Congenital Hyperekplexia: A Visual Diagnosis

Background/Purpose: Hereditary hyperekplexia, also named stiff baby syndrome or familial startle disease, is a rare disorder hampering glycinergic neurotransmission, especially at the level of the brain stem. GLRA1 mutations are most frequent, but genetic defects in other components of the glycinergic synapse may also be causative. While hypertonia, typically responding well to treatment with smaller doses of benzodiazepines, usually resolves after infancy, an exaggerated startle reflex triggered by acoustic and tactile stimuli becomes more prominent and persists the entire life.

Methods: Clinical examination and genetic testing by Sanger sequencing were conducted in the index patient.

Results: A 3-month-old Turkish baby was referred because of suspected tonic seizures. Clinical examination revealed marked hypertonia. Episodes of generalized stiffness could be provoked by noise; and tapping on the boy’s nose resulted in a characteristic reaction of facial twitching accompanied by head extension, and a generalized flexor spasm, not habituating when repeated. Genetic testing revealed a homozygous mutation in the GLRA1 gene, encoding for the α-subunit of the postsynaptic inhibitory glycine receptor, which has been previously reported in Turkish hyperekplexia families.

Conclusion: Making the diagnosis is important for avoiding unnecessary examinations, and sometimes for treatment, as prolonged episodes of stiffening in severely affected babies may cause laryngospasms with apnea and even death.