asleep.
A hallmark feature is the exaggerated startle reflex (hyperekplexia), triggered by sudden stimuli like a loud noise, bright light, or light touch. The excessive startle response leads to a brief, severe episode of generalized rigidity where the infant becomes stiff and immobile. During these episodes, infants may experience interrupted breathing (apnea), which carries a risk of cyanosis and can be life-threatening.
The persistent hypertonia also impacts feeding, as stiffness in the jaw and throat muscles makes sucking and swallowing difficult. Newborns often display a high-pitched or “staccato” cry due to rigidity affecting the vocal cords and chest muscles. Other manifestations include hypokinesia (a reduction in spontaneous movement) and nocturnal myoclonic jerks (sudden muscle twitches occurring as the infant falls asleep).
Diagnosis and Therapeutic Approaches
Diagnosis
Diagnosis is often initiated through a clinical evaluation, where a physician recognizes the characteristic triad of generalized hypertonia, the exaggerated startle reflex, and immediate post-startle rigidity. Tapping the infant’s nose can elicit generalized stiffness in a non-habituating way, a clinical sign highly suggestive of the condition. It is important to distinguish SBS from other conditions, such as epilepsy, which may present with similar rigidity or jerking movements.
To confirm the diagnosis, physicians rely on electrophysiological studies and genetic testing. An electromyography (EMG) can reveal continuous motor unit activity in affected muscles, even at rest, demonstrating nervous system hyperexcitability. Genetic testing identifies mutations in genes such as GLRA1, providing a definitive diagnosis.
Therapeutic Approaches
The primary management involves pharmacological interventions aimed at restoring inhibitory signaling in the central nervous system. Benzodiazepines, such as Clonazepam, are the treatment of choice because they enhance the effects of the inhibitory neurotransmitter GABA, compensating for the defective glycine pathway. These medications reduce the frequency and severity of the exaggerated startle responses and generalized muscle stiffness.
Clonazepam dosing is highly individualized based on the infant’s weight and clinical response, starting low and gradually increasing as needed. Supportive care is a major component of treatment, including close monitoring to mitigate the risk of apnea and sudden infant death. Physical therapy is often incorporated to manage hypertonia, improve motor development, and maintain muscle flexibility.