Abstracts

Rationale: Pediatric epilepsy can be caused by various conditions, including specific syndromes. It is noteworthy to know the specific genetic causes in epilepsy for the understanding of the pathogenesis as well as management for the better outcome. Whole exome sequencing may reveal the genetic cause in epilepsy syndrome especially accompanying severe cognitive impairment eventhough there is no abnormal findings by conventional chromosomal studies.Methods: We performed whole exome sequencing for searching genetic causes of specific cases.Results: Case 1 : A 9-year-and-11-month-old girl was brought to the Dankook University Hospital due to intractable seizure occurring daily more than 1 episode which developed 2 years ago. She had dysmorphic faces such as deep bush eyebrows, anteverted nares, micrognathia, and low posterior hairlines. She was born with gestational age 36+5weeks, and birth weight 1900g. She was short and had severe intellectual disabilities. Her mother and her elderly sister also had cognitive impairment, although her mother can take care of herself. EEG showed intermittent spike discharges from the right frontotemporal areas. Brain MRI revealed fimbria atrophy of left hippocampus. Conventional and microarray chromosomal study did not reveal any specific abnormalities. Therefore whole exome sequencing was performed in 4 family members which showed nonsense mutation of the gene HDAC8 in patient, sister and her mother, confirming a familial X-linked Cornelia de Lange syndrome caused by HDAC8 nonsense mutation. Case 2 : A 6 month-old-female patient without any specific familial history visited Dankook University Hospital due to developmental delay. She was born on 37 weeks of gestational age, and her weight was 2.6 kg. She did not reveal any notable abnormality at birth. On her age of 1 year and 5 months, seizures developed 3~4 times every week and EEG showed frontal spike wave discharges. After anticonvulsant medication, there was decline in frequency of seizure attack, and completely controlled at 5 years of age. Brain MRI and chromosomal study showed negative findings. Her hand radiograph showed brachydactly type E. Metabolic screening for inborn errors of amino acids, lipids, and organic acids metabolism turned out negative. By whole exome sequencing, de novo terminal deletion of 2q37 including gene HDAC4 was identified. Now she is 21 years old. She has profound mental retardation. Her intelligence quality, measured by KWAIS based on her performance, marked 24. Her social ability is retarded and is incapable of naming herself. She commands only a single word or meaningless onomatopoeia for communication. She compulsively washes her hand and is obsessed with her belongings such as her blanket as her autistic feature.Conclusions: Here we report two rare cases with severe intellectual disability and epilepsy caused by de novo mutation of HDAC8 and de novo terminal deletion of 2q37 including HDAC4 confirmed by whole exome sequencing.