[Clinical and genetic analysis of hyperekplexia in a Chinese child and literature review].

To investigate the clinical and genetic features of a Chinese child with hyperekplexia and review the related literature. The clinical and genetic data of one patient with hyperekplexia, who had visited the department of Pediatrics, Peking University First Hospital in July 2012, were analyzed. "Hyperekplexia" "startle disease" "GLRB" were used as key words to search at CNKI, Wanfang and PubMed from the database from creation to August 2016. The one-year-old female patient showed exaggerated startle reflexes and generalized stiffness in response to external sudden, unexpected stimuli at 2 hours after birth, which existed every day. Her younger twin sister died of severe apnea due to a continuous generalized stiffness at the age of 7 months. Physical examination exhibited the positive nose-tapping reflex. There were no obvious abnormalities in laboratory tests, electroencephalogram (EEG) and neuroimaging tests. The patient was revealed to have compound heterozygous mutations in GLRB gene, c. 298-1G>A (or IVS4-1G>A) inherited from the father and c. 347T>C (p. L116P) inherited from the mother. The mutation L116P in GLRB gene was not reported before. During the follow-up until 5 years old, the girl's symptoms of startle reflexes and generalized stiffness were controlled with clonazepam treatment. Her mental development was normal, but she walked very carefully as wide-based gait to avoid of external sudden stimuli. Literature retrieval obtained 8 reports (all in English) with 39 GLRB-related cases. Combined analysis of the data of the 39 foreign cases and our case showed that the onset age of all 40 cases was in neonatal or and all presented exaggerated startle reflexes and generalized stiffness in response to external stimuli. Other symptoms included neonatal apneas (83%, 20/24), falls (56%, 15/27) and squint (42%, 10/24) etc. EEG (13/13) and brain imaging (90%, 28/31) were normal, or unrelated/nonspecific to hyperekplexia. In the total 17 mutations of GLRB gene found in 28 cases, the most frequent mutations were GLRB gene M177R (9 cases) and IVS5+ 5G>A (5 cases). Most cases (82%, 32/39) had received the treatment of clonazepam. The symptoms of hyperekplexia all could be improved in different degree after treatment, and 84% (32/38) of the cases were completely controlled or only existed exaggerated startle reflexes. The psychomotor development could be normal (13 cases) or retarded (25 cases). The patient presented typical clinical manifestations of hyperekplexia and had a good response to clonazepam. The patient carried GLRB gene mutations found by genetic analysis, and was finally diagnosed with hyperekplexia. The younger twin sister died due to lack of timely diagnosis and treatment, suggesting the significance of early detection and proper treatment for this disease.