Intellectual disability syndrome (IDS) associated with a hereditary persistence of fetal haemoglobin (HbF), also known as Dias-Logan syndrome, is commonly characterised by psychomotor developmental delay, intelectual disability, language delay, strabismus, thin upper lip, abnormalities of external ears, microcephaly, downslanting palpebral fissures. Sporadically, autism spectrum disorders and blue sclerae in infancy have been reported in IDS. Rarely, IDS-affected patients present with epilepsy and/or epileptic syndromes. It has been shown that a haploinsufficiency of the B cell leukaemia/lymphoma 11A gene (BCL11A) is responsible for IDS. Herein, we identified a novel de novo frameshift deletion (c.271delG; p.E91Afs*2) in the BCL11A gene in a boy affected with IDS. Interestingly, this heterozygous loss-of-function BCL11A mutation was also associated with a generalised idiopathic epilepsy and severe language delay observed in the patient. Moreover, our study showed that the combination of molecular genetic analyses with the monitoring of HbF was essential to make the final diagnosis of Dias-Logan syndrome. Because our patient suffered from well-controlled epilepsy, we propose to include the BCL11A gene in routinely used molecular genetic epilepsy-related gene panels. Additionally, many of the clinical features of IDS overlap with symptoms observed in patients with suspected alcohol spectrum disorders. Therefore, we also suggest monitoring HbF levels in patients with these syndromes to further facilitate clinical diagnosis.
Mol Syndromol

中文翻译：

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智障综合征和癫痫患者BCL11A基因的新型从头突变。

与胎儿血红蛋白（HbF）的遗传性持续性相关的智力障碍综合症（IDS），也称为Dias-Logan综合征，通常表现为精神运动发育迟缓，智力障碍，语言迟缓，斜视，上唇细小，外耳异常，小头畸形，下睑裂。从零星的角度来看，IDS中已经报道了婴儿期的自闭症谱系障碍和蓝色巩膜。受IDS影响的患者很少出现癫痫和/或癫痫综合征。已经表明，B细胞白血病/淋巴瘤11A基因（BCL11A）的单倍剂量不足是造成IDS的原因。在本文中，我们鉴定了新的从头移码缺失（p.E91Afs * 2 c.271delG）BCL11A一个患有IDS的男孩的基因。有趣的是，这种杂合性功能丧失的BCL11A突变还与患者中发现的普遍性特发性癫痫和严重的语言延迟有关。此外，我们的研究表明，分子遗传学分析与HbF监测相结合对于最终诊断Dias-Logan综合征至关重要。由于我们的患者患有癫痫病的控制良好，因此我们建议纳入BCL11A常规使用的与分子遗传性癫痫相关的基因组中的基因。另外，IDS的许多临床特征与在可疑酒精谱系障碍患者中观察到的症状重叠。因此，我们还建议监测这些综合征患者的HbF水平，以进一步促进临床诊断。
摩尔综合症