Cutaneous skeletal hypophosphatemia syndrome: the first clinical description of two cases with genetic verification in Russia
https://doi.org/10.25557/2073-7998.2023.06.51-61
Abstract
Cutaneous-skeletal hypophosphatemia syndrome (CSHS) or Epidermal nevus syndrome (ENS) associated with hypophosphatemic rickets is a rare variation of hypophosphatemic rickets caused by phosphate wasting due to elevated fibroblast growth factor-23 (FGF23) as a result of somatic gain‐of‐function variants in the HRAS, NRAS, or KRAS genes. Clinical symptoms of CSHS, besides rickets, are congenital epidermal, melanocytic and sebaceous nevus as well as focal bone lesions ipsilateral to nevus. What makes genetic diagnosis of this condition extremely problematic is the necessity of location of mutations in the affected tissues (bones, epidermis). Such patients have a high risk of becoming disabled due to severe hypotonia, osteomalacia, bone fractures and difficulties associated with treatment of severe hypophosphatemia. The first two clinical cases of two unrelated patients with such condition have been performed in Russia. Both patients have CSHS confirmed by genetic testing.
About the Authors
K. S. Kulikova
Research Centre for Medical Genetics; National Medical Research Center for Endocrinology
Russian Federation
Russian Federation
Kulikova Kristina
1, Moskvorechye st., Moscow, 115522
11, Dm. Ulyanova st., Moscow, 117036
E. N. Raikina
National Medical Research Center for Endocrinology
Russian Federation
Russian Federation
11, Dm. Ulyanova st., Moscow, 117036
E. R. Tolmacheva
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after V.I.Kulakov, of the Ministry of Healthcare of Russian Federation
Russian Federation
Russian Federation
4, Oparina st., Moscow, 117997
E. A. Pomerantseva
National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after V.I.Kulakov, of the Ministry of Healthcare of Russian Federation
Russian Federation
Russian Federation
4, Oparina st., Moscow, 117997
References
1. Aschinberg L.C., Solomon L.M., Zeis P.M., Justice P., Rosenthal I.M. Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions. J Pediatr. 1977;91(1):56–60.
2. Avitan-Hersh E., Tatur S., Indelman M. et al. Postzygotic HRAS mutation causing both keratinocytic epidermal nevus and thymoma and associated with bone dysplasia and hypophosphatemia due to elevated FGF23. J Clin Endocrinol Metab. 2014;99 (1):E132-6. doi: 10.1210/jc.2013-2813.
3. Ovejero D., Lim Y.H., Boyce A.M. et al. Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural history, and treatment. Osteoporos Int. 2016;27(12):3615-3626. doi: 10.1007/s00198-016-3702-8.
4. de Castro L.F., Ovejero D., Boyce A.M. Diagnosis of endocrine disease: mosaic disorders of FGF23 excess: fibrous dysplasia/Mc-Cune-albright syndrome and cutaneous skeletal hypophosphatemia syndrome. Eur. J. Endocrinol. 2020; 182 (5):R83-R99;
5. Huynh C., Gillis A., Fazendin J., Abdullatif H. A case report to assess the safety and efficacy of Burosumab, an investigational antibody to FGF23, in a single pediatric patient with Epidermal Nevus Syndrome and associated hypophosphatemic rickets. Bone Rep. 2022;17:101605. doi: 10.1016/j.bonr.2022.101605.
6. Khadora M., Mughal M.Z. Burosumab treatment in a child with cutaneous skeletal hypophosphatemia syndrome: A case report. Bone Rep. 2021;15:101138. doi: 10.1016/j.bonr.2021.101138.
7. Merz L.M., Buerger F., Ziegelasch N. et al. A Case Report: First Long-Term Treatment With Burosumab in a Patient With Cutaneous-Skeletal Hypophosphatemia Syndrome. Front Endocrinol (Lausanne). 2022;13:866831. doi: 10.3389/fendo.2022.866831.
8. Sugarman J., Maruri A., Hamilton D.J. et al. The efficacy and safety of burosumab in two patients with cutaneous skeletal hypophosphatemia syndrome. Bone. 2023;166: 116598, https://doi.org/10.1016/j.bone.2022.116598.
