medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.01.3-11medgen-2237Research ArticleНАУЧНЫЕ ОБЗОРЫREVIEWСиндром Вольфа–Хиршхорна: этиология, патогенез, клиника, особенности симптоматической терапии и анестезиологического пособия, пренатальная диагностика (обзор литературы)Wolf–Hirschhorn syndrome: etiology, pathogenesis, clinic, features of symptomatic therapy and anesthesia, prenatal diagnosis (review)КосиноваЕ. И.KosinovaE. I.

Елена Игоревна Косинова

302028

Октябрьская ул., д. 4

Орёл

Elena I. Kosinova

302028

4, Oktyabrskaya st.

Orel

elena_kosinov@mail.ruЗубцоваТ. И.ZubtsovaТ. I.

302026

ул. Комсомольская д. 95

Орел

302026

95, Komsomolskaya st.

Orel

ПолшведкинаО. Б.PolshvedkinaO. B.

302028

Октябрьская ул., д. 4

Орёл

302028

4, Oktyabrskaya st.

Orel

КолесниковаЮ. Г.KolesnikovaYu. G.

302028

Октябрьская ул., д. 4

302026

ул. Комсомольская д. 95

Орёл

302028

4, Oktyabrskaya st.

302026

95, Komsomolskaya st.

Orel

БУЗ Орловской области «Научно-клинический многопрофильный центр медицинской помощи матерям и детям имени З. И. Круглой»РоссияScientific and Clinical Multidisciplinary Center for Medical Aid to Mothers and Children named after Z. I. KruglaiaRussian FederationФГБОУ ВО «Орловский государственный университет имени И. С. Тургенева»РоссияOrel State University named after I. S. TurgenevRussian FederationБУЗ Орловской области «Научно-клинический многопрофильный центр медицинской помощи матерям и детям имени З. И. Круглой»; ФГБОУ ВО «Орловский государственный университет имени И. С. Тургенева»РоссияScientific and Clinical Multidisciplinary Center for Medical Aid to Mothers and Children named after Z. I. Kruglaia; Orel State University named after I. S. TurgenevRussian Federation202309042023221311Copyright © Косинова Е.И., Зубцова Т.И., Полшведкина О.Б., Колесникова Ю.Г., 20232023Косинова Е.И., Зубцова Т.И., Полшведкина О.Б., Колесникова Ю.Г.Kosinova E.I., Zubtsova Т.I., Polshvedkina O.B., Kolesnikova Y.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/2237

   Синдром Вольфа-Хиршхорна (WHS, 4p-синдром) (OMIM: 194190, МКБ-10: Q93.3) ассоциирован с частичной делецией дистальной части короткого плеча хромосомы 4 (4p16.3) и считается синдромом смежных генов. Краниофациальный фенотип пациентов включает нос в форме «шлема греческого воина», высокий лоб, выпуклую глабеллу, гипертелоризм, высокие изогнутые брови, экзофтальм, эпикант, короткий фильтр, рот с опущенным вниз уголками, микрогнатию. Данный синдром характеризуется пре- и постнатальной задержкой антропометрических показателей, врожденными пороками развития различных систем, умственной отсталостью и эпилепсией.

   Цель настоящего обзора состоит в том, чтобы представить подробные данные об этиологии, патогенезе, клинической картине синдрома, а также возможностях медицинской помощи пациентам.

   В текущем обзоре освещены важные медицинские аспекты: проблемы с питанием, характер эпилептических приступов и возможности терапии, психиатрическая помощь, особенности анестезиологического пособия.

   Wolf-Hirschhorn syndrome is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3), and is considered a contiguous gene syndrome. The craniofacial view of patients includes the «Greek warrior helmet» appeara nce of the nose, high forehead, prominent glabella, hypertelorism, highly arched eyebrows, protruding eyes, epican thal folds, short philtrum, distinct mouth with down-turned corners, micrognathia. This syndrome is characterized by pre- and postnatal delay in anthropometric parameters, congenital malformations of various systems, mental retardation and a seizure disorder.

