Брой 2/2023, Статии

Моногенни краниосиностози – основни генетични характеристики и клинични случаи

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Т. Делчев1, Цв. Велева1,2, М. Средкова1, Д. Авджиева-Тзавелла1,2

1Отделение по клинична генетика, СБАЛДБ. Катедра по Педиатрия към Медицински факултет на Медицински Университет – София
2Катедра по педиатрия, Медицински университет – София

Резюме

Краниосиностозата е процес на преждевременна осификация и облитерация на един или повече от черепно-мозъчните шевове. Това води до ограничен обем на черепа с невъзможност за анатомична акомодация на нарастващите вътречерепни тъкани и органи. В резултат се оформя краниална деформация, лицев дисморфизъм и повишен вътречерепен натиск. Общата честота на този краниален дефект е около 1 на 2500 новородени деца.

Краниосиностозата се разделя на синдромна (20% от случаите) и несиндромна (80% от случаите). Около 1/3 от случаите на синдромна краниосиностоза се дължат на дефекти в определени гени – FGFR1, FGFR2, FGFR3, CD96, EFNB1, FLNA, GLI3, IHH, MSX2, POR, RAB21, RECQL4, SKI, SOX9, TGFBR1, TGFBR2 и TWIST1 – т.нар. моногенни краниосиностози. Те се предават, с малки изключения (RAB21), по автозомно-доминантен механизъм. Отличават се с характерен дисморфизъм, но също така и с вариабилна експресивност.

Във фокуса на тази статия попадат три случая на моногенна краниосиностоза: клиничен случай А – дете със синдром на Saethre-Chotzen, клиничен случай В – дете със синдром на Pfeiffer и клиничен случай С – дете с Краниофронтоназална дисплазия.

