目标:罗伯茨综合征(RBS),也被称为Roberts-SCphocomelia综合征,是由ESCO2基因突变引起的一种罕见的常染色体隐性遗传发育障碍。主要临床表现是产前和产后生长迟缓以及颅面和肢体畸形。这里,我们报道了中国青少年中的RBS,该青少年具有新的双等位基因ESCO2变异和复杂的脑血管疾病。
方法:病史,神经系统检查,神经影像学,在先证者和家庭中收集病理学。进行具有拷贝数变异分析的全外显子组测序(WES)以筛选遗传变异。
结果:先证者的临床特征是颅面和肢体畸形以及复杂的脑血管疾病。她在6岁时患有缺血性中风,并在13岁时死于动脉瘤继发的小脑出血。此外,神经影像显示了白质脑病的三联征,钙化,和囊肿。脑组织病理学检查显示血管瘤样改变和血管周围囊肿提示慢性小脑血管病变。全外显子组测序(WES)鉴定了ESCO2基因中的新型双等位基因变异(c.1220A>T,p.H407L和c.1562delC,p.A521fs)。
结论:我们描述了由新的ESCO2双等位基因变异引起的Roberts综合征的复杂脑血管疾病。该病例不仅扩大了Roberts综合征的大脑受累,而且扩大了白质脑病的神经影像学三联症的疾病谱,钙化,和囊肿。
Roberts syndrome (RBS), also known as Roberts-SC phocomelia syndrome, is a rare autosomal recessive developmental disorder caused by mutations in the ESCO2 gene. Cardinal clinical manifestations are pre- and postnatal growth retardation and craniofacial and limb malformations. Here, we report RBS in a Chinese adolescent with novel biallelic ESCO2 variations and complex cerebrovascular diseases.
Medical history, neurological examinations, neuroimaging, and pathology were collected in the proband and the family. Whole exome sequencing (WES) with copy number variation analysis was performed to screen for genetic variations.
The clinical features of the proband were craniofacial and limb malformations together with complex cerebrovascular diseases. She suffered ischemic stroke at 6 years old and died of cerebellar hemorrhage secondary to an aneurysm at 13 years old. Besides, neuroimaging showed the triad of leukoencephalopathy, calcifications, and cysts. Brain histopathology revealed angiomatous changes and perivascular cysts suggesting chronic small cerebral vasculopathy. Whole exome sequencing (WES) identified novel biallelic variations in the ESCO2 gene (c.1220A>T, p.H407L and c.1562delC, p.A521fs).
We describe complex cerebrovascular diseases in Roberts syndrome caused by novel ESCO2 biallelic variations. This case expands not only the cerebral involvement in Roberts syndrome but also the disease spectrum of the neuroimaging triad with leukoencephalopathy, calcifications, and cysts.