Barañano Kristin W, Kimball Amy, Fong Susan L, Egense Alena S, Hudon Catherine, Kline Antonie D
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Harvey Institute for Human Genetics, Greater Baltimore Medical Center, Baltimore, MD, USA.
J Child Neurol. 2022 Apr;37(5):390-396. doi: 10.1177/08830738221081244. Epub 2022 Mar 3.
Cornelia de Lange syndrome is a rare developmental malformation syndrome characterized by small stature, limb anomalies, distinctive facial features, developmental delays, and behavioral issues. The diagnosis of Cornelia de Lange syndrome is made clinically or on the basis of an identified variant in one of the genes associated with Cornelia de Lange syndrome. variants are the cause of 5% of the cases of Cornelia de Lange syndrome. is located on the X-chromosome and is thought to escape X-inactivation in some females. Patients with variants are being increasingly identified through panel testing or exome sequencing without prior clinical suspicion of Cornelia de Lange syndrome. In general, intractable epilepsy is not considered a prominent feature of Cornelia de Lange syndrome, yet this is found in these patients with variants. Here we report on a series of patients with variants and intractable epilepsy. In contrast to patients with typical -associated Cornelia de Lange syndrome, all of the identified patients were female, and when available, X-inactivation studies were highly skewed with truncating variants. We describe the medical involvement and physical appearance of the participants, compared to the diagnostic criteria used for classical Cornelia de Lange syndrome. We also report on the clinical characteristics of the epilepsy, including age of onset, types of seizures, electroencephalographic (EEG) findings, and response to various antiepileptic medications. These findings allow us to draw conclusions about how this population of patients with variants fit into the spectrum of Cornelia de Lange syndrome and the broader spectrum of cohesinopathies and allow generalizations that may impact clinical care and, in particular, epilepsy management.
科妮莉亚·德朗热综合征是一种罕见的发育畸形综合征，其特征为身材矮小、肢体异常、独特的面部特征、发育迟缓及行为问题。科妮莉亚·德朗热综合征的诊断基于临床症状或与该综合征相关的某个基因中已鉴定出的变异。这些变异导致了5%的科妮莉亚·德朗热综合征病例。该基因位于X染色体上，被认为在一些女性中逃避了X染色体失活。通过基因检测板或外显子测序越来越多地鉴定出携带该变异的患者，而此前他们并无科妮莉亚·德朗热综合征的临床疑似症状。一般来说，难治性癫痫不被认为是科妮莉亚·德朗热综合征的突出特征，但在这些携带该变异的患者中却发现了这种情况。在此，我们报告一系列携带该变异且患有难治性癫痫的患者。与典型的与该基因相关的科妮莉亚·德朗热综合征患者不同，所有已鉴定出的患者均为女性，并且在可行的情况下，X染色体失活研究显示截短变异导致高度偏态。我们描述了参与者的医疗情况和外貌特征，并与经典科妮莉亚·德朗热综合征的诊断标准进行了比较。我们还报告了癫痫的临床特征，包括发病年龄、癫痫发作类型、脑电图（EEG）结果以及对各种抗癫痫药物的反应。这些发现使我们能够得出关于这群携带该变异的患者如何符合科妮莉亚·德朗热综合征谱系以及更广泛的黏连蛋白病谱系的结论，并得出可能影响临床护理，特别是癫痫管理的一般性结论。
