颅骨-豆状肌-缝合发育不良(CLSD,OMIM#607812)是一种罕见的遗传病,其特征是晚关闭的fontanels,骨骼缺损,畸形,和由SEC23A基因的双等位基因或单等位基因变异引起的先天性白内障。常染色体隐性遗传(AR-CLSD)在SEC23A中具有纯合或复合杂合变体的几种情况下得到了广泛的证明。而常染色体显性遗传(AD-CLSD)涉及杂合遗传变异仅在3例患者中报道。SEC23A基因编码称为外壳蛋白复合物II(COPII)的蛋白质外壳复合物的主要成分之一,负责从内质网(ER)向高尔基复合体(GC)输出的囊泡包膜的生成。AR-CLSD和AD-CLSD表现出共同的特征,尽管每种形式也呈现出独特和独特的特征。在这里,我们描述了一个罕见的病例,一个10岁的男孩,有一个前font骨的历史,只在9岁时关闭。病人的身材比例很短,低重量,和神经损伤,包括智力残疾,全球发育迟缓,协调异常,肌张力障碍,和电机的振动,连同畸形,比如宽的前fonal,超端粒,额前带,宽阔的鼻子,高拱形腭,和小颌畸形。进行了三联临床外显子组,和SEC23A中的从头杂合错义变体(p。Arg716Cys)被鉴定。这是由SEC23A中的从头杂合错义变体引起的CLSD的第一例报道,表现出以前从未描述过的特定神经系统表现。第一次,我们使用患者和文献中记录最多的8例病例的数据进行了全面的表型-基因型相关性研究.我们的工作使我们能够识别两种形式的CLSD(AR-CLSD,ADCLSD),提供有价值的见解,可以指导医生在诊断过程中。值得注意的是,神经特征的详细描述,如智力障碍,全球发育迟缓,和运动障碍之前没有记录。此外,由于缺乏对这些患者的临床诊断和适当随访的指南,我们的文献综述在CLSD的当前格局中至关重要。尤其是在童年。
Cranio-lenticulo-sutural dysplasia (CLSD, OMIM #607812) is a rare genetic condition characterized by late-closing fontanels, skeletal defects, dysmorphisms, and congenital cataracts that are caused by bi-allelic or monoallelic variants in the SEC23A gene. Autosomal recessive inheritance (AR-CLSD) has been extensively documented in several cases with homozygous or compound heterozygous variants in SEC23A, whereas autosomal dominant inheritance (AD-CLSD) involving heterozygous inherited variants has been reported just in three patients. The SEC23A gene encodes for one of the main components of a protein coat complex known as coat-protein-complex II (COPII), responsible for the generation of the envelope of the vesicles exported from the endoplasmic reticulum (ER) toward the Golgi complex (GC). AR-CLSD and AD-CLSD exhibit common features, although each form also presents distinctive and peculiar characteristics. Herein, we describe a rare case of a 10-year-old boy with a history of an anterior fontanel that closed only at the age of 9. The patient presents with short proportionate stature, low weight, and neurological impairment, including intellectual disability, global developmental delay, abnormal coordination, dystonia, and motor tics, along with dysmorphisms such as a wide anterior fontanel, hypertelorism, frontal bossing, broad nose, high-arched palate, and micrognathia. Trio clinical exome was performed, and a de novo heterozygous missense variant in SEC23A (p.Arg716Cys) was identified. This is the first reported case of CLSD caused by a de novo heterozygous missense variant in SEC23A presenting specific neurological manifestations never described before. For the first time, we have conducted a comprehensive phenotype-genotype correlation using data from our patient and the eight most well-documented cases in the literature. Our work has allowed us to identify the main specific and characteristic signs of both forms of CLSD (AR-CLSD, AD CLSD), offering valuable insights that can guide physicians in the diagnostic process. Notably, detailed descriptions of neurological features such as intellectual disability, global developmental delay, and motor impairment have not been documented before. Furthermore, our literature overview is crucial in the current landscape of CLSD due to the absence of guidelines for the clinical diagnosis and proper follow-up of these patients, especially during childhood.