   The purpose of this review is to provide detailed data on the etiology, pathogenesis, clinical presentation of the syndrome, as well as the possibilities of medical care for patients.

   The current review highlights important medical aspects: nutritional problems, the nature of epileptic seizures and the possibilities of therapy, psychiatric care, features of anesthesia.

синдром Вольфа-Хиршхорнаделеция 4рWHS4p-синдромWolf-Hirschhorn syndrome4p deletionWHS4p-syndromeИсследование выполнено без спонсорской поддержкиThe study was carried out without sponsorshipReferencesBattaglia A., Filippi T., Carey J. C. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. Am J Med Genet C Semin Med Genet. 2008 Nov 15; 148C(4): 246-51. doi: 10.1002/ajmg.c.30187.Battaglia A., Filippi T., Carey J. C. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. Am J Med Genet C Semin Med Genet. 2008 Nov 15; 148C(4): 246-51. doi: 10.1002/ajmg.c.30187.Mekkawy M. K., Kamel A. K., Thomas M. M., Ashaat E. A., Zaki M. S., Eid O. M., Ismail S., Hammad S. A., Megahed H., El Awady H., Refaat K. M., Hussien S., Helmy N., Abd Allah S. G., Mohamed A. M., El Ruby M. O. Clinical and genetic characterization of ten Egyptian patients with Wolf-Hirschhorn syndrome and review of literature. Mol Genet Genomic Med. 2021 Feb; 9 (2): e1546. doi: 10.1002/mgg3.1546.Mekkawy M. K., Kamel A. K., Thomas M. M., Ashaat E. A., Zaki M. S., Eid O. M., Ismail S., Hammad S. A., Megahed H., El Awady H., Refaat K. M., Hussien S., Helmy N., Abd Allah S. G., Mohamed A. M., El Ruby M. O. Clinical and genetic characterization of ten Egyptian patients with Wolf-Hirschhorn syndrome and review of literature. Mol Genet Genomic Med. 2021 Feb; 9 (2): e1546. doi: 10.1002/mgg3.1546.Zollino M., Murdolo M., Marangi G., Pecile V., Galasso C., Mazzanti L., Neri G. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet C Semin Med Genet. 2008 Nov 15; 148C(4): 257-69. doi: 10.1002/ajmg.c.30190.Zollino M., Murdolo M., Marangi G., Pecile V., Galasso C., Mazzanti L., Neri G. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet C Semin Med Genet. 2008 Nov 15; 148C(4): 257-69. doi: 10.1002/ajmg.c.30190.Sukarova-Angelovska E., Kocova M., Sabolich V., Palcevska S., Angelkova N. Phenotypic variations in wolf-hirschhorn syndrome. Balkan J Med Genet. 2014 Dec 11; 17 (1): 23-30. URL: https://pubmed.ncbi.nlm.nih.gov/25741211/.Sukarova-Angelovska E., Kocova M., Sabolich V., Palcevska S., Angelkova N. Phenotypic variations in wolf-hirschhorn syndrome. Balkan J Med Genet. 2014 Dec 11; 17 (1): 23-30. URL: https://pubmed.ncbi.nlm.nih.gov/25741211/.Malvestiti F., Benedicenti F., De Toffol S., Chinetti S., Höller A., Grimi B., Fichtel G., Braghetto M., Agrati C., Bonaparte E., Maggi F., Simoni G., Grati F. R. Recombinant chromosome 4 from a familial pericentric inversion: prenatal and adulthood wolf-hirschhorn phenotypes. Case Rep Genet. 