Juvenile Paget’s disease with compound heterozygous mutations in TNFRSF11B presenting with recurrent clavicular fractures and a mild skeletal phenotype

Naot, Dorit, Wilson, Louise C., Allgrove, Jeremy, Adviento, Eleanor, Piec, Isabelle ORCID: https://orcid.org/0000-0002-0648-1330, Musson, David S., Cundy, Tim and Calder, Alistair D. (2020) Juvenile Paget’s disease with compound heterozygous mutations in TNFRSF11B presenting with recurrent clavicular fractures and a mild skeletal phenotype. Bone, 130. ISSN 8756-3282

[thumbnail of Accepted_Manuscript]
Preview
PDF (Accepted_Manuscript) - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (2MB) | Preview

Abstract

Juvenile Paget’s disease (JPD) is a rare recessively-inherited bone dysplasia. The great majority of cases described to date have had homozygous mutations in TNFRSF11B, the gene encoding osteoprotegerin. We describe a boy who presented with recurrent clavicular fractures following minor trauma (8 fractures from age 2 to 11). He was of normal height and despite mild lateral bowing of the thighs and anterior bowing of the shins he remained physically active. Abnormal modelling was noted in ribs and humeri on clavicular radiographs, and a skeletal survey at the age of 7 showed generalised diaphyseal expansion of the long bones with thickening of the periosteal and endosteal surfaces of the cortices. On biochemical evaluation, serum alkaline phosphatase was noted to be persistently elevated. The diagnosis of JPD was confirmed by the finding of compound heterozygous mutations in TNFRSF11B: a maternally-inherited A > G missense mutation at position 1 of the first amino acid codon (previously reported) and a paternally-inherited splice acceptor site mutation in intron 3 at a highly conserved position (not previously reported). Bioinformatics analysis suggested both mutations were disease-causing. Compound heterozygote mutations in TNFRSF11B causing JPD have been previously reported only once – in a boy who also had a relatively mild skeletal phenotype. The milder features may lead to delay in diagnosis and diagnostic confusion with other entities, but the extraskeletal features of JPD may nonetheless develop.

Item Type: Article
Uncontrolled Keywords: bones,dysplasia,idiopathic hyperphosphatasia,juvenile paget's disease,mutation,osteoprotegerin-deficiency,osteoprotegerin,tnfrsf11b
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 31 Oct 2019 15:43
Last Modified: 06 Jun 2024 15:08
URI: https://ueaeprints.uea.ac.uk/id/eprint/72830
DOI: 10.1016/j.bone.2019.115098

Downloads

Downloads per month over past year

Actions (login required)

View Item View Item