Liang Yan,Lyu Yiqing,Xu Zihan,et al.Significance of 2D:4D digit ratio in the assessment of children with disorders of sex development[J].Journal of Clinical Pediatric Surgery,,():526-533.[doi:10.3760/cma.j.cn101785-20260306-00092]
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Significance of 2D:4D digit ratio in the assessment of children with disorders of sex development

Journal of Clinical Pediatric Surgery[ISSN:1671-6353/CN:43-1380/R] volume: Number: 2026 06 Page: 526-533 Column: 专题·性发育异常的诊治 Date of publication: 2026-06-26
Author(s):
Liang Yan1; 2;  Lyu Yiqing1; 2;  Xu Zihan1;  Huang Yichen1;  Li Pin2; 3;  Chen Fang1; 2
1. Department of Urology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China;
2. Difference of Sex Development Center, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China;
3. Department of Endocrinology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200062, China
Keywords:
Disorder of Sex Development; Diagnosis;  Differential; Symptom Assessment; Second-to-fourth Digit Length Ratio; Masculinization Programming Window; Androgens
DOI:
10.3760/cma.j.cn101785-20260306-00092
Abstract:
Objective To explore the relationship between second-to-fourth digit ratio (2D:4D) and sex hormone levels during masculinization programming window (MPW) through analyzing children with different types of disorders of sex development (DSD) and evaluate the potential value of 2D:4D as an auxiliary diagnostic indicator for DSD. Methods For this prospective study,137 DSD children hospitalized from October 2023 to February 2026 were enrolled as observation group.Copies of both hands were preserved.Based upon disease type,they were assigned into 6 categories of 21-hydroxylase deficiency (n=21),5α-reductase deficiency (n=12),17α-hydroxylase deficiency (n=6),bilateral gonadal dysgenesis (n=11),complete androgen insensitivity syndrome (n=18) and Klinefelter syndrome (n=9).During the same period,male children diagnosed as phimosis/hydrocele (n=30) and female children diagnosed as appendicitis/indirect inguinal hernia (n=30) were enrolled as normal control group.Copies of both hands from all affected cases should be retained.The lengths of index and ring fingers of each individual were independently measured by two physicians.2D∶4D ratio for each hand was calculated and mean value (M 2D∶4D) utilized for statistical analysis.Wilcoxon signed-rank test was employed for comparing left and right 2D∶4D within the same individual.Mann-Whitney U test was employed for comparing M 2D∶4D between two groups and Kruskal-Wallis test for comparing M 2D∶4D among multiple groups.Post-hoc pairwise comparisons were performed with Dunn’s test. Results No statistically significant difference existed between left and right 2D∶4D ratios (P=0.230).A statistically significant difference in M 2D∶4D was noted between normal males and normal females (P=0.010).Kruskal-Wallis test revealed no significant difference in M 2D∶4D between children with 17α-hydroxylase deficiency and either normal male or normal female children (P>0.05).With the exception of individuals with 17α-hydroxylase deficiency,all other disease categories in observation group showed statistically significant differences in M 2D∶4D as compared to both normal males and normal females (P<0.05).Specifically,children with 46,XX 21-hydroxylase deficiency exhibited a significantly lower M 2D∶4D than normal females (P<0.001).No significant difference existed in M 2D∶4D between children with 5α-reductase deficiency and normal males (P>0.05).Children with gonadal dysgenesis,complete androgen insensitivity syndrome (CAIS) and Klinefelter syndrome all demonstrated significantly higher M 2D∶4D ratios than normal males (P<0.05). Conclusion 2D∶4D ratio may serve as an exploratory tool for examining hormone profiles during Mini-Puberty of Infancy (MPW) in DSD children with distinct 2D∶4D patterns corresponding to different etiologies of DSD.As a stable indicator reflecting androgen exposure during MPW period,2D∶4D ratio may be utilized as useful reference in auxiliary diagnostic evaluation of DSD children.

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Memo

收稿日期:2026-3-6。
基金项目:上海市 2024 年度"科技创新行动计划"医学创新研究领域项目(24Y12800700)
通讯作者:吕逸清,Email:tristan_ren@hotmail.com

Last Update: 1900-01-01