关键词: 血管畸形, 色素性血管性斑痣性错构瘤病, 先天性毛细血管畸形, 异位蒙古斑, GNA11基因, GNAQ基因, 体细胞突变

Abstract: 【Abstract】 Objective To analyze the clinical characteristics and somatic mutation profiles of phakomatosis pigmentovascularis in children. Methods This study was a case series study. Clinical data were collected from 32 children with phakomatosis pigmentovascularis at the Department of Dermatology, Beijing Children′s Hospital, Capital Medical University. DNA was extracted from skin lesion tissues, and high-throughput whole-exome sequencing was performed to identify pathogenic gene mutations. Ultra-deep targeted sequencing was subsequently conducted to validate the somatic mutations. Clinical characteristics and genotype-phenotype correlations were analyzed. Results Among the 32 patients, 17 were males and 15 were females, with the age ranging from 2 months to 13 years. Nineteen cases （59.3%） were classified as cesioflammea type Ⅱa, 10 cases （31.3%） as cesioflammea type Ⅱb, and 3 cases （9.4%） as unclassified type. Vascular lesions involving > 20% of the total body surface area （BSA） were observed in 28 patients （87.5%）, while pigmentary lesions involving > 20% of the BSA were present in 13 （40.6%）. Regarding vascular manifestations, all patients had congenital capillary malformations; 16 patients （50.0%） were accompanied by nevus anemicus, 2 patients （6.3%） by infantile hemangioma, and 1 patient （3.1%） by pyogenic granuloma. Pigmentary lesions predominantly involved the trunk （30 cases, 93.8%）, with ectopic Mongolian spots being the most common （31 cases, 96.9%）, followed by café-au-lait macules （8 cases, 25.0%） and nevus of Ota （5 cases, 15.6%）. Extracutaneous manifestations were observed in 27 patients （84.4%）, with scleral melanocytosis being the most common （22 cases, 68.8%）. Limb or soft tissue overgrowth was present in 13 cases （40.6%）, and glaucoma in 5 （15.6%）. Comorbid conditions included Klippel-Trénaunay syndrome, Sturge-Weber syndrome accompanied by Klippel-Trénaunay syndrome, diffuse capillary malformation with overgrowth, and scoliosis. Genetic testing was performed in 24 patients, and somatic GNA11/GNAQ gene mutations were identified in 22 （91.7%）, including GNA11 c.547C>T （p.R183C） in 15 cases, GNA11 c.547C>A （p.R183H） in 1 case, and GNAQ c.548G>A （p.R183Q） in 6 cases. Scleral melanocytosis was more common in patients with GNA11 mutations （14/16） than in those with GNAQ mutations （1/6; P = 0.004）. Conclusion In this study, the cesioflammea type was the most common subtype of phakomatosis pigmentovascularis in children, and phakomatosis pigmentovascularis was usually characterized by extensive vascular involvement; somatic mutations in the GNA11/GNAQ genes were commonly identified; scleral melanocytosis was more common in patients with GNA11 mutations than in those with GNAQ mutations.

Key words: Vascular malformations, Phakomatosis pigmentovascularis, Congenital capillary malformation, Ectopic Mongolian spots, GNA11 gene, GNAQ gene, Somatic mutation