2013; 2013: 306098. doi: 10.1155/2013/306098.Malvestiti F., Benedicenti F., De Toffol S., Chinetti S., Höller A., Grimi B., Fichtel G., Braghetto M., Agrati C., Bonaparte E., Maggi F., Simoni G., Grati F. R. Recombinant chromosome 4 from a familial pericentric inversion: prenatal and adulthood wolf-hirschhorn phenotypes. Case Rep Genet. 2013; 2013: 306098. doi: 10.1155/2013/306098.Mozer Joaquim T., Paiva Grangeiro C. H., Gaona de Oliveira Gennaro F., Galvão Gomes A., Squire J. A., Martelli L. R. Partial Monosomy 4p and Trisomy 12q due to a t(4;12)(p16.3;q24.31) Familial Translocation in Two Cousins. Mol Syndromol. 2020 Jan; 10 (5): 264-271. doi: 10.1159/000501923.Mozer Joaquim T., Paiva Grangeiro C. H., Gaona de Oliveira Gennaro F., Galvão Gomes A., Squire J. A., Martelli L. R. Partial Monosomy 4p and Trisomy 12q due to a t(4;12)(p16.3;q24.31) Familial Translocation in Two Cousins. Mol Syndromol. 2020 Jan; 10 (5): 264-271. doi: 10.1159/000501923.Chen C. P., Chern S. R., Lee C. C., Chen W. L., Chen M. H., Chang K. M. De novo unbalanced translocation resulting in monosomy for proximal 14q and distal 4p in a fetus with intrauterine growth retardation, Wolf-Hirschhorn syndrome, hypertrophic cardiomyopathy, and partial hemihypoplasia. J Med Genet. 1998 Dec; 35 (12): 1050-3. doi: 10.1136/jmg.35.12.1050.Chen C. P., Chern S. R., Lee C. C., Chen W. L., Chen M. H., Chang K. M. De novo unbalanced translocation resulting in monosomy for proximal 14q and distal 4p in a fetus with intrauterine growth retardation, Wolf-Hirschhorn syndrome, hypertrophic cardiomyopathy, and partial hemihypoplasia. J Med Genet. 1998 Dec; 35 (12): 1050-3. doi: 10.1136/jmg.35.12.1050.Kohlschmidt N., Zielinski J., Brude E., Schäfer D., Olert J., Hallermann C., Coerdt W., Arnemann J. Prenatal diagnosis of a fetus with a cryptic translocation 4p;18p and Wolf-Hirschhorn syndrome (WHS). Prenat Diagn. 2000 Feb; 20 (2): 152-5. doi: 10.1002/(sici)1097-0223(200002)20:2<152::aid-pd738>3.0.co;2-p.Kohlschmidt N., Zielinski J., Brude E., Schäfer D., Olert J., Hallermann C., Coerdt W., Arnemann J. Prenatal diagnosis of a fetus with a cryptic translocation 4p;18p and Wolf-Hirschhorn syndrome (WHS). Prenat Diagn. 2000 Feb; 20 (2): 152-5. doi: 10.1002/(sici)1097-0223(200002)20:2<152::aid-pd738>3.0.co;2-p.Xu J., Freeman V., Carter R. F., Paes B., Heshka T., Nowaczyk J. M. Wolf-Hirschorn syndrome resulting from partial monosomy 4p/tri-somy 9p. Am J Med Genet. 2000 Aug 14; 93 (4): 285-9. doi: 10.1002/1096-8628(20000814)93:4<285::aid-ajmg6>3.0.co;2-n.Xu J., Freeman V., Carter R. F., Paes B., Heshka T., Nowaczyk J. M. Wolf-Hirschorn syndrome resulting from partial monosomy 4p/tri-somy 9p. Am J Med Genet. 