ESPE Abstracts

Objective: Type E brachydactyly (BDE) is characterized by shortening of the metacarpal/metatarsal bones, with the phalanges also potentially affected. This study analyzes the clinical features and genotype-phenotype correlations of BDE in children.

Methods: This study selected 135 patients with BDE who visited the Children's Hospital affiliated with Soochow University from June 2021 to December 2023 and completed a bone age X-ray examination. The study collected initial and follow-up clinical data of the patients. Peripheral blood samples were collected from the patients and their parents for whole-exome sequencing (WES). Potentially pathogenic variants identified were validated using Sanger sequencing. Patients were grouped according to different clinical phenotypes, and the genotype-phenotype correlations were compared to between groups. Statistical analysis was performed using SPSS 26.0 software. A P-value <0.05 was considered statistically significant.

Results: A total of 135 children with BDE were included in the study, comprising 116 girls (85.9%) and 19 boys (14.1%). The overall prevalence of BDE was 0.22%, with a prevalence of 0.35% in girls and 0.07% in boys. The main reasons for visiting were breast enlargement (27%) and health check-ups (27%), followed by slow growth (22%) and the onset of menstruation (14%). Seventy-two patients (53%) had isolated BDE, with only metacarpal/metatarsal shortening and no involvement of the phalanges. The remaining patients had both metacarpal/metatarsal and phalangeal shortening. Sixty patients agreed to complete genetic testing. According to the variant classification guidelines of the ACMG, pathogenic or likely pathogenic variants were found in 31.7% (19/60) of the patients. We identified gene mutations in 15 patients (78.9%), and another 4 patients (21.1%) had pathogenic/likely pathogenic CNVs. The most common gene mutations were found in GNAS (n = 4), followed by EXT1 (n = 2) and ACAN (n = 2). Other gene mutations included PRMT7 (n = 1), POGZ (n = 1), PTHLH (n = 1), NPR2 (n = 1), IHH (n = 1), PRKARlA (n = 1), and FBXW11 (n = 1). There were statistically significant differences in the positive rates of genetic testing between groups classified by predicted adult height, the number of shortened metacarpal/metatarsal bones, distinctive facial features, and intellectual disabilities.

Conclusion: The prevalence of BDE is approximately 1 in 500, with a higher occurrence in females than in males. Patients with multiple shortened metacarpal/metatarsal bones, distinctive facial features, intellectual disabilities, or with predicted short adult stature, are more likely to carry genetic mutations. Patients who are predicted to have normal adult height with no other systemic abnormalities typically are tested negative for genetic mutations.