1例遗传性血管病、肾病、动脉瘤和肌肉痉挛综合征幼儿的临床特征及COL4A1基因型研究

Clinical features and COL4A1 genotype of a toddler with hereditary angiopathy with nephropathy, aneurysms and muscle cramps syndrome

摘要:

遗传性血管病、肾病、动脉瘤和肌肉痉挛（HANAC）综合征是由COL4A1基因变异导致的常染色体显性遗传病，主要表现为脑白质病变、动脉瘤、视网膜动脉迂曲、多囊肾、镜下血尿、肌肉痉挛等。该文报道1例COL4A1基因变异导致HANAC综合征的临床特征及基因型特点。患儿男，1岁8个月，幼儿期隐匿起病，主要表现为发热抽搐、侧脑室旁及双侧半卵圆中心脑白质病变、左侧基底节旁软化灶、视网膜动脉硬化、镜下血尿、肌肉痉挛。全外显子组测序结果证实患儿COL4A1基因存在（NM_001845）c.4150+1（IVS46）G > T致病性杂合新发变异，从而确诊为HANAC综合征。针对不明原因脑白质病变、卒中、血尿、多囊肾、白内障、视网膜动脉迂曲等病变的患儿或有相关家族史的家系，建议完善COL4A1基因检测。

Abstract:

Hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome is an autosomal dominant genetic disease caused by COL4A1 gene mutation, with major clinical manifestations of white matter lesion, aneurysm, retinal artery tortuosity, polycystic kidney, microscopic hematuria and muscle cramps. This article reports the clinical features and genotype of one toddler with HANAC syndrome caused by COL4A1 gene mutation. The boy, aged 1 year and 8 months, had an insidious onset, with the clinical manifestations of pyrexia and convulsion, white matter lesions in the periventricular region and the centrum semiovale on both sides, softening lesions beside the left basal ganglia, retinal arteriosclerosis, microscopic hematuria and muscle cramps. Whole exome sequencing revealed a pathogenic de novo heterozygous mutation in the COL4A1 gene, (NM_001845) c.4150+1(IVS46)G > T, and therefore, the boy was diagnosed with HANAC syndrome. COL4A1 gene mutation detection should be performed for children with unexplained white matter lesion, stroke, hematuria, polycystic kidney, cataract and retinal artery tortuosity or families with related history.