Ключови думи: моногенна, краниосиностоза, TWIST1, FGFR, EFNB1

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Библиография

  1. Бояджиев С, Янева Н, Симеонов Е: Молекулярна генетика на краниосиностозата. Сп. Педиатрия Том 4, 2015, 3–14
  2. Cohen MM, MacLean RE: Craniosynostosis: Diagnosis, Evaluation, and Management, 2nd ed. Oxford, Oxford University Press, 2000.
  3. Gorlin RJ, Cohen MM Jr, Hennekam RCM: Syndromes of the Head and Neck, 4th ed. (Oxford Monographs on Medical Genetics. Vol. 42). Oxford, Oxford University Press, 2001.
  4. Jehee FS, Krepischi-Santos AC, Rocha K.M, et al., High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridization, J Med Genet 2008;45:447–450. doi:10.1136/jmg.2007.057042
  5. Wilkie A, Byren C, Hurst J.A, et al. – Prevalence and Complications of Single-Gene and Chromosomal Disorders in Craniosynostosis, American Academy of Pediatrics, April 2010, doi:10.1542/peds.2009-3491
  6. Passos-Bueno M.R, Sertié A, Jehee FS, et al. Genetics of Craniosynostosis: Genes, Syndromes, Mutations and Genotype-Phenotype Correlations. Front Oral Biol. Basel, Karger, 2008, 12: 107–143
  7. Currarino G, Sagittal synostosis in X-linked hypophosphatemic rickets and related diseases. Pediatr Radiol 2007 37:805-812
  8. Zollino M, Lattante S, Orteschi D, et al. Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples. Front. Neurosci. 2017, 11:587. doi: 10.3389/fnins.2017.00587
  9. Cunningham ML, Seto ML, Ratisoontorn C, et al. Syndromic craniosynostosis: from history to hydrogen bonds. Orthod Craniofac Res. 2007 May;10(2):67-81. doi: 10.1111/j.1601-6343.2007.00389.
  10. Galbiati S, Stenirri S, Sbaiz L, et al. Identification of an 18 bp deletion in the TWIST1 gene by CO-amplification at lower denaturation temperature-PCR (COLD-PCR) for non-invasive prenatal diagnosis of craniosynostosis: first case report. Clin Chem Lab Med 2014; 52: 505-509.
  11. Massalska D, Bijok J, Kucińska-Chahwan A, et al. Prenatal diagnosis of craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3-7p15.3, including TWIST1 gene–a case report. Ginekol Pol 2014; 85: 541-544.
  12. Cai J, Goodman BK, Patel AS, et al. Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening. Hum Genet. 2003 Dec;114(1):68-76. doi: 10.1007/s00439-003-1012-7.
  13. de Heer IM, de Klein A, van den Ouweland AM, et al. Clinical and genetic analysis of patients with Saethre-Chotzen syndrome. Plast Reconstr Surg. 2005 Jun;115(7):1894-902; discussion 1903-5. doi: 10.1097/01.prs.0000165278.72168.51.
  14. Spaggiari E, Aboura A, Sinico M, et al. Prenatal diagnosis of a 7p15-p21 deletion encompassing the TWIST1 gene involved in Saethre-Chotzen syndrome. Eur J Med Genet 2012; 55: 498-501.
  15. Gebb J, Demasio K, Dar P. Prenatal sonographic diagnosis of familial Saethre-Chotzen syndrome. J Ultrasound Med 2011; 30: 420-422.
  16. Das J.M, Winters R. Pfeiffer Syndrome. GeneReviews Jul 2022, https://www.ncbi.nlm.nih.gov/books/NBK532882/
  17. Rai R, Iwanaga J, Dupont G, et al. Pfeiffer type 2 syndrome: review with updates on its genetics and molecular biology. Childs Nerv Syst. 2019 Feb 11. doi: 10.1007/s00381-019-04082-7
  18. Glaser RL, Jiang W, Boyadjiev SA, et al. Paternal origin of FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome. Am J Hum Genet 2000, 66: 768–777.
  19. Medina M, Cortes E, Eguiluz I, et al.Three-dimensional features of Pfeiffer syndrome. Int J Gynaecol Obs 2009; 105: 266-267
  20. Greig AV, Wagner J, Warren SM, et al. Pfeiffer syndrome: analysis of a clinical series and development of a classification system. J Craniofac Surg (2013)24: 204–215.
  21. Khonsari RH, Way B, Nysjц J, et al. Fronto-facial advancement and bipartition in Crouzon-Pfeiffer and Apert syndromes: impact of fronto-facial surgery upon orbital and airway parameters in FGFR2 syndromes. J Craniomaxillofac Surg (2016) 44: 1567–1575.
  22. Spruijt B, Rijken BF, den Ottelander BK, et al. First vault expansion in Apert and Crouzon-Pfeiffer syndromes: front or back? Plast Reconstr Surg (2016)137: 112e–121e.
  23. Pfeiffer RA. [Dominant Hereditary Acrocephalosyndactylia]. Z Kinderheilkd. 1964 Sep 16; 90:301-20. [https://www.ncbi.nlm.nih.gov/books/NBK532882/]
  24. van den Elzen ME, Twigg SR, Goos JA, et al. Phenotypes of craniofrontonasal syndrome in patients with a pathogenic mutation in EFNB1. Eur J Hum Genet (2014). 22: 995–1001
  25. Twigg SR, Kan R, Babbs C, et al. Mutations of ephrin- B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. Proc Natl Acad Sci USA 2004; 101:8652– 8657.
  26. Kawamoto HK, Heller JB, Heller MM, et al. Craniofrontonasal dysplasia: a surgical treatment algorithm. Plast Reconstr Surg (2007) 120: 1943–1956.

Адрес за кореспонденция:

Отделение по Клинична генетика, СБАЛДБ – ЕАД “Проф. Иван Митев”, Медицински университет – София,  

бул. “Иван Гешов”, 11  

1431, София 

e-mail: trayan_delchev@abv.bg