ОПЫТ СОЧЕТАННОГО ПРИМЕНЕНИЯ ХИРУРГИЧЕСКОГО ЛЕЧЕНИЯ И ТАРГЕТНОЙ ТЕРАПИИ У РЕБЕНКА С CLOVES-СИНДРОМОМ
Клинический случай
Дата публикации: ноября 14, 2024
Ключевые слова
PIK3CA
PROS
избыточный рост
лимфатическая мальформация
PROS
избыточный рост
лимфатическая мальформация
Аннотация
CLOVES – синдром (OMIM #612918) является одним из вариантов PIK3CA ассоциированных поражений спектра синдромов избыточного роста. Заболевания, относящиеся к спектру синдромов избыточного роста (PROS - PIK3CA-Related Overgrowth Spectrum) является в настоящий момент малоизученной гетерогенной группой патологических состояний, характеризующихся наличием врождённых липоматозных разрастаний, сосудистых мальформаций, эпидермальных невусов и скелетных аномалий. Свойственный PROS мозаицизм обуславливает широчайший спектр клинических проявлений, затрудняет своевременную диагностику. Оперативное лечение пациентов с диагнозом PROS связано с высокой частотой рецидивов и необходимостью проведения повторных многократных оперативных вмешательств. В представленном клиническом наблюдении молекулярно-генетическое исследование операционного материала позволило подтвердить наличие мутации гена PIK3CA и назначить консервативную терапию ингибитором фосфатидилинозитол-3-киназы - алпелисиб, улучшить качество жизни пациента и избавить его от многократных оперативных вмешательств.Литература
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2. Parker VER. et al. Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum // Genet Med. – 2019. – V. 21. – No. 5. – P. 1189-1198. doi: 10.1038/s41436-018-0297-9.
3. Reynolds G. et al. Epidemiology of the disorders of the Pik3ca-related overgrowth spectrum (Pros) // Eur J Hum Genet. – 2023. – V. 31. – No. 11. – P. 1333-1336. DOI: 10.1038/s41431-023-01414-9.
4. Keppler-Noreuil KM. et al. Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies // Am J Med Genet C Semin Med Genet. – 2016. – V. 172. – No. 4. – P. 402-421. doi: 10.1002/ajmg.c.31531.
5. Hillmann P. et al. PI3K/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases // Int J Mol Sci. – 2019. – V. 20. – No. 22. – P. 5792. doi: 10.3390/ijms20225792.
6. Mirzaa G. et al. PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution // JCI Insight. – 2016. - V. 1. – No. 9. – P. e87623. doi: 10.1172/jci.insight.87623.
7. Brioude F. et al. Overgrowth syndromes - clinical and molecular aspects and tumour risk // Nat Rev Endocrinol. – 2019. – V. 15. – No. 5. – P. 299-311. doi: 10.1038/s41574-019-0180-z.
8. Keppler-Noreuil KM. et al. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation // Am J Med Genet A. – 2015. – V. 167A. – No. 2. – P. 287-95. doi: 10.1002/ajmg.a.36836.
9. Lalonde E. et al. Molecular diagnosis of somatic overgrowth conditions: A single-center experience // Mol Genet Genomic Med. – 2019. – V. 7. – No. 3. – P. e536. doi: 10.1002/mgg3.536.
10. Ten Broek RW. et al. Comprehensive molecular and clinicopathological analysis of vascular malformations: A study of 319 cases // Genes Chromosomes Cancer. - 2019. – V. 58. – No. 8. – P. 541-550. doi: 10.1002/gcc.22739.
11. Hughes M. et al. PIK3CA vascular overgrowth syndromes: an update // Curr Opin Pediatr. – 2020. – V. 32. – No. 4. – P. 539-546. doi: 10.1097/MOP.0000000000000923.
12. Martinez-Lopez A. et al. CLOVES syndrome: review of a PIK3CA-related overgrowth spectrum (PROS) // Clin Genet. – 2017. – V. 91. – No. 1. – P. 14-21. doi: 10.1111/cge.12832.
13. Uller W. et al. Overgrowth syndromes with complex vascular anomalies // Semin Pediatr Surg. – 2014. – V. 23. – No. 4. – P. 208-15. doi: 10.1053/j.sempedsurg.2014.06.013.
14. Markham A. Alpelisib: First Global Approval // Drugs. – 2019. – V. 79. – No. 11. – P. 1249-1253. doi: 10.1007/s40265-019-01161-6.
15. Venot Q. et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome // Nature. – 2018. – V. 558. – No. 7711. – P. 540-546. doi: 10.1038/s41586-018-0217-9.
16. López Gutiérrez JC. et al. Alpelisib Treatment for Genital Vascular Malformation in a Patient with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, and Spinal/Skeletal Anomalies and/or Scoliosis (CLOVES) Syndrome // J Pediatr Adolesc Gynecol. – 2019. – V. 32. – No. 6. – P. 648-650. doi: 10.1016/j.jpag.2019.07.003.
17. Garneau AP. et al. Somatic non-cancerous PIK3CA-related overgrowth syndrome treated with alpelisib in North America // J Mol Med (Berl). – 2021. – V. 99. – No. 3. – P. 311-313. doi: 10.1007/s00109-020-02030-6.
18. Canaud G. et al. Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS) // Genet Med. – 2023. – V. 25. – No. 12. – P. 100969. doi: 10.1016/j.gim.2023.100969.