Department of Medicine, Epilepsy Research Centre, The University of Melbourne, Austin Health, Melbourne, Victoria, Australia.
Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Epilepsia. 2019 Mar;60(3):429-440. doi: 10.1111/epi.14678. Epub 2019 Mar 3.
To investigate the occurrence of psychosis and serious behavioral problems in females with protocadherin 19 gene (PCDH19) pathogenic variants.
We evaluated whether psychosis and serious behavioral problems had occurred in 60 females (age 2-75 years) with PCDH19 pathogenic variants belonging to 35 families. Patients were identified from epilepsy genetics databases in Australia, New Zealand, the United States, and Canada. Neurologic and psychiatric disorders were diagnosed using standard methods.
Eight of 60 females (13%) from 7 families developed a psychotic disorder: schizophrenia (6), schizoaffective disorder (1), or an unspecified psychotic disorder (1). Median age at onset of psychotic symptoms was 21 years (range 11-28 years). In our cohort of 39 females aged 11 years or older, 8 (21%) developed a psychotic disorder. Seven had ongoing seizures at onset of psychosis, with 2 continuing to have seizures when psychosis recurred. Psychotic disorders occurred in the setting of mild (4), moderate (2), or severe (1) intellectual disability, or normal intellect (1). Preexisting behavioral problems occurred in 4 patients, and autism spectrum disorder in 3. Two additional females (3%) had psychotic features with other conditions: an adolescent had recurrent episodes of postictal psychosis, and a 75-year-old woman had major depression with psychotic features. A further 3 adolescents (5%) with moderate to severe intellectual disability had onset of severe behavioral disturbance, or significant worsening.
We identify that psychotic disorders, including schizophrenia, are a later-onset manifestation of PCDH19 Girls Clustering Epilepsy. Affected girls and women should be carefully monitored for later-onset psychiatric disorders.
探讨原钙黏蛋白 19 基因（PCDH19）致病性变异女性患者发生精神病和严重行为问题的情况。
我们评估了来自澳大利亚、新西兰、美国和加拿大的癫痫遗传学数据库中 35 个家系的 60 名（年龄 2-75 岁）PCDH19 致病性变异女性患者是否发生精神病和严重行为问题。使用标准方法诊断神经和精神障碍。
7 个家系的 8 名（13%）女性（6 名为精神分裂症，1 名为分裂情感性障碍，1 名为未特定的精神病性障碍）出现精神病。精神病症状的发病中位年龄为 21 岁（范围 11-28 岁）。在我们的 39 名年龄在 11 岁或以上的女性患者中，有 8 名（21%）患有精神病。精神病发作时，7 名患者持续有癫痫发作，2 名患者在精神病复发时仍有癫痫发作。精神病发生在 4 名患者存在轻度（4 例）、中度（2 例）或重度（1 例）智力障碍或智力正常（1 例）的情况下。4 名患者存在先前存在的行为问题，3 名患者存在自闭症谱系障碍。另外 2 名女性（3%）患有伴发其他疾病的精神病特征：1 名青少年反复发作癫痫后精神病，1 名 75 岁女性患有伴精神病特征的重度抑郁症。另外 3 名（5%）有中重度智力障碍的青少年出现严重行为障碍或显著恶化。
我们发现精神病，包括精神分裂症，是 PCDH19 相关性女孩癫痫聚类的迟发性表现。应仔细监测受影响的女孩和女性是否出现迟发性精神障碍。
