Hypophosphatemic rickets and craniosynostosis: a multicenter case series

Vega, Rafael A.; Opalak, Charles; Harshbarger, Raymond J.; Fearon, Jeffrey A.; Ritter, Ann M.; Collins, John J.; Rhodes, Jennifer

doi:10.3171/2015.10.peds15273

Cited by 62 publications

(84 citation statements)

References 24 publications

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“…In the proximal kidney tubules, it transports hydrogen ions to the endosomes and chloride ions outside, which helps to maintain proper pH values. 26 31 Due to disturbances to anatomy and the structure of teeth, including impaired mineralisation of tooth enamel, abnormal dentine maturation, enlarged tooth pulp cavity and increased permeability of dental tissues for pathogenic bacteria, periodontal abscesses form that are typical of hypophosphatemic rickets. 16 Adults additionally experience frequent skeletal pain caused by osteomalacia, osteoarthrosis and pathological fractures.…”

Section: Autosomal Recessive Hypophosphatemic Ricketsmentioning

confidence: 99%

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

Michałus

Rusińska

2018

Clinical Genetics

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Apart from the classic forms of rickets, there are rare genetic disorders from the group of vitamin D-resistant rickets where the clinical picture is very similar to the classic forms. Diagnosis of genetically conditioned rickets is often delayed. It is very important to know that a disorder of genetic background may be the cause of the failure of classic treatment in patients with rachitic symptoms. In the group of genetically conditioned rickets there are, among others, congenital hypophosphatemic rickets and vitamin D-dependent rickets type I and II. Congenital hypophosphatemic rickets is characterised by bone mineralisation disturbances related to hypophosphatemia secondary to renal loss of phosphates. The term "hypophosphatemic rickets" covers a group of diseases with similar phenotype but with different genotypes, inheritance models and etiopathogeneses. Mutation of at least 10 genes underlying this disease entity has been described. Vitamin D-dependent rickets are caused by defects of vitamin D metabolism. There are 4 forms described in literature that are distinguished by their genetic causes: type 1A (vitamin D-dependent rickets type IA), type 1B (vitamin D-dependent rickets type IB) and type 2A (vitamin D-dependent rickets type 2A), type 2B (vitamin D-dependent rickets type 2B). A detailed family history in combination with a physical examination, biochemistry and X-ray imaging helps in differential diagnostics of rare forms of rickets.

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Section: Autosomal Recessive Hypophosphatemic Ricketsmentioning

confidence: 99%

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

Michałus

Rusińska

2018

Clinical Genetics

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“…Craniosynostosis and Chiari malformations may occur. (31,34,35) During growth, the leg length is disproportionately affected compared with the trunk length, and despite treatment, patients fail to have catchup growth during puberty, actually decreasing height Z-scores during this time and are often short as adults. (36) Additional complications of XLH include enthesopathy, osteoarthritis, pseudofractures, and dental abscesses.…”

Section: Fgf23 and Hypophosphatemiamentioning

confidence: 99%

FGF23, Hypophosphatemia, and Emerging Treatments

2019

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FGF23 is an important hormonal regulator of phosphate homeostasis. Together with its co‐receptor Klotho, it modulates phosphate reabsorption and both 1α‐hydroxylation and 24‐hydroxylation in the renal proximal tubules. The most common FGF23‐mediated hypophosphatemia is X‐linked hypophosphatemia (XLH), caused by mutations in the PHEX gene. FGF23‐mediated forms of hypophosphatemia are characterized by phosphaturia and low or low‐normal calcitriol concentrations, and unlike nutritional rickets, these cannot be cured with nutritional vitamin D supplementation. Autosomal dominant and autosomal recessive forms of FGF23‐mediated hypophosphatemias show a similar pathophysiology, despite a variety of different underlying genetic causes. An excess of FGF23 activity has also been associated with a number of other conditions causing hypophosphatemia, including tumor‐induced osteomalacia, fibrous dysplasia of the bone, and cutaneous skeletal hypophosphatemia syndrome. Historically phosphate supplementation and therapy using analogs of highly active vitamin D (eg, calcitriol, alfacalcidol, paricalcitol, eldecalcitol) have been used to manage conditions involving hypophosphatemia; however, recently a neutralizing antibody for FGF23 (burosumab) has emerged as a promising treatment agent for FGF23‐mediated disorders. This review discusses the progression of clinical trials for burosumab for the treatment of XLH and its recent availability for clinical use. Burosumab may have potential for treating other conditions associated with FGF23 overactivity, but these are not yet supported by trial data. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…XLHR children are at risk to develop cranial vault and craniovertebral anomalies of potential neurosurgical interest, namely early closure of the cranial sutures and Chiari type 1 malformation. Though the association of craniosynostosis to rickets has been documented as early as 1964 and several reports of scaphocephaly in patients with rickets have been described, the literature on craniosynostosis and Chiari type I malformations occurring in patients with XLHR remains scarce, limited only to some case reports and very few case series …”

Section: Introductionmentioning

confidence: 99%

“…Though the association of craniosynostosis to rickets has been documented as early as 1964 and several reports of scaphocephaly in patients with rickets have been described, (16) the literature on craniosynostosis and Chiari type I malformations occurring in patients with XLHR remains scarce, limited only to some case reports and very few case series. (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) The aim of our retrospective study was to determine the incidence and characteristics of cranial and craniovertebral anomalies in a large series of children with X-linked hypophosphatemic rickets.…”

Section: Introductionmentioning

confidence: 99%

High Incidence of Cranial Synostosis and Chiari I Malformation in Children With X-Linked Hypophosphatemic Rickets (XLHR)

Rothenbühler

Fadel

Debza

et al. 2018

Journal of Bone and Mineral Research

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X‐linked hypophosphatemic rickets (XLHR) represents the most common form of genetic hypophosphatemia and causes rickets and osteomalacia in children because of increased FGF23 secretion and renal phosphate wasting. Even though cranial vault and craniovertebral anomalies of potential neurosurgical interest, namely early closure of the cranial sutures and Chiari type I malformation, have been observed in children with XLHR, their actual incidence and characteristics are not established. The aims of this study were to analyze the incidence of cranial and cervico‐occipital junction (COJ) anomalies in children with XLHR and describe its features. This is a retrospective study of CT scans of the head and skull in 44 XLHR children followed at the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism. Forty‐four children with XLHR, 15 boys and 29 girls, aged 8.7 ± 3.9 years at time of CT scan, were studied. We found that 59% of XLHR children had a complete or partial fusion of the sagittal suture and 25% of XLHR children showed protrusion of the cerebellar tonsils. A history of dental abscesses was associated with craniosynostosis, and craniosynostosis was associated with abnormal descent of cerebellar tonsils. Only 2 patients showed neurologic symptoms. Four of 44 patients (9%) required neurosurgery. This study highlights that sagittal suture fusion and Chiari type I malformation are frequent complications of XLHR. The incidence of sagittal synostosis in XLHR is actually extremely high and was probably underestimated so far. Chiari type I malformation is also frequent. Because diagnosis of craniovertebral anomalies can be underestimated on a purely clinical basis, radiological studies should be considered in XLHR children if a proper diagnosis is warranted. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

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Hypophosphatemic rickets and craniosynostosis: a multicenter case series

Cited by 62 publications

References 24 publications

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

FGF23, Hypophosphatemia, and Emerging Treatments

High Incidence of Cranial Synostosis and Chiari I Malformation in Children With X-Linked Hypophosphatemic Rickets (XLHR)

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