2000 Aug 14; 93 (4): 285-9. doi: 10.1002/1096-8628(20000814)93:4<285::aid-ajmg6>3.0.co;2-n.Tapper J. K., Zhang S., Harirah H. M., Panova N. I., Merryman L. S., Hawkins J. C., Lockhart L. H., Gei A. B., Velagaleti G. V. Prenatal diagnosis of a fetus with unbalanced translocation (4;13)(p16;q32) with overlapping features of Patau and Wolf-Hirschhorn syndromes. Fetal Diagn Ther. 2002 Nov-Dec; 17 (6): 347-51. doi: 10.1159/000065383.Tapper J. K., Zhang S., Harirah H. M., Panova N. I., Merryman L. S., Hawkins J. C., Lockhart L. H., Gei A. B., Velagaleti G. V. Prenatal diagnosis of a fetus with unbalanced translocation (4;13)(p16;q32) with overlapping features of Patau and Wolf-Hirschhorn syndromes. Fetal Diagn Ther. 2002 Nov-Dec; 17 (6): 347-51. doi: 10.1159/000065383.Šumanović-Glamuzina D., Lozić B., Iwanowski P. S., Zemunik T., Bilinovac Z., Stasiewicz-Jarocka B., Panasiuk B., Midro A. T. Limited survivability of unbalanced progeny of carriers of a unique t (4; 19) (p15.32; p13.3): a study in multiple generations. Mol Cytogenet. 2017 Aug 4;10:29. doi: 10.1186/s13039-017-0330-8.Šumanović-Glamuzina D., Lozić B., Iwanowski P. S., Zemunik T., Bilinovac Z., Stasiewicz-Jarocka B., Panasiuk B., Midro A. T. Limited survivability of unbalanced progeny of carriers of a unique t (4; 19) (p15.32; p13.3): a study in multiple generations. Mol Cytogenet. 2017 Aug 4;10:29. doi: 10.1186/s13039-017-0330-8.Beaujard M. P., Jouannic J. M., Bessières B., Borie C., Martin-Luis I. , Fallet-Bianco C, Portnoï M. F. Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype. Prenat Diagn. 2005 Jun; 25 (6): 451-5. doi: 10.1002/pd.1154.Beaujard M. P., Jouannic J. M., Bessières B., Borie C., Martin-Luis I. , Fallet-Bianco C, Portnoï M. F. Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype. Prenat Diagn. 2005 Jun; 25 (6): 451-5. doi: 10.1002/pd.1154.Ogle R., Sillence D. O., Merrick A., Ell J., Lo B., Robson L., Smith A. The Wolf-Hirschhorn syndrome in adulthood: evaluation of a 24-year-old man with a rec(4) chromosome. Am J Med Genet. 1996 Oct 16 ; 65 (2) : 12 4-7. doi: 10.1002/(SICI)1096-8628(19961016)65:2<124::AID-AJMG8>3.0.CO;2-S.Ogle R., Sillence D. O., Merrick A., Ell J., Lo B., Robson L., Smith A. The Wolf-Hirschhorn syndrome in adulthood: evaluation of a 24-year-old man with a rec(4) chromosome. Am J Med Genet. 1996 Oct 16 ; 65 (2) : 12 4-7. doi: 10.1002/(SICI)1096-8628(19961016)65:2<124::AID-AJMG8>3.0.CO;2-S.Dufke A., Eggermann K., Balg S., Stengel-Rutkowski S., Enders H. Kaiser P. A second case of inv(4)pat with both recombinants in the offspring: rec dup(4q) in a girl with Wolf-Hirschhorn syndrome and rec dup(4p). Cytogenet Cell Genet. 2000; 91 (1-4): 85-9. doi: 10.1159/000056824.Dufke A., Eggermann K., Balg S., Stengel-Rutkowski S., Enders H. Kaiser P. A second case of inv(4)pat with both recombinants in the offspring: rec dup(4q) in a girl with Wolf-Hirschhorn syndrome and rec dup(4p). Cytogenet Cell Genet. 