Chen Yuxi, Liu Hongyuan, Zhou Jingwei, Yang Xi, Jia Hechen, Ma Gang, Sun Bin, Chen Hongrui, Jin Yunbo, Hua Chen, Lin Xiaoxi
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Int J Dermatol. 2025 Apr;64(4):693-701. doi: 10.1111/ijd.17504. Epub 2024 Oct 4.
Capillary malformation-arteriovenous malformation (CM-AVM) is a rare genetic disorder characterized by multiple small capillary malformations (CMs) and arteriovenous malformations (AVMs), which has been linked with pathogenic variants in RASA1 and EPHB4. However, more data are needed to explore the phenotypic characteristics and the association between genotypes and clinical phenotypes.
Our aim was to investigate the phenotypic and genetic characteristics of CM-AVM in East Asians, identify potential unique phenotypes, and conduct genotype-phenotype association analyses.
This is a single-center study prospectively collecting CM-AVM patients' clinical data, with genetic data from blood or tissue samples.
A total of 59 patients were enrolled. Thirty-two individuals had a leading CM greater than Schobinger stage II. The trigeminal nerve branches and greater auricular, transverse cervical, and lesser occipital nerves' somatosensory innervation zones divided head and neck CMs into six zones: V1, V2, V3, GA, TC, and LO zones. GA, TC, and LO zones had a positive correlation with one another but a negative correlation with V2 zone involvement. The RASA1 and EPHB4 pathogenic variants were detected in 41 out of 59, which showed two types of variant allele frequency (VAF) distributions. VAF above 30% made RASA1 pathogenic variants more susceptible to multifocal CMs than those below 30%.
Leading CMs in the head and neck exhibit two segmentation patterns, anterior and lateral, which may differ in ear involvement and progression. Germline RASA1 pathogenic variants increased multifocal CM risk more than the somatic variants.
毛细血管畸形 - 动静脉畸形（CM - AVM）是一种罕见的遗传性疾病，其特征为多发小毛细血管畸形（CMs）和动静脉畸形（AVMs），与RASA1和EPHB4的致病变异有关。然而，需要更多数据来探索其表型特征以及基因型与临床表型之间的关联。
我们的目的是研究东亚人群中CM - AVM的表型和遗传特征，识别潜在的独特表型，并进行基因型 - 表型关联分析。
这是一项单中心研究，前瞻性收集CM - AVM患者的临床数据，并从血液或组织样本中获取遗传数据。
共纳入59例患者。32例患者的主要CM大于Schobinger II期。三叉神经分支以及耳大神经、颈横神经和枕小神经的躯体感觉神经支配区域将头颈部CMs分为六个区域：V1、V2、V3、GA、TC和LO区。GA、TC和LO区彼此呈正相关，但与V2区受累呈负相关。59例患者中有41例检测到RASA1和EPHB4致病变异，显示出两种变异等位基因频率（VAF）分布类型。VAF高于30%时，RASA1致病变异比低于30%时更易发生多灶性CMs。
头颈部主要CMs表现出两种分割模式，即前部和外侧部，在耳部受累和进展方面可能有所不同。种系RASA1致病变异比体细胞变异增加多灶性CM风险的程度更大。
