Clinical features and genetic analysis of two Chinese pedigrees affected with Lymphedema-Distichiasis syndrome
10.3760/cma.j.cn511374-20240807-00426
- VernacularTitle:淋巴水肿-双行睫综合征2个家系的临床特征及遗传学分析
- Author:
Jing LI
1
;
Limin YUAN
1
;
Shanshan ZHAI
1
;
Naiqi LI
1
;
Handuo WANG
1
;
Xiao HAN
1
;
Lanlan ZHAO
1
;
Juan LI
1
;
Shihong CUI
1
;
Ling LIU
1
Author Information
1. 郑州大学第三附属医院医学遗传与产前诊断科 郑州 450052
- Publication Type:Journal Article
- Keywords:
Lymphedema-distichiasis syndrome;
Fetal period;
FOXC2 gene;
Prenatal diagnosis;
Genetic counseling
- From:
Chinese Journal of Medical Genetics
2024;41(12):1441-1447
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene. Methods:A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords "Lymphedema-Distichiasis syndrome" and " FOXC2". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No.2021-046-01). Results:Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c. 361C>T (p.R121C) variant and a c. 168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified. Conclusion:The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c. 168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.
