Clinical features and variant spectrum of FGFR3-related disorders.
10.7499/j.issn.1008-8830.2504002
- Author:
Shi-Li GU
1
;
Ling-Wen YING
1
;
Guo-Ying CHANG
1
;
Xin LI
1
;
Juan LI
1
;
Yu DING
1
;
Ru-En YAO
;
Ting-Ting YU
;
Xiu-Min WANG
1
Author Information
1. Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
- Publication Type:Journal Article
- Keywords:
Achondroplasia;
Child;
Fibroblast growth factor receptor 3;
Genetic variant;
Skeletal dysplasia
- MeSH:
Humans;
Receptor, Fibroblast Growth Factor, Type 3/genetics*;
Child;
Male;
Child, Preschool;
Female;
Infant;
Adolescent;
Dwarfism/genetics*;
Achondroplasia/genetics*;
Lordosis/genetics*;
Infant, Newborn;
Retrospective Studies;
Genetic Association Studies;
Bone and Bones/abnormalities*;
Phenotype;
Limb Deformities, Congenital
- From:
Chinese Journal of Contemporary Pediatrics
2025;27(10):1259-1265
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders.
METHODS:Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH).
RESULTS:Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge.
CONCLUSIONS:ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