9. Richards S., Aziz N., Bale S., et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. doi: 10.1038/gim.2015.30.
10. Ryzhkova O.P., Kardymon O.L., Prohorchuk E.B., et al. Rukovodstvo po interpretatsii dannykh posledovatel’nosti DNK cheloveka, poluchennykh metodami massovogo parallel’nogo sekvenirovaniya (MPS) (redaktsiya 2018, versiya 2) [Guidelines for the interpretation of massive parallel sequencing variants (update 2018, v2)]. Meditsinskaya genetika [Medical Genetics]. 2019;18(2):3-23. (In Russ.) https://doi.org/10.25557/2073-7998.2019.02.3-23
11. Rauen K.A. The RASopathies. Annual review of genomics and human genetics. 2013;14:355–69. doi: 10.1146/annurevgenom-091212-153523.
12. Kulikova K.S., Tiulpakov A.N. Gipofosfatemicheskiy rakhit: patogenez, diagnostika i lecheniye. [Hypophosphatemic rickets: pathogenesis, diagnosis and treatment]. Ozhireniye i metabolizm. [Obesity and metabolism]. 2018;15(2):46-50. (In Russ.) https://doi.org/10.14341/omet9672
13. Lim Y.H., Ovejero D., Sugarman J.S., et al. Multilineage Somatic Activating Mutations in HRAS and NRAS Cause Mosaic Cutaneous and Skeletal Lesions, Elevated FGF23 and Hypophosphatemia. Hum Mol Genet. 2014; 23(2):397–407. doi: 10.1093/hmg/ddt429
14. Shimada T., Urakawa I., Yamazaki Y., et al. FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. Biochem. Biophys. Res. Commun. 2004;314:409–414.
15. Shimada T., Hasegawa H., Yamazaki Y., et al. FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis. J Bone Miner Res. 2004;19: 429-435. https://doi.org/10.1359/JBMR.0301264
16. Lim Y.H., Ovejero D., Derrick K.M.; Yale Center for Mendelian Genomics; Collins M.T., Choate K.A. Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a multilineage somatic mosaic RASopathy. J Am Acad Dermatol. 2016;75(2):420-7. doi:10.1016/j.jaad.2015.11.012.
17. Carpenter T.O., Whyte M.P., Imel E.A., Boot A.M., Högler W., Linglart A., et al. Burosumab Therapy in Children With X-Linked Hypophosphatemia. N Engl J Med. 2018; 378(21):1987–98. doi: 10.1056/nejmoa1714641.
18. Carli D., Cardaropoli S., Tessaris D., et al. Successful treatment with MEK-inhibitor in a patient with NRAS-related cutaneous skeletal hypophosphatemia syndrome. Genes Chromosomes Cancer. 2022; 61(12):740-746. doi: 10.1002/gcc.23092.
19. Ershov N.M., Pshonkin A.V., Mareeva Yu.M., et al. Pervyy opyt primeneniya MEK-ingibitorov pri neyrofibromatoze I tipa u detey v Rossiyskoy Federatsii v usloviyakh statsionara kratkovremennogo lecheniya natsional’nogo meditsinskogo issledovatel’skogo tsentra [The first experience of using MEK inhibitors for type 1 neurofibromatosis in children in the Russian Federation in a hospital for short-term treatment at the National Medical Research Center]. Rossiyskiy zhurnal detskoy gematologii i onkologii [Russian Journal of Pediatric Hematology and Oncology]. 2021;8(1):85-92. (In Russ.) https://doi.org/10.21682/2311-1267-2021-8-1-85-92.
20. Zutt M., Strutz F., Happle .R, et al. Schimmelpenning-Feuerstein-Mims syndrome with hypophosphatemic rickets. Dermatology. 2003;207(1):72-6. doi: 10.1159/000070948.
Review
For citations:
Kulikova K.S., Raikina E.N., Tolmacheva E.R., Pomerantseva E.A. Cutaneous skeletal hypophosphatemia syndrome: the first clinical description of two cases with genetic verification in Russia. Medical Genetics. 2023;22(6):51-61. (In Russ.) https://doi.org/10.25557/2073-7998.2023.06.51-61
Views:
588
Email this article 