Abstracts

Rationale: Hereditary hyperekplexia is a rare neurological disorder characterized by exaggerated motor startle responses. It can be caused by mutations of the glycine receptor alpha 1 (GLRA1) gene located on chromosome 5. Clonazepam is typically the first line therapy. This disorder can be misdiagnosed as generalized seizures. We report a case of a 9-year-old boy with clinical diagnosis of hereditary hyperekplexia confirmed with positive mutation and overlapping generalized epilepsy who responded well to levetiracetam. Methods: This is a case report of a child with hyperekplexia who subsequently developed epilepsy. Results: This is a 9-year-old Hispanic boy who was delivered vaginally at full term with no perinatal complications. Prenatally, mother had reported increase in-utero fetal movements. Soon after birth, he was noticed to have exaggerated motor startle reflex in response to a stimuli, and was diagnosed with hyperekplexia. He was initially treated with clonazepam with minimal improvement and by 4 years of age it was discontinued. At 6 years old he also started having convulsions, described as generalized tonic-clonic activity associated with eyes deviation upwards, facial cyanosis and unresponsiveness, typically lasting less then 5 minutes. These events were followed by postictal confusion and had no known triggers. He was started on levetiracetam, which successfully treated both his previously uncontrolled startle reflexes and his new onset seizures. Developmentally, he has speech delay and is in special education classes. Physical exam is remarkable for startle when his nose is tapped. Work-up included the hyperekplexia panel with sequencing of the GLRA1 gene; this revealed two heterozygous variants, one in exon 9, leading to the substitution of histidine for arginine at amino acid 428 previously described and the second, in exon 7, with substitution of leucine for phenylalanine in amino acid 235 which is a novel variant not previously described. An awake only electroencephalogram was obtained during which the non-epileptic nature of these motor startles was captured. No generalized tonic- clonic activity was captured. Interictal EEG was normal. Brain MRI was normal. Conclusions: Hereditary hyperekplexia is a rare disorder that is often mistaken for generalized epilepsy. It is important to recognize that both entities may coexist, as is the case of this patient. Initial treatment with clonazepam did not show significant improvement in his exaggerated startle reflex. However, later treatment with levetiracetam for treatment of epilepsy was also, interestingly, beneficial for treatment of his motor startle reflex. Patients with hyperekplexia who are poorly responsive to benzodiazepines may benefit from treatment with levetiracetam. This is the first pediatric case reported of hereditary hyperekplexia with overlapping generalized epilepsy responsive to levetiracetam in the literature; one other pediatric case has been reported of neonatal sporadic hyperekplexia with negative mutation responsive to levetiracetam, however, in that case no generalized seizures were reported.