2000; 91 (1-4): 85-9. doi: 10.1159/000056824.Mun S. J., Cho E. H., Chey M. J., Shim G. H., Shin B. M., Lee R. K., Ko J. K., Yoo S. J. [Recombinant chromosome 4 with partial 4p deletion and 4q duplication inherited from paternal pericentric inversion]. Korean J Lab Med. 2010 Feb; 30 (1): 89-92. Korean. doi: 10.3343/kjlm.2010.30.1.89.Mun S. J., Cho E. H., Chey M. J., Shim G. H., Shin B. M., Lee R. K., Ko J. K., Yoo S. J. [Recombinant chromosome 4 with partial 4p deletion and 4q duplication inherited from paternal pericentric inversion]. Korean J Lab Med. 2010 Feb; 30 (1): 89-92. Korean. doi: 10.3343/kjlm.2010.30.1.89.Paththinige C. S., Sirisena N. D., Kariyawasam U. G., Saman Kumara L. P., Dissanayake V.H. Ring Chromosome 4 in a Child with Multi-ple Congenital Abnormalities: A Case Report and Review of the Literature. Case Rep Genet. 2016; 2016: 4645716. doi: 10.1155/2016/4645716.Paththinige C. S., Sirisena N. D., Kariyawasam U. G., Saman Kumara L. P., Dissanayake V.H. Ring Chromosome 4 in a Child with Multi-ple Congenital Abnormalities: A Case Report and Review of the Literature. Case Rep Genet. 2016; 2016: 4645716. doi: 10.1155/2016/4645716.Lasser M., Pratt B., Monahan C., Kim S. W., Lowery L. A. The Many Faces of Xenopus: Xenopus laevis as a Model System to Study Wolf-Hirschhorn Syndrome. Front Physiol. 2019 Jun 26;10:817. doi: 10.3389/fphys.2019.00817.Lasser M., Pratt B., Monahan C., Kim S. W., Lowery L. A. The Many Faces of Xenopus: Xenopus laevis as a Model System to Study Wolf-Hirschhorn Syndrome. Front Physiol. 2019 Jun 26;10:817. doi: 10.3389/fphys.2019.00817.Ahmed M., Ura K., Streit A. Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome. Dis Model Mech. 2015 Sep; 8 (9): 1027-35. doi: 10.1242/dmm.019547.Ahmed M., Ura K., Streit A. Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome. Dis Model Mech. 2015 Sep; 8 (9): 1027-35. doi: 10.1242/dmm.019547.Campos-Sanchez E., Deleyto-Seldas N., Dominguez V., Carrillo-de-Santa-Pau E., Ura K., Rocha P. P., Kim J., Aljoufi A., Esteve-Codina A., Dabad M., Gut M., Heyn H., Kaneda Y., Nimura K., Skok J. A., Martinez-Frias M. L., Cobaleda C. Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development. Cell Rep. 2017 May 23; 19 (8): 1586-1601. doi: 10.1016/j.celrep.2017.04.069.Campos-Sanchez E., Deleyto-Seldas N., Dominguez V., Carrillo-de-Santa-Pau E., Ura K., Rocha P. P., Kim J., Aljoufi A., Esteve-Codina A., Dabad M., Gut M., Heyn H., Kaneda Y., Nimura K., Skok J. A., Martinez-Frias M. L., Cobaleda C. Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development. Cell Rep. 2017 May 23; 19 (8): 1586-1601. doi: 10.1016/j.celrep.2017.04.069.Barrie E. S., Alfaro M. P., Pfau R. B., Goff M. J., McBride K. L., Manickam K., Zmuda E. J. De novo loss-of-function variants in NSD2 (WHSC1) associate with a subset of Wolf-Hirschhorn syndrome. Cold Spring Harb Mol Case Stud. 2019 Aug 1; 5 (4): a004044. doi: 10.1101/mcs.a004044.Barrie E. S., Alfaro M. P., Pfau R. B., Goff M. J., McBride K. L., Manickam K., Zmuda E. J. De novo loss-of-function variants in NSD2 (WHSC1) associate with a subset of Wolf-Hirschhorn syndrome. Cold Spring Harb Mol Case Stud. 2019 Aug 1; 5 (4): a004044. doi: 10.1101/mcs.a004044.Hu X., Wu D., Li Y., Wei L., Li X., Qin M., Li H., Li M., Chen S., Gong C., Shen Y. The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy. BMC Med Genomics. 