Abstracts

Rationale: Periventricular nodular heterotopia (PH) is a cerebral cortical migration abnormality characterized by heterotopic neurons that get trapped in the ventricular zone. Majority of PH is secondary to mutations in the Filamin A gene which is in the Xq28 region. Majority of female patients with PH have relatively normal cognition, but develop seizures in their teen ages. Some may have mild neurocognitive and psychiatric deficits. Males with Filamin A mutations die in utero, however, rare sporadic mosaic male cases have been noted. Methods: During a chart review of patients with PH, a 6 1/2-year-old girl with complex partial epilepsy, mild cognitive delay, learning disability, brittle teeth, a coin like skin lesion, and periventricular nodular heterotopia was identified. Results: The patient presented with nocturnal complex partial seizures at 5 year-10-months’ of age. EEG revealed sharply contoured slowing biposteriorly with left more than right occipital involvement consistent with cerebral cortical dysfunction in those areas. MRI of the brain revealed signal intensity consistent with gray matter signal outlining all margins of both atria, the temporal and occipital horns, and was consistent with periventricular heterotopia. She was initially treated with oxcarbazepine. The patient was born normally following an uneventful pregnancy. Her initial development was normal. After starting school however, a WISC IV assessment indicated a low average full scale IQ of 80 with statistically significant discrepancies among index and subset scores, revealing stronger working memory, but weaker verbal compression, perceptual reasoning, and processing speed. In WIAT II whereas her reading skills were strong, she had difficulty with writing and simple arithmetics. Family history was significant for learning disability, febrile seizures, and nonfebrile seizures. On exam the patient had brittle teeth with multiple cavities and fillings, a quarter dollar sized coin like hemangiomatoid skin-lesion. Her speech was fluent, however, she had difficulties in fulfilling complex commands in a timely fashion. She also had hard time performing simple arithmetics, and writing grammatically and syntactically correct sentences. The rest of her general and neurological examination was within normal limits for age. A Filamin A sequence analysis did not reveal mutations. A chromosomal microarray study, however, revealed a duplication in the chromosomal region 14q21.2-21.3. Conclusions: We present a syndrome of complex partial epilepsy, neurocognitive phenomena mainly manifesting as mild cognitive delay and learning disability, brittle teeth, coin-like skin lesion in the setting of PH. Lack of a mutation in the Filamin A gene and presence of a duplication in the chromosomal region 14q21.2-21.3 is intriguing. In order to better characterize this novel syndrome, and exclude the possibility of a familial variant, genetic testing of family members is being carried out.