RESUMO
BACKGROUND: Craniosynostosis is an underdiagnosed complication associated with hypophosphatemic rickets. The study aims to describe the clinical and auxological characteristic of children with hypophosphatemic rickets and craniosynostosis, describe the usual treatment, and compare the characteristics with those of children without craniosynostosis. METHODS AND PATIENTS: An observational and retrospective cohort study was conducted. Clinical notes and cranial images were reviewed. Out of 96 children, only the 50 patients who had skull images were included. RESULTS: Out of 50 patients, 26 (15 males) had craniosynostosis (52%). No differences were observed in birth size, age, height, body proportions, alkaline phosphatase, serum phosphate, or percent tubular reabsorption of phosphate at first appointment among children with or without craniosynostosis. Among patients with craniosynostosis, dolichocephaly was prevalent. The sagittal suture was affected in all patients with craniosynostosis, with 19 of 26 children (73%) affected with isolated scaphocephaly. Pan-sutural craniosynostosis was present in 7 children (27%). None of the children had microcephaly, 7 of them presented macrocephaly and, in the remaining subjects, head circumference was normal. Five patients had undergone at least 1 cranial remodeling surgery. One patient with craniosynostosis was diagnosed with a Chiari I malformation. Molecular characterization of PHEX gene was performed in 14 cases. CONCLUSIONS: Craniosynostosis is an underdiagnosed complication of hypophosphatemic rickets. Many patients with normal head size and growth may go undiagnosed, thus it is important to consider this association for early diagnosis and possible surgical treatment. A multidisciplinary approach is necessary for a correct long-term follow-up.
Assuntos
Craniossinostoses/patologia , Raquitismo Hipofosfatêmico Familiar/complicações , Predisposição Genética para Doença , Mutação , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Criança , Pré-Escolar , Craniossinostoses/etiologia , Craniossinostoses/metabolismo , Craniossinostoses/cirurgia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
Abstract: cranial sutures are specialized structures composed of the sutural mesenchyme, the overlying scalp, the dura and osteogenic fronts. Each one of these structures express important proteins for osteogenic maturation, membranous ossification of skull bones, and homeostasis of cranial sutures in a differential, spatial and temporal manner. These proteins include fibroblast growth factor (FGF) and its receptors (FGFR), the transforming growth factor beta (TGF-beta), bone morphogenetic proteins (BMPs), as well as transcription factors TWIST and MSX2, among others. The alteration in the expression of one or more of these proteins causes multiple pathological conditions; one of them is the premature closure of one or more cranial sutures, known as craniosynostosis. This malformation is commonly treated with surgery. However, advances in the fields of molecular and cellular biology have allowed to conduct research on some proteins involved in the development of craniosynostosis. The results of these studies can lead to future preventive therapeutic strategies that may be used as a complement to the surgical treatment of craniosynostosis. Possible strategies include the use of specific drugs that can regulate the expression and activation of FGF signaling pathways, TGF-beta or BMPs, to prevent or avoid craniosynostosis or re-synostosis after a surgery.
Resumen: las suturas craneales son estructuras especializadas compuestas por el mesénquima sutural, el pericráneo suprayacente, la duramadre y los frentes osteogénicos. Cada una de estas estructuras expresan de forma diferencial, espacial y temporalmente, proteínas importantes para la maduración osteogénica, la osificación membranosa de los huesos calvarios y la homeostasis de las suturas craneales. Estas proteínas incluyen el factor de crecimiento fibroblástico (FGF) y sus receptores (FGFR), el factor de crecimiento transformante beta (TGF-beta), las proteínas morfogenéticas óseas (BMPs), así como factores de transcripción TWIST y MSX2, entre otros. La alteración en la expresión de una o varias de estas proteínas provoca múltiples condiciones patológicas, una de ellas es el cierre prematuro de una o varias suturas craneales, conocido como craneosinostosis. Esta malformación es comúnmente tratada con cirugía. Sin embargo, los avances en los campos de la biología molecular y celular han permitido investigar algunas proteínas que participan en el desarrollo de la craneosinostosis. Los resultados de estos estudios pueden generar futuras estrategias terapéuticas preventivas o que complementen los tratamientos quirúrgicos de la craneosinostosis. Algunas estrategias posibles son el uso de fármacos específicos que puedan regular la expresión y activación de las vías de señalización del FGF, el TGFbeta o de las BMPs, para prevenir la craneosinostosis o evitar la resinostosis tras una cirugía.