Clinical, genetic, and pathological analysis in 165 children with disorders of sex development
CAO Yan-Yan1,2, ZANG Ke-Xin2, LIU Ying-Ye1,2, ZHANG Qiang2,3, ZHOU Yun2,4, ZHANG Shuang5, XIA Yao-Fang2,6, LIU Lei2,7, CHEN Xiao-Xiao2,3, ZHAO Shi-Meng2,4, LIU Li-Jun2,3, CUI Xiao-Wei2
1.Department of Endocrinology, Genetics and Metabolism, Children's Hospital of Hebei Province, Shijiazhuang 050031, China 2.Children's Hospital of Hebei Province/Pediatric Clinical Research Centre for Child Health and Disorders of Hebei Province, Shijiazhuang 050031, China
Abstract：Objective To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). Methods A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. Results Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. Conclusions Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.
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