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Growth charts in FGFR2- and FGFR3-related faciocraniosynostoses
Caroline Ea1, Quentin Hennocq1, Arnaud Picard1
1Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker - Enfants Malades, Assistance Publique - Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France.
Insights
Patients with Faciocraniosynostoses (FCS) due to Fibroblast Growth Factor Receptor (FGFR) mutations show significantly reduced height and weight. Early endocrine assessment may benefit these patients with extra-cranial growth anomalies.
Area of Science:
- Genetics and Developmental Biology
- Pediatric Endocrinology
- Craniofacial Surgery
Background:
- Faciocraniosynostoses (FCS) result from premature closure of skull sutures, often caused by activating Fibroblast Growth Factor Receptor (FGFR) mutations.
- Activating FGFR3 mutations also cause osteochondrodysplasia (OCD), affecting growth plate cartilage.
- The presence of extra-cranial growth anomalies in FCS patients with FGFR mutations is hypothesized.
Purpose of the Study:
- To investigate the prevalence and pattern of extra-cranial growth anomalies in patients with FGFR-related FCS.
- To determine if specific age periods are associated with reduced growth parameters in these patients.
- To evaluate the potential benefit of endocrine assessment for managing growth issues in FGFR-related FCS.
Main Methods:
- Retrospective collection of height and weight data from 70 patients with FGFR-related FCS.
- Data collected from patients admitted between 2000 and 2021 to the Craniofacial Unit at Necker - Enfants Malades University Hospital.
- Comparison of growth parameters against control data.
Main Results:
- Patients with FGFR-related FCS exhibited significantly reduced height and weight compared to controls.
- Lower height and weight values were observed in two distinct age groups: 1-3 years and over 8 years.
- Growth hormone treatment did not normalize height and weight in four treated patients.
Conclusions:
- FGFR-related FCS is associated with clinically significant extra-cranial growth anomalies.
- Current management protocols may not adequately address these growth issues.
- Systematic pre-pubertal endocrine assessment is recommended for patients with FGFR-related FCS.
- Findings support the hypothesis that activating FGFR mutations impact both membranous ossification and long bone development.
Objective:
Faciocraniosynostoses (FCS) are malformations affecting the development of the bones of the skull and face, due to the premature closure of one or more craniofacial sutures, mostly secondary to activating Fibroblast Growth Factor Receptor (FGFR) 1-3 mutations. Gain-of-function FGFR3 mutations are also responsible for various conditions referred to as osteochondrodysplasia (OCD), characterized by structural and functional abnormalities of growth plate cartilages. We hypothesized that patients with FGFR-related faciocraniosynostoses may present extra-cranial growth anomalies.
Study Design:
We retrospectively collected height and weight data from a cohort of 70 patients. Included patients were admitted for FGFR-related FCS between 2000 and 2021 at the Craniofacial Unit of Necker - Enfants Malades University Hospital in Paris, France.
Results:
We showed that FGFR-related faciocraniosynostoses had significantly reduced heights and weights relative to controls, and that two specific time periods (1-3 years and > 8 years of age) were associated with lower height and weight values. Four patients had received growth hormone treatment but remained below normal values for growth in height and weight.
Conclusions:
Patients with FGFR-related faciocraniosynostoses have clinically significant extra-cranial anomalies which are not currently investigated and managed in usual protocols; these patients could benefit from a systematic pre-pubertal endocrine assessment. More generally, our results extend the scope of extracranial anomalies in FGFR-related faciocraniosynostoses and support the hypothesis that all conditions with activating FGFR mutations affect both membranous ossification and long bones.
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