Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Division of Child Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Ann Neurol. 2020 Aug;88(2):396-406. doi: 10.1002/ana.25797. Epub 2020 Jun 29.
Rett syndrome, CDKL5-deficiency disorder, FOXG1 disorder, and MECP2 duplication disorder are developmental encephalopathies with shared and distinct features. Although they are historically linked, no direct comparison has been performed. The first head-to-head comparison of clinical features in these conditions is presented.
Comprehensive clinical information was collected from 793 individuals enrolled in the Rett and Rett-Related Disorders Natural History Study. Clinical features including clinical severity, regression, and seizures were cross-sectionally compared between diagnoses to test the hypothesis that these are 4 distinct disorders.
Distinct patterns of clinical severity, seizure onset age, and regression were present. Individuals with CDKL5-deficency disorder were the most severely affected and had the youngest age at seizure onset (2 months), whereas children with MECP2 duplication syndrome had the oldest median age at seizure onset (64 months) and lowest severity scores. Rett syndrome and FOGX1 were intermediate in both features. Smaller head circumference correlates with increased severity in all disorders and earlier age at seizure onset in MECP2 duplication syndrome. Developmental regression occurred in all Rett syndrome participants (median = 18 months) but only 23 to 34% of the other disorders. Seizure incidence prior to the baseline visit was highest for CDKL5 deficiency disorder (96.2%) and lowest for Rett syndrome (47.5%). Other clinical features including seizure types and frequency differed among groups.
Although these developmental encephalopathies share many clinical features, clear differences in severity, regression, and seizures warrant considering them as unique disorders. These results will aid in the development of disease-specific severity scales, precise therapeutics, and future clinical trials. ANN NEUROL 2020;88:396-406.
雷特综合征、CDKL5 缺乏症、FOXG1 综合征和 MECP2 重复综合征是具有共同和不同特征的发育性脑病。虽然它们在历史上有联系，但没有进行过直接比较。本文首次对头对头比较这些疾病的临床特征。
从雷特综合征和相关疾病自然史研究中招募的 793 名患者中收集了全面的临床信息。对这些诊断的临床严重程度、退化和癫痫发作进行了横断面比较，以检验这些疾病是 4 种不同疾病的假设。
存在不同模式的临床严重程度、癫痫发作年龄和退化。CDKL5 缺乏症患者的病情最严重，癫痫发作年龄最小（2 个月），而 MECP2 重复综合征患儿癫痫发作年龄中位数最大（64 个月），严重程度评分最低。雷特综合征和 FOGX1 则处于两者之间。所有疾病的头围越小与严重程度越高以及 MECP2 重复综合征的癫痫发作年龄越小呈正相关。发育性退化发生在所有雷特综合征患者中（中位数=18 个月），但只有 23%至 34%的其他疾病患者出现这种情况。在基线检查之前，CDKL5 缺乏症的癫痫发作发生率最高（96.2%），而雷特综合征的发生率最低（47.5%）。其他临床特征，包括癫痫发作类型和频率，在各组之间存在差异。
尽管这些发育性脑病有许多共同的临床特征，但严重程度、退化和癫痫发作的明显差异表明它们是不同的疾病。这些结果将有助于制定疾病特异性严重程度量表、精确治疗方法和未来临床试验。
