Growth charts in FGFR2- and FGFR3-related faciocraniosynostoses
Caroline Ea,
Quentin Hennocq,
Arnaud Picard,
Michel Polak,
Corinne Collet,
Laurence Legeai-Mallet,
Éric Arnaud,
Giovanna Paternoster,
Roman Hossein Khonsari
Affiliations
Caroline Ea
Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France
Quentin Hennocq
Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France
Arnaud Picard
Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France
Michel Polak
Service d'endocrinologie, gynécologie et diabétologie pédiatriques, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France
Corinne Collet
Unité fonctionnelle de génétique moléculaire, Département de génétique DMU BioGeM, Hôpital Robert-Debré, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France; Biologie de l'os et du cartilage, INSERM UMR 1132, Paris, France
Laurence Legeai-Mallet
Imagine Institute, Molecular and Physiopathological Bases of Osteochondrodysplasia, INSERM UMR 1163, Paris, France
Éric Arnaud
Unité fonctionnelle de chirurgie craniofaciale, Service de neurochirurgie pédiatrique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France; Centre de Référence Maladies Rares Craniosténoses et Malformations Craniofaciales (CRANIOST), Filière Maladies Rares TeteCou, France
Giovanna Paternoster
Unité fonctionnelle de chirurgie craniofaciale, Service de neurochirurgie pédiatrique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France; Centre de Référence Maladies Rares Craniosténoses et Malformations Craniofaciales (CRANIOST), Filière Maladies Rares TeteCou, France
Roman Hossein Khonsari
Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France; Unité fonctionnelle de chirurgie craniofaciale, Service de neurochirurgie pédiatrique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Faculté de Médecine, Université Paris Cité, Paris, France; Centre de Référence Maladies Rares Craniosténoses et Malformations Craniofaciales (CRANIOST), Filière Maladies Rares TeteCou, France; Corresponding author at: Service de chirurgie maxillo-faciale et chirurgie plastique, Hôpital Necker – Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
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.
