X-linked hypophosphatemia
X-linked hypophosphatemia (XLH) is an inherited disorder characterized by low levels of phosphate in the blood. Phosphate levels are low because phosphate is abnormally processed in the kidneys, which causes a loss of phosphate in the urine (phosphate wasting) and leads to soft, weak bones (rickets)
XLH patients may also be affected by premature, complete, or partial ossification of sutures between cranial bone, which could eventually result in cranial dysmorphia, decreased intracranial volume, and secondary abnormally high intracranial pressure with a cerebral compression. Our goal is to address the criteria and the management of the skeletal complications associated with XLH, mainly orthopedic and neurosurgical care, and reflect on decision-making and follow-up complexities. 1).
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. 2).
A 7 year-old twin girl with hypophosphataemic rickets was evaluated for a recent onset of mild strabismus.She was a homozygous twin sister with hypophosphataemic rickets diagnosed at the age of 2 years, with a mutation in intron 21 of the PHEX gene, which was also present in her sister.The girls' clinical histories were remarkable for an important lower limb varus that progressively improved after starting phosphate supplementation with a galenical solution (Joulies solution 1 mmol phosphate/ml) and vitamin D 1,25 OH.During the examinations, both girls were in good general condition. Physical examinations were unremarkable, except for tibial varus, bilateral fifth finger clinodactyly and bilateral syndactyly of the third and fourth foot fingers. No major head shape abnormalities were noticeable except for a high forehead.One patient presented with a slight strabismus, normal isochoric isocyclic and reactive pupils, no signs of cranial nerve deficit, and no alterations in the rest of the neurological examination. An ophthalmological evaluation showed bilateral papilloedema. A cerebral MRI scan was then performed, suspecting elevated intracranial pressure (figure 1). The same examination was performed on the asymptomatic sister which also demonstrated papilloedema with similar findings on cranial MRI too. edpract;107/2/124/BLKF1F1BLK_F1Figure 1Sagittal MR T1-weighted imaging shows a 12 mm cerebellar tonsillar herniation (shown by the white arrow) and bulb-medullary junction herniation. The apex of the epistropheus tooth almost reaches the occipital clivus (shown by the white line) and imprints the bulb. QUESTIONS: Which is the most likely diagnosis?CraniosynostosisPseudotumor cerebriDrusenArnold-Chiari malformationHow should these patients be managed?Acetazolamide treatmentThird to fourth ventricle cystostomyWait and see with periodical visual evoked potential follow-upNeurosurgeryHow should patients with X linked hypophosphataemic rickets (XLH rickets) be managed for the risk of craniosynostosis?Monitor cephalic anthropometric measuresPerform a MRI scan if clinical signs of craiosynostosis or intracranial hypertension are presentPerform a skull X-ray every 2 yearsPerform an MRI scan every 2 years 3).
Careful monitoring of head shape and growth is therefore critical for early detection of craniosynostosis in XLH. 4)
Rothenbuhler et al. 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. 5).
X-linked hypophosphatemia (XLH) is the most common inherited form of renal phosphate wasting and inherited rickets. Patients have hyperplasia of fibrochondrocytes in tendons and ligaments, causing the structures to thicken and calcify. Thickening of the lamina, hypertrophy of facet joints, and calcification of spinal ligaments are sequelae of this condition and can result in central or foraminal stenosis that compresses nerve roots or the spinal cord 6).
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