Base of Skull & Spinal Canal Narrowing in an Adolescent with Autosomal Recessive Hypophosphatemic Rickets Type 2

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is an uncommon hereditary form of rickets characterised by chronic renal phosphate loss and impaired bone mineralisation. This results from compound heterozygous or homozygous pathogenic variants in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), a key producer of extracellular inorganic pyrophosphate (PPi) and an inhibitor of fibroblast growth factor23 (FGF23). ENPP1 deficiency impacts FGF23 and increases its activity. Inactivating ENPP1 variants are associated with both Generalised Arterial Calcification of Infancy (GACI) and ARHR2, even within the same family. Both conditions share a deficiency of ENPP1, displaying clinical variability without a clear genotype-phenotype correlation. Whilst pathogenic ENPP1 variants are known to be associated with various phenotypes, including vascular calcification, hearing loss, ossification of the posterior longitudinal ligament (OPLL), and pseudoxanthoma elasticum (PXE), skull changes have not been reported to our knowledge. We present herein a case of a 10-year-old girl with ARHR2, due to compound heterozygous pathogenic ENPP1 variants, who was found to have papilledema on a routine eye test. Neuroimaging revealed enlarged lateral ventricles, compression of the spinal cord at the foramen magnum with Chiari 1 malformation and a retroverted odontoid peg. She underwent two endoscopic third ventriculostomy procedures to manage the hydrocephalus and a further foramen magnum decompression procedure to alleviate her headaches and neck pain concerns. Individuals with ARHR2 may experience alterations at the base of the skull, potentially leading to base of skull narrowing, chronic hydrocephalus, and Chiari malformation.