Hyperekplexia, also known as stiff baby syndrome, is a rare neurological disorder characterized by abnormal startle responses and muscle stiffness. The condition primarily affects neonates and infants, though milder forms can persist into adulthood.

Clinical Features:

1. Neonatal Stiffness:

   • Generalized muscle rigidity, which can mimic increased tone, is often present at birth.

2. Excessive Startle Reflex:

   • Exaggerated startle responses to tactile, auditory, or visual stimuli are hallmark features.
   • Startle can trigger stiffening of the entire body (generalized tonic reflex), leading to falls or apnea.

3. Prolonged Apnea:

   • Severe startle episodes may cause apnea and cyanosis, which can be life-threatening.

Genetics:

1. Mutations in GLRA1:

   • Hyperekplexia is commonly caused by mutations in the GLRA1 gene, located on chromosome 5q31.2.
   • This gene encodes the α1-subunit of the glycine receptor, a major inhibitory neurotransmitter receptor in the central nervous system.

2. Inheritance:

   • Most cases follow an autosomal dominant inheritance pattern, although autosomal recessive cases have been reported.

3. Other Gene Mutations:

   • Less frequently, mutations in other genes related to glycinergic transmission (e.g., GLRB, SLC6A5) may also cause hyperekplexia.

Diagnosis:

1. Clinical Presentation:

   • Neonates presenting with marked stiffness and exaggerated startle response are often diagnosed based on clinical observation.

2. Genetic Testing:

   • Identification of mutations in GLRA1 or related genes confirms the diagnosis.

3. Electrophysiological Studies:

   • EMG during startle episodes may demonstrate a distinct pattern of continuous motor unit activity.

Treatment:

1. Clonazepam:

   • The drug of choice, as it enhances inhibitory GABAergic transmission and reduces symptoms.

2. Supportive Care:

   • Neonatal monitoring to prevent complications such as apnea.
   • Safety precautions to avoid injury from startle-induced falls.

3. Prognosis:

   • Early diagnosis and treatment improve outcomes significantly.
   • In some cases, symptoms decrease in severity with age, though the startle reflex may persist.