Hereditary multiple exostoses (HME) is a rare autosomal dominant disorder, caused primarily by loss of function mutations in 2 genes EXT1 and EXT2 linked to the synthesis of heparan sulfate (HS). Deficiency of HS causes the formation of numerous benign cartilage-capped bone tumours. There is no causal treatment for this disease. Surgery is recommended only for symptomatic lesions and malignant transformations.

Case Report:
The case is presented of an 11-year-old boy with a pathogenic variant in the EXT1 gene and steroid-sensitive nephrotic syndrome (NS), diagnosed at the age of 8. There are only single reports of the co-existence of HME and NS. Conceivably, HS deficiency may explain ultra-structural changes in kidney glomeruli that result in NS, although unknown, contributions. Further research is necessary.

Szawłoga T, Strzoda A, Sobieszczańska A. A rare case of coexistence of hereditary multiple exostoses and steroid-sensitive nephrotic syndrome. J Pre-Clin Clin Res. 2013; 17(3): 195–197. doi: 10.26444/jpccr/168133
DuBose CO. Multiple Hereditary Exostoses. Radiol Technol. 2016;87(3):305–21. quiz 322-5.
Beltrami G, Ristori G, Scoccianti G, et al. Hereditary Multiple Exostoses: a review of clinical appearance and metabolic pattern. Clin Cases Miner Bone Metab. 2016;13(2):110–118. doi:10.11138/ccmbm/2016.13.2.110.
D’Arienzo A, Andreani L, Sacchetti F, et al. Hereditary Multiple Exostoses: Current Insights. Orthop Res Rev. 2019;11:199–211. doi:10.2147/ORR.S183979.
Roberts IS, Gleadle JM. Familial nephropathy and multiple exostoses with exostosin-1 (EXT1) gene mutation. J Am Soc Nephrol. 2008 Mar;19(3):450–3. doi:10.1681/ASN.2007080842.
Jia X, Yamamura T, Gbadegesin R, et al. Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome. Kidney Int. 2020;98(5):1308–1322. doi:10.1016/j. kint.2020.05.029.
Watts AJB, Keller KH, Lerner G, et al. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology. J Am Soc Nephrol. 2022;33(1):238–252. doi:10.1681/ASN.2021060794.
Khalil R, Boels MGS; PALGA Group, et al. Mutations in the heparan sulfate backbone elongating enzymes EXT1 and EXT2 have no major effect on endothelial glycocalyx and the glomerular filtration barrier. Mol Genet Genomics. 2022;297(2):397–405. doi:10.1007/s00438-022-01854-w.
Chen S, Wassenhove-McCarthy DJ, Yamaguchi Y, et al. Loss of heparan sulfate glycosaminoglycan assembly in podocytes does not lead to proteinuria. Kidney Int. 2008;74(3):289–299. doi:10.1038/ki.2008.159.
Ravindran A, Casal Moura M, Fervenza FC, et al. In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes. J Am Soc Nephrol. 2021;32(3):695–706. doi:10.1681/ASN.2020081181.
Bharati J, Tiewsoh K, Dawman L, et al. Long-term complications in patients with childhood-onset nephrotic syndrome. Pediatr Nephrol. 2023;38(4):1107–1113. doi:10.1007/s00467-022-05693-0.
Bukowska-Olech E, Trzebiatowska W, Czech W, et al. Hereditary Multiple Exostoses-A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies. Front Genet. 2021;10;12:759129. doi:10.3389/fgene.2021.759129.
Journals System - logo
Scroll to top