Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Pediatric Neurology, Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Epilepsia Open. 2023 Dec;8(4):1300-1313. doi: 10.1002/epi4.12799. Epub 2023 Aug 18.
The aim of this study was to describe the epilepsy phenotype in a large international cohort of patients with KBG syndrome and to study a possible genotype-phenotype correlation.
We collected data on patients with ANKRD11 variants by contacting University Medical Centers in the Netherlands, an international network of collaborating clinicians, and study groups who previously published about KBG syndrome. All patients with a likely pathogenic or pathogenic ANKRD11 variant were included in our patient cohort and categorized into an "epilepsy group" or "non-epilepsy group". Additionally, we included previously reported patients with (likely) pathogenic ANKRD11 variants and epilepsy from the literature.
We included 75 patients with KBG syndrome of whom 26 had epilepsy. Those with epilepsy more often had moderate to severe intellectual disability (42.3% vs 9.1%, RR 4.6 [95% CI 1.7-13.1]). Seizure onset in patients with KBG syndrome occurred at a median age of 4 years (range 12 months - 20 years), and the majority had generalized onset seizures (57.7%) with tonic-clonic seizures being most common (23.1%). The epilepsy type was mostly classified as generalized (42.9%) or combined generalized and focal (42.9%), not fulfilling the criteria of an electroclinical syndrome diagnosis. Half of the epilepsy patients (50.0%) were seizure free on anti-seizure medication (ASM) for at least 1 year at the time of last assessment, but 26.9% of patients had drug-resistant epilepsy (failure of ≥2 ASM). No genotype-phenotype correlation could be identified for the presence of epilepsy or epilepsy characteristics.
Epilepsy in KBG syndrome most often presents as a generalized or combined focal and generalized type. No distinctive epilepsy syndrome could be identified. Patients with KBG syndrome and epilepsy had a significantly poorer neurodevelopmental outcome compared with those without epilepsy. Clinicians should consider KBG syndrome as a causal etiology of epilepsy and be aware of the poorer neurodevelopmental outcome in individuals with epilepsy.
本研究旨在描述 KBG 综合征患者的癫痫表型，并研究可能的基因型-表型相关性。
我们通过联系荷兰的大学医疗中心、国际合作临床医生网络和先前发表过 KBG 综合征相关文章的研究小组，收集ANKRD11 变异患者的数据。所有携带可能致病性或致病性ANKRD11 变异的患者均被纳入我们的患者队列，并分为“癫痫组”或“非癫痫组”。此外，我们还纳入了文献中先前报道的携带（可能）致病性 ANKRD11 变异和癫痫的患者。
我们纳入了 75 名 KBG 综合征患者，其中 26 名患有癫痫。癫痫患者更常伴有中度至重度智力障碍（42.3%比 9.1%，RR 4.6 [95%CI 1.7-13.1]）。KBG 综合征患者的癫痫发作中位年龄为 4 岁（范围为 12 个月至 20 岁），大多数为全面性发作（57.7%），其中最常见的是强直-阵挛发作（23.1%）。癫痫类型主要分为全面性（42.9%）或全面性和局灶性合并（42.9%），不符合电临床综合征诊断标准。一半的癫痫患者（50.0%）在最后一次评估时至少有 1 年无抗癫痫药物（ASM）发作，但有 26.9%的患者患有药物难治性癫痫（ASM 失败≥2 种）。未发现癫痫或癫痫特征存在与基因型的相关性。
KBG 综合征中的癫痫多表现为全面性或全面性合并局灶性发作。未确定独特的癫痫综合征。与无癫痫的患者相比，患有 KBG 综合征和癫痫的患者神经发育结局明显较差。临床医生应将 KBG 综合征视为癫痫的病因，并意识到癫痫患者的神经发育结局较差。