2020 Dec 4; 13 (1): 181. doi: 10.1186/s12920-020-00831-9.Hu X., Wu D., Li Y., Wei L., Li X., Qin M., Li H., Li M., Chen S., Gong C., Shen Y. The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy. BMC Med Genomics. 2020 Dec 4; 13 (1): 181. doi: 10.1186/s12920-020-00831-9.Hart L., Rauch A., Carr A. M., Vermeesch J. R., O’Driscoll M. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition. Dis Model Mech. 2014 May; 7 (5): 535-45. doi: 10.1242/dmm.014464.Hart L., Rauch A., Carr A. M., Vermeesch J. R., O’Driscoll M. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition. Dis Model Mech. 2014 May; 7 (5): 535-45. doi: 10.1242/dmm.014464.Endele S., Fuhry M., Pak S. J., Zabel B. U., Winterpacht A. LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients. Genomics. 1999 Sep 1; 60 (2): 218-25. doi: 10.1006/geno.1999.5881.Endele S., Fuhry M., Pak S. J., Zabel B. U., Winterpacht A. LETM1, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, flanks the Wolf-Hirschhorn syndrome (WHS) critical region and is deleted in most WHS patients. Genomics. 1999 Sep 1; 60 (2): 218-25. doi: 10.1006/geno.1999.5881.Antonius T., Draaisma J., Levtchenko E., Knoers N., Renier W., van Ravenswaaij C. Growth charts for Wolf-Hirschhorn syndrome (0-4 years of age). Eur J Pediatr. 2008 Jul; 167 (7): 807-10. doi: 10.1007/s00431-007-0595-8.Antonius T., Draaisma J., Levtchenko E., Knoers N., Renier W., van Ravenswaaij C. Growth charts for Wolf-Hirschhorn syndrome (0-4 years of age). Eur J Pediatr. 2008 Jul; 167 (7): 807-10. doi: 10.1007/s00431-007-0595-8.Austin D. E., Gunn A. J.., Jefferies C. A. Severe short stature and Wolf-Hirschhorn syndrome: response to growth hormone in two cases without growth hormone deficiency. Oxf Med Case Reports. 2015 Feb 28; 2015 (2): 211-4. doi: 10.1093/omcr/omv008.Austin D. E., Gunn A. J.., Jefferies C. A. Severe short stature and Wolf-Hirschhorn syndrome: response to growth hormone in two cases without growth hormone deficiency. Oxf Med Case Reports. 2015 Feb 28; 2015 (2): 211-4. doi: 10.1093/omcr/omv008.Ali M. H., Azar N. F., Aakalu V., Chau F. Y., Abbasian J., Setabutr P., Maumenee I. H. Congenital cavitary optic disc anomaly and Axenfeld’s anomaly in Wolf-Hirschhorn syndrome: A case report and review of the literature. Ophthalmic Genet. 2018 Apr; 39 (2): 271-274. doi: 10.1080/13816810.2017.1408850.Ali M. H., Azar N. F., Aakalu V., Chau F. Y., Abbasian J., Setabutr P., Maumenee I. H. Congenital cavitary optic disc anomaly and Axenfeld’s anomaly in Wolf-Hirschhorn syndrome: A case report and review of the literature. Ophthalmic Genet. 