“…Beyond abnormal skull shape, craniosynostosis and defective mineralisation in XLH patients can be associated with Arnold-Chiari malformations, which may cause central nervous system problems [193] . Hypophosphatemic rickets has long been linked to craniosynostosis [194], but the relationship is poorly understood [195]. Fig.…”
Background
X-linked hypophosphatemia (XLH) is an inherited disease of phosphate metabolism in which inactivating mutations of the
Phosphate Regulating Endopeptidase Homolog, X-Linked
(
PHEX
) gene lead to local and systemic effects including impaired growth, rickets, osteomalacia, bone abnormalities, bone pain, spontaneous dental abscesses, hearing difficulties, enthesopathy, osteoarthritis, and muscular dysfunction. Patients with XLH present with elevated levels of fibroblast growth factor 23 (FGF23), which is thought to mediate many of the aforementioned manifestations of the disease. Elevated FGF23 has also been observed in many other diseases of hypophosphatemia, and a range of animal models have been developed to study these diseases, yet the role of FGF23 in the pathophysiology of XLH is incompletely understood.
Methods
The role of FGF23 in the pathophysiology of XLH is here reviewed by describing what is known about phenotypes associated with various PHEX mutations, animal models of XLH, and non-nutritional diseases of hypophosphatemia, and by presenting molecular pathways that have been proposed to contribute to manifestations of XLH.
Results
The pathophysiology of XLH is complex, involving a range of molecular pathways that variously contribute to different manifestations of the disease. Hypophosphatemia due to elevated FGF23 is the most obvious contributor, however localised fluctuations in tissue non-specific alkaline phosphatase (TNAP), pyrophosphate, calcitriol and direct effects of FGF23 have been observed to be associated with certain manifestations.
Conclusions
By describing what is known about these pathways, this review highlights key areas for future research that would contribute to the understanding and clinical treatment of non-nutritional diseases of hypophosphatemia, particularly XLH.
“…Beyond abnormal skull shape, craniosynostosis and defective mineralisation in XLH patients can be associated with Arnold-Chiari malformations, which may cause central nervous system problems [193] . Hypophosphatemic rickets has long been linked to craniosynostosis [194], but the relationship is poorly understood [195]. Fig.…”
Background
X-linked hypophosphatemia (XLH) is an inherited disease of phosphate metabolism in which inactivating mutations of the
Phosphate Regulating Endopeptidase Homolog, X-Linked
(
PHEX
) gene lead to local and systemic effects including impaired growth, rickets, osteomalacia, bone abnormalities, bone pain, spontaneous dental abscesses, hearing difficulties, enthesopathy, osteoarthritis, and muscular dysfunction. Patients with XLH present with elevated levels of fibroblast growth factor 23 (FGF23), which is thought to mediate many of the aforementioned manifestations of the disease. Elevated FGF23 has also been observed in many other diseases of hypophosphatemia, and a range of animal models have been developed to study these diseases, yet the role of FGF23 in the pathophysiology of XLH is incompletely understood.
Methods
The role of FGF23 in the pathophysiology of XLH is here reviewed by describing what is known about phenotypes associated with various PHEX mutations, animal models of XLH, and non-nutritional diseases of hypophosphatemia, and by presenting molecular pathways that have been proposed to contribute to manifestations of XLH.
Results
The pathophysiology of XLH is complex, involving a range of molecular pathways that variously contribute to different manifestations of the disease. Hypophosphatemia due to elevated FGF23 is the most obvious contributor, however localised fluctuations in tissue non-specific alkaline phosphatase (TNAP), pyrophosphate, calcitriol and direct effects of FGF23 have been observed to be associated with certain manifestations.
Conclusions
By describing what is known about these pathways, this review highlights key areas for future research that would contribute to the understanding and clinical treatment of non-nutritional diseases of hypophosphatemia, particularly XLH.
“…Early and severe cases tend to have more extensive craniosynostosis. 18,19 Our patient developed secondary craniosynostosis with mild proptosis after he was treated with vitamin D and calcium supplements. However, he did not develop signs of increased intracranial pressure, and no surgical intervention was deemed necessary.…”
“…Over the years, x-ray examination became increasingly more common and more important in the diagnosis and classification of craniostenosis, as stated by Fairman in 1948 [ 14 ]: “The x-ray examination enables us to determine with accuracy the variety of craniostenosis and the degree of contraction of the skull”; moreover, they were used in order to perform diagnostic tests, such as ventriculography, and post-surgical studies [ 10 ]. Many papers, describing cases of different types of craniosynostosis, classifications and treatment, showed the application of radiological imaging in diagnostic management [ 16 , 17 , 18 , 19 , 20 ]. Radiological examinations were used also in case of secondary craniosynostosis, for example in a case report about a case of vitamin D-resistant rickets needing a decompressive craniotomy [ 19 ].…”
Section: Past (1950–1980): Not Only the Physical Exammentioning
confidence: 99%
“…Many papers, describing cases of different types of craniosynostosis, classifications and treatment, showed the application of radiological imaging in diagnostic management [ 16 , 17 , 18 , 19 , 20 ]. Radiological examinations were used also in case of secondary craniosynostosis, for example in a case report about a case of vitamin D-resistant rickets needing a decompressive craniotomy [ 19 ]. X-rays showed classical signs of rickets in wrists, limbs and thorax, and the skull presented with increased impressions and a prominence in the sagittal plane, the coronary suture was hardly visible, and the other sutures were small.…”
Section: Past (1950–1980): Not Only the Physical Exammentioning
Craniosynostosis, the premature closure of cranial sutures, is one of the principal causes of pediatric skull deformities. It can cause aesthetic, neurological, acoustic, ophthalmological complications up to real emergencies. Craniosynostosis are primarily diagnosed with accurate physical examination, skull measurement and observation of the deformity, but the radiological support currently plays an increasingly important role in confirming a more precise diagnosis and better planning for therapeutic interventions. The clinician must know how to diagnose in the earliest and least invasive way for the child. In the past, technological limitations reduced the choices; today, however, there are plenty of choices and it is necessary to use the various types of available imaging correctly. In the future, imaging techniques will probably rewrite the common classifications we use today. We provide an updated review of the role of imaging in this condition, through the ages, to outline the correct choice for the clinician for an early and non-invasive diagnosis.
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