The incidence and clinical characteristics of fragile X syndrome in China

Lianni Mei; Chunchun Hu; Dongyun Li; Ya Wang; Huiping Li; Kaifeng Zhang; Bingrui Zhou; Ruoping Zhu; Randi J Hagerman; Xiu Xu; Qiong Xu

doi:10.3389/fped.2023.1064104

The incidence and clinical characteristics of fragile X syndrome in China

Front Pediatr. 2023 Feb 13:11:1064104. doi: 10.3389/fped.2023.1064104. eCollection 2023.

Authors

Lianni Mei¹, Chunchun Hu¹, Dongyun Li¹, Ya Wang², Huiping Li¹, Kaifeng Zhang¹, Bingrui Zhou¹, Ruoping Zhu², Randi J Hagerman^{3

4}, Xiu Xu¹, Qiong Xu¹

Affiliations

¹ Department of Child Health Care, Children's Hospital of Fudan University, Shanghai, China.
² Department of Child Health Care, Anhui Provincial Children's Hospital, Hefei, China.
³ The MIND Institute, University of California Davis Medical Center, Sacramento, CA, United States.
⁴ Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA, United States.

Abstract

Introduction: Fragile X syndrome (FXS) is a X-linked neurodevelopmental disorder (NDD). This study aims to investigate the incidence of FXS in Chinese children and analyze the comprehensive clinical characteristics of these FXS children.

Methods: Children diagnosed with idiopathic NDD were recruited between 2016 and 2021 from the department of Child Health Care, Children's Hospital of Fudan University. We combined tetraplet-primed PCR-capillary electrophoresis and whole exome sequencing (WES)/panel or array-based comparative genomic hybridization (array-CGH) to identify the size of the CGG repeats and the mutations or copy number variations (CNVs) in the genome and in FMR1. The clinical features of FXS children were analyzed according to pediatricians' recording, parental questionnaires, the results of examinations and follow-up.

Results: The incidence of FXS in Chinese children with idiopathic NDD was 2.4% (42/1753) and in those with FXS, 2.38% had a deletion (1/42). Here, we present the clinical characteristics of 36 children with FXS. Overweight was observed in two boys. The average intelligence quotient (IQ)/development quotient (DQ) of all FXS patients was 48. The average ages of meaningful words and walking alone were 2 years and 10 months and 1 year and 7 months, respectively. The most frequent repetitive behavior was stimulated by hyperarousal to sensory stimulation. On social aspects, social withdrawal, social anxiety, and shyness accounted for 75%, 58%, and 56% of the total number of children, respectively. Approximately 60% of FXS children in this cohort were emotionally labile and prone to temper tantrums. Self-injury and aggression toward others could also be observed, at 19% and 28%, respectively. The most frequent behavioral problem was attention-deficit hyperactivity disorder (ADHD) seen in 64% and the most common facial features were a narrow and elongated face and large or prominent ears in 92% of patients.

Discussion: Screening of FMR1 full mutation provides the possibility for patients' further medical supports and the clinical features of FXS children obtained in this study will increase the understanding and diagnosis of FXS.

Keywords: FXS; NDD; children; clinical characteristics; incidence.

Grants and funding

This study was supported by the Key Subject Construction Project of Shanghai Municipal Health Commission (No.shslczdzk02903) and Foreign Expert Program of Ministry of Science and Technology (No.G2022132004l).