2018 Apr; 39 (2): 271-274. doi: 10.1080/13816810.2017.1408850.Limeres J., Serrano C., De Nova J. M., Silvestre-Rangil J., Machuca G., Maura I., Cruz Ruiz-Villandiego J., Diz P., Blanco-Lago R., Nevado J., Diniz-Freitas M. Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis. J Clin Med. 2020 Nov 4; 9 (11): 3556. doi: 10.3390/jcm9113556.Limeres J., Serrano C., De Nova J. M., Silvestre-Rangil J., Machuca G., Maura I., Cruz Ruiz-Villandiego J., Diz P., Blanco-Lago R., Nevado J., Diniz-Freitas M. Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis. J Clin Med. 2020 Nov 4; 9 (11): 3556. doi: 10.3390/jcm9113556.Hong Y. M., Cho D. H., Kim J. K. Nonossified cervical vertebrae in Wolf-Hirschhorn Syndrome: A case report. Medicine (Baltimore). 2019 Dec; 98 (50): e18268. doi: 10.1097/MD.0000000000018268.Hong Y. M., Cho D. H., Kim J. K. Nonossified cervical vertebrae in Wolf-Hirschhorn Syndrome: A case report. Medicine (Baltimore). 2019 Dec; 98 (50): e18268. doi: 10.1097/MD.0000000000018268.Heljić S., Catibusić F., Dozić M., Mackić M. Wolf-Hirschhornov sindrom [Wolf-Hirschhorn syndrome]. Med Arh. 2004; 58 (5): 318-20. [In Bosnian].Heljić S., Catibusić F., Dozić M., Mackić M. Wolf-Hirschhornov sindrom [Wolf-Hirschhorn syndrome]. Med Arh. 2004; 58 (5): 318-20. [In Bosnian].Percell R. L. Jr., Percell H. C., Miller K. A. A Different Breed of Wolf: First Known Case of Wolf-Hirschorn Syndrome with Third-degree Atrioventricular Block Requiring Pacemaker Implantation. J Innov Card Rhythm Manag. 2020 Jun 15; 11 (6): 4147-4150. doi: 10.19102/icrm.2020.110601.Percell R. L. Jr., Percell H. C., Miller K. A. A Different Breed of Wolf: First Known Case of Wolf-Hirschorn Syndrome with Third-degree Atrioventricular Block Requiring Pacemaker Implantation. J Innov Card Rhythm Manag. 2020 Jun 15; 11 (6): 4147-4150. doi: 10.19102/icrm.2020.110601.Deeb A. Diabetes Mellitus Secondary to Acute Pancreatitis in a Child with Wolf-Hirschhorn Syndrome. Case Rep Endocrinol. 2017; 2017: 3892467. doi: 10.1155/2017/3892467.Deeb A. Diabetes Mellitus Secondary to Acute Pancreatitis in a Child with Wolf-Hirschhorn Syndrome. Case Rep Endocrinol. 2017; 2017: 3892467. doi: 10.1155/2017/3892467.Hanley-Lopez J., Estabrooks L. L., Stiehm R. Antibody deficiency in Wolf-Hirschhorn syndrome. J Pediatr. 1998 Jul; 133 (1): 141-3. doi: 10.1016/s0022-3476(98)70194-5.Hanley-Lopez J., Estabrooks L. L., Stiehm R. Antibody deficiency in Wolf-Hirschhorn syndrome. J Pediatr. 1998 Jul; 133 (1): 141-3. doi: 10.1016/s0022-3476(98)70194-5.Zorron R., Cunha S. H., Barreto M. C., Phillips H. N. Single port laparoscopic splenectomy for wandering spleen with splenomegaly in a patient with Wolf-Hirschhorn syndrome. J Minim Access Surg. 2017 Apr-Jun; 13 (2): 135-138. doi: 10.4103/0972-9941.195567.Zorron R., Cunha S. H., Barreto M. C., Phillips H. N. Single port laparoscopic splenectomy for wandering spleen with splenomegaly in a patient with Wolf-Hirschhorn syndrome. J Minim Access Surg. 2017 Apr-Jun; 13 (2): 135-138. doi: 10.4103/0972-9941.195567.Sharathkumar A., Kirby M., Freedman M., Abdelhaleem M., Chitayat D., Teshima I. E., Dror Y. Malignant hematological disorders in children with Wolf-Hirschhorn syndrome. Am J Med Genet A. 2003 Jun 1; 119A(2):194-9. doi: 10.1002/ajmg.a.20080.Sharathkumar A., Kirby M., Freedman M., Abdelhaleem M., Chitayat D., Teshima I. E., Dror Y. Malignant hematological disorders in children with Wolf-Hirschhorn syndrome. Am J Med Genet A. 2003 Jun 1; 119A(2):194-9. doi: 10.1002/ajmg.a.20080.Batton B., Amanullah A., Main C., Fivenson D., Jamil S. Cutaneous T-cell lymphoma in a 21-year-old male with Wolf-Hirschhorn syndrome. Am J Med Genet A. 2004 May 15; 127A(1):81-5. doi: 10.1002/ajmg.a.20608.Batton B., Amanullah A., Main C., Fivenson D., Jamil S. Cutaneous T-cell lymphoma in a 21-year-old male with Wolf-Hirschhorn syndrome. Am J Med Genet A. 2004 May 15; 127A(1):81-5. doi: 10.1002/ajmg.a.20608.Marte A., Indolfi P., Ficociello C., Russo D., Oreste M., Bottigliero G., Gualdiero G., Barone C., Vigliar E., Indolfi C., Casale F. Inflammatory myofibroblastic bladder tumor in a patient with wolf-hirschhorn syndrome. Case Rep Urol. 2013; 2013: 675059. doi: 10.1155/2013/675059.Marte A., Indolfi P., Ficociello C., Russo D., Oreste M., Bottigliero G., Gualdiero G., Barone C., Vigliar E., Indolfi C., Casale F. Inflammatory myofibroblastic bladder tumor in a patient with wolf-hirschhorn syndrome. Case Rep Urol. 2013; 2013: 675059. doi: 10.1155/2013/675059.Go H., Haneda K., Maeda H., Ogasawara K., Imamura T., Momoi N., Hosoya M. Early Postnatal Seizures in a Neonate with Wolf-Hirschhorn Syndrome. AJP Rep. 2016 Oct; 6 (4): e427-e429. doi: 10.1055/s-0036-1597580.Go H., Haneda K., Maeda H., Ogasawara K., Imamura T., Momoi N., Hosoya M. Early Postnatal Seizures in a Neonate with Wolf-Hirschhorn Syndrome. AJP Rep. 2016 Oct; 6 (4): e427-e429. doi: 10.1055/s-0036-1597580.Battaglia D., Zampino G., Zollino M., Mariotti P., Acquafondata C., Lettori D., Pane M., Vasta I., Neri G., Dravet C., Guzzetta F. Electroclinical patterns and evolution of epilepsy in the 4p- syndrome. Epilepsia. 2003 Sep; 44 (9): 1183-90. doi: 10.1046/j.1528-1157.2003.63502.x.Battaglia D., Zampino G., Zollino M., Mariotti P., Acquafondata C., Lettori D., Pane M., Vasta I., Neri G., Dravet C., Guzzetta F. Electroclinical patterns and evolution of epilepsy in the 4p- syndrome. Epilepsia. 2003 Sep; 44 (9): 1183-90. doi: 10.1046/j.1528-1157.2003.63502.x.Motoi H., Okanishi T., Kanai S., Yokota T., Yamazoe T., Nishimura M., Fujimoto A., Yamamoto T., Enoki H. Wolf-Hirschhorn (4p-) syndrome with West syndrome. Epilepsy Behav Case Rep. 2016 Jul 15; 6: 39-41. doi: 10.1016/j.ebcr.2016.07.001.Motoi H., Okanishi T., Kanai S., Yokota T., Yamazoe T., Nishimura M., Fujimoto A., Yamamoto T