Yang Ying, Chen Liqing, Wang Zhenzhen, Ding Yaling, Liu Yan
Department of Pediatrics, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mol Genet Genomic Med. 2025 Jan;13(1):e70058. doi: 10.1002/mgg3.70058.
Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder. Although individuals with variants in the SMC1A gene are less commonly seen in CdLS, they exhibit a high incidence of epilepsy and atypical phenotypic variability.
The clinical data of a patient with non-classic CdLS and epilepsy caused by an SMC1A variant were summarized. A literature review was conducted to analyze the genotype-phenotype correlations and epilepsy characteristics in related cases.
A 5-year-6-month-old female patient presented with facial features, double outlet right ventricle (DORV), and recurrent epilepsy. Whole exome sequencing (WES) identified a de novo heterozygous frameshift mutation, c.2890_2893del (p.Ser964Valfs*26), in the SMC1A gene. A review of the literature identified several characteristics of non-classic CdLS with epilepsy caused by SMC1A variants: the majority of cases were non-classic (81.5%), predominantly female (68.2%), with a median onset age of 11.5 months. Common features included severe/profound developmental delay (52.6%), hypotonia (18.2%), cardiovascular anomalies (36.4%), and intrauterine growth retardation (IUGR) (22.7%). Among the non-classic cases, seizure clusters occurred in 22.7%, status epilepticus in 18.2%, and drug-resistant epilepsy in 33.3%. Genotypes in non-classic cases included missense mutations (40.9%), frameshift mutations (31.8%), splice site variants (9.1%), nonsense mutations (9.1%), deletions (4.5%), and truncations (4.5%).
Our study expanded the phenotypic data and mutational spectrum of non-classic CdLS with epilepsy caused by SMC1A variants. Compared to individuals with the classic form of CdLS, the non-classic cases appeared more frequently in females and were associated with a higher prevalence of severe/profound developmental delay and cardiovascular anomalies. In contrast, IUGR was significantly less common in non-classic individuals. Regarding epilepsy characteristics, some individuals including seizure clusters, status epilepticus, drug resistance, and hypotonia, no significant differences were observed between classic and non-classic cases. The predominant genotypes in non-classic cases were missense and frameshift mutations.
科妮莉亚·德朗热综合征（CdLS）是一种多系统遗传性疾病。虽然SMC1A基因变异的个体在CdLS中较少见，但他们癫痫发病率高且具有非典型的表型变异性。
总结了1例由SMC1A变异导致的非典型CdLS合并癫痫患者的临床资料。进行文献综述以分析相关病例的基因型-表型相关性及癫痫特征。
一名5岁6个月大的女性患者出现面部特征、右心室双出口（DORV）及反复癫痫发作。全外显子组测序（WES）在SMC1A基因中鉴定出一个新生杂合移码突变，c.2890_2893del（p.Ser964Valfs*26）。文献综述确定了由SMC1A变异导致的非典型CdLS合并癫痫的几个特征：大多数病例为非典型（81.5%），以女性为主（68.2%），中位发病年龄为11.5个月。常见特征包括重度/极重度发育迟缓（52.6%）、肌张力低下（18.2%）、心血管异常（36.4%）及宫内生长迟缓（IUGR）（22.7%）。在非典型病例中，癫痫发作丛集占22.7% ,癫痫持续状态占18.2%，耐药性癫痫占33.3%。非典型病例的基因型包括错义突变（40.9%）、移码突变（31.8%）、剪接位点变异（9.1%）、无义突变（9.1%）、缺失（4.5%）及截短（4.5%）。
我们的研究扩展了由SMC1A变异导致的非典型CdLS合并癫痫的表型数据和突变谱。与典型形式的CdLS个体相比，非典型病例在女性中更常见，且与重度/极重度发育迟缓和心血管异常的较高患病率相关。相比之下，IUGR在非典型个体中明显较少见。关于癫痫特征，包括癫痫发作丛集、癫痫持续状态、耐药性和肌张力低下在内的一些个体，典型和非典型病例之间未观察到显著差异。非典型病例中主要的基因型是错义突变和移码突变。
