Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome

Yunting Lin; Xiaohong Chen; Bobo Xie; Zhihong Guan; Xiaodan Chen; Xiuzhen Li; Peng Yi; Rong Du; Huifen Mei; Li Liu; Wen Zhang; Chunhua Zeng

doi:10.3389/fgene.2023.1085210

Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome

Front Genet. 2023 Mar 21:14:1085210. doi: 10.3389/fgene.2023.1085210. eCollection 2023.

Authors

Yunting Lin¹, Xiaohong Chen², Bobo Xie^{3

4}, Zhihong Guan¹, Xiaodan Chen¹, Xiuzhen Li¹, Peng Yi¹, Rong Du¹, Huifen Mei¹, Li Liu¹, Wen Zhang¹, Chunhua Zeng¹

Affiliations

¹ Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
² Department of Endocrinology and Metabolism, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Center for Medical Genetics and Genomics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁴ The Guangxi Health Commission Key Laboratory of Medical Genetics and Genomics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.

Abstract

Objective: Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the KMT2A gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH). Methods: Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis. Results: In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the KMT2A gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age. Conclusion: Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the KMT2A gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.

Keywords: Chinese; KMT2A gene; Wiedemann-Steiner syndrome; clinical characteristics; genetic spectrum; therapeutic effect.

Grants and funding

This work was supported by the Research Fund of Guangzhou Science and Technology Innovation Commission (grant numbers 202102080455 and 202102020133) and the Joint Research Fund of Guangdong Basic and Applied Basic Research Commission (grant number 2021A1515220168).