Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.
Mol Psychiatry. 2019 Feb;24(2):241-251. doi: 10.1038/s41380-018-0066-9. Epub 2018 Jun 11.
Epilepsy and Mental Retardation Limited to Females (EFMR) is an infantile onset disorder characterized by clusters of seizures. EFMR is due to mutations in the X-chromosome gene PCDH19, and is underpinned by cellular mosaicism due to X-chromosome inactivation in females or somatic mutation in males. This review characterizes the neuropsychiatric profile of this disorder and examines the association of clinical and molecular factors with neuropsychiatric outcomes. Data were extracted from 38 peer-reviewed original articles including 271 individual cases. We found that seizure onset ≤12 months was significantly associated (p = 4.127 × 10) with more severe intellectual disability, compared with onset >12 months. We identified two recurrent variants p.Asn340Ser and p.Tyr366Leufs*10 occurring in 25 (20 unrelated) and 30 (11 unrelated) cases, respectively. PCDH19 mutations were associated with psychiatric comorbidities in approximately 60% of females, 80% of affected mosaic males, and reported in nine hemizygous males. Hyperactive, autistic, and obsessive-compulsive features were most frequently reported. There were no genotype-phenotype associations in the individuals with recurrent variants or the group overall. Age at seizure onset can be used to provide more informative prognostic counseling.
女性特发性癫痫伴智力低下（EFMR）是一种以癫痫发作簇为特征的婴儿期起病的疾病。EFMR 是由于 X 染色体基因 PCDH19 的突变引起的，其基础是由于女性 X 染色体失活或男性体细胞突变导致的细胞嵌合体。本综述描述了该疾病的神经精神特征，并研究了临床和分子因素与神经精神结局的关联。数据来自 38 篇同行评议的原始文章，包括 271 个个体病例。我们发现，与发病>12 个月的患者相比，发病≤12 个月的患者（p = 4.127 × 10）与更严重的智力残疾显著相关。我们发现了两种复发性变异体 p.Asn340Ser 和 p.Tyr366Leufs*10，分别发生在 25 例（20 例无关联）和 30 例（11 例无关联）患者中。大约 60%的女性、80%的受影响嵌合男性存在 PCDH19 突变，并在 9 例半合子男性中报道。多动、自闭症和强迫症特征最为常见。在具有复发性变异体的个体或总体组中，没有基因型-表型相关性。发病年龄可用于提供更具信息性的预后咨询。
