HOLT-ORAM SINDROM - ZNAČAJ RANE DIJAGNOZE
Apstrakt
Uvod: Holt-Oram sindrom (HOS) je genetski sindrom. Nasleđuje se autosomno-dominantno.Bolest nastaje zbog mutacije gena TBX5 (T-box) na dugom kraku hromozoma 12 (12q24.1), važnog za razvoj srca i gornjih ekstremiteta. Incidenca je 1:100 000 novorođenčadi i spada u retke bolesti. Karakteriše se malformacijama gornjih ekstremiteta-displazija šake (nedostatak palca, trifalangealni palac, nemogućnost pozicije palca) i defekt radijusa ili ulne, izuzetno sa fokomelijom. Izraženost pojedinih simptoma u spektru kliničke slike Holt-Oram sindroma izraženija je ako je majka nosilac mutacije. Uz Holt-Oram sindrom se opisuju srčane mane. Najčešća srčana mana je defekt atrijalnog septuma (ASD).
Prikaz slučaja: U radu je prikazan devetogodišnji dačak koji je primljen u Dečije odeljenje Zdravstvenog centra Zaječar radi ispitivanja malog rasta. Pri kliničkom pregledu, pored malog rasta se zapaža karakterističan fenotip. Ima deformitet palca desne šake i hipoplaziju radijusa. Na srcu se auskultacijom registruje sistolni šum. Potvrđena je dijagnoza Holt-Oram sindroma. Ultrazvučnim pregledom srca utvrđen je atrijalni septalni defect (ASD). Predloženu operaciju na srcu roditelji odbijaju.
Zaključak: Uloga neonatologa je da u slučaju anomalija palca šake ili gornjih ekstremiteta posumnja i na moguću srčanu manu i da roditelje uputi na dalje multidisciplinarno ispitivanje koje uključuje i molekularno-genetičko ispitivanje. Pravovremena stručna pomoć roditeljima već u porodilištu, uz upućivanje na kvalitetno multidisciplinarno ispitivanje i praćenje, osnova je savremenog zbrinjavanja novorođenčeta rođenog sa retkom bolešću.
Reference
Mary Holt and Samuel Oram. Familial heart disease with skeletal malformations. Br Heart J. 1960 Apr;22(2):236-42. PMID: 14402857, PMCID: PMC1017650
Charles A. Goldfarb, Lindley B. Wall. HOLT-ORAM SY. Journal of Hand Surgery, 2014 , Vol 39, Issue 8, P1646-1648.
G Virdis, M Dessole, S Dessole, G Ambrosini, E Cosmi, P L Cherchil, G Capobianco. Holt Oram syndrome: a case report. Clin Exp Obstet Gynecol. 2016;43(1):137-9. PMID: 27048037
Binoy Shankar, MD, Euden Bhutia, MD, Dinesh Kumar, MD, Sunil Kishore, MD, and Shakti Pad Das, MD. Holt-Oram Syndrome: A Rare Variant. Iran J Med Sci. 2017 Jul; 42(4): 416–419. PMCID: PMC5523052, PMID: 28761211
Clémence Vanlerberghe, Anne-Sophie Jourdain, Jamal Ghoumid and all. Holt-Oram syndrome: clinical and molecular description of 78 patients with TBX5 variants. Eur J Hum Genet. 2019 Mar; 27(3): 360–368. PMCID: PMC6460573 PMID: 30552424
Guan-nan He, Xue-yan Wang, Min Kang, Xi-min Chen, Na Xi, Jing Zhao, and Xi Chen. Prenatal Diagnosis of Holt–Oram Syndrome With a Novel Mutation of TBX5 Gene: A Case Report. Front Pediatr. 2021; 9: 737633. https://doi.org/10.3389/fped.2021.737633
Sarah Obican, Lindsay Maggio. Holt-Oram Syndrome. Obstetric Imaging: Fetal Diagnosis and Care (Second Edition), 2018, Pages 557-559 DOI:10.1016/B978-0-323-44548-1.00132-7 8. Camille Cenni, Stephanie Andres, Maja Hempel and all. TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/ulnar-mammary syndrome phenotype. Eur J Med Genet. 2021 Jul;64(7):104213.PMID: 33930582, DOI: 10.1016/j.ejmg.2021.104213
Xu Qin, Wang Wei, and Gong Fangqi. Horseshoe Lung Associated With Holt-Oram Syndrome. Iran J Pediatr. 2015 Apr; 25(2). PMCID: PMC4505999, PMID: 26195995
Ayokunle Osonuga, Jeffrey K. Arhin, Gloria C. Okoye, and Adebayo Da’Costa. Possible Holt-Oram Syndrome: Missed Prenatal Diagnosis and Sub-Optimal Management in a Poor-Resourced Hospital. Balkan Medical Journal (Vol. 36, Issue 3), May 2019. PMCID: PMC6528524, PMID: 30873826
Won Kyoung Jhang, Beom Hee Lee, Gu-Hwan Kim and all. Clinical and molecular characterisation of Holt-Oram syndrome focusing on cardiac manifestations. Cardiol Young. 2015 Aug; 25(6):1093-8. PMID: 25216260, DOI: 10.1017/S1047951114001656
Marilena Renata Spiridon, Antoniu Octavian Petris and all. Holt-Oram Syndrome With Multiple Cardiac Abnormalities. Cardiol Res. 2018 Oct; 9(5): 324–329.PMCID: PMC6188042, PMID: 30344832
Marilena Renata Spiridon 1, Antoniu Octavian Petris 1 2, Eusebiu Vlad Gorduza and all. Holt-Oram Syndrome With Multiple Cardiac Abnormalities. Cardiol Res. 2018 Oct;9(5):324-329. PMID: 30344832, PMCID: PMC6188042, DOI: 10.14740/cr767w
Paweł Tyczyński, Ilona Michałowska, Barbara Miłosz-Wieczorek, Piotr Hoffman, Adam Witkowski. Holt-Oram syndrome, bicuspid aortic valve, and patent ductus arteriosus. Kardiol Pol 2021;79(12):1395-1396. PMID: 34599494, DOI: 10.33963/KP.a2021.0118
Paweł Tyczyński, Ilona Michałowska, Barbara Miłosz-Wieczorek, Piotr Hoffman, Adam Witkowski. Holt-Oram syndrome, bicuspid aortic valve, and patent ductus arteriosus. Polish Heart Journal, Vol 79, No 12 (2021).PMID: 34599494, DOI: 10.33963/KP.a2021.0118
Igor Stefanović, Aleksa Milić , Kristina Matejić , Ida Jovanović. Successful surgical closure of an aortopulmonary window associated with Holt-Oram syndrome in adulthood. Vojnosanit Pregl 2018; 75(7): 730–733 https://doi.org/10.2298/VSP160926361S
F. D. Tucker, J. K. Morris and all. EUROCAT: an update on its functions and activities. J Community Genet. 2018 Oct; 9(4): 407–410.PMCID: PMC6167264, PMID: 29736796
Edin Međedović, Amer Iglica, Nedim Begić, Mahmutbegović Emir. Holt–Oram Syndrome: The Importance of Prenatal Detection. Donald School Journal of Ultrasound in Obstetrics and Gynecology. May 2020. 14(2):172-174.DOI:10.5005/jp-journals-10009-1644
Ingeborg Barisic, Ljubica Boban, Ruth Greenlees and all. Holt Oram syndrome: a registry-based study in Europe. Orphanet J Rare Dis. 2014; 9: 156. PMCID: PMC4245183, PMID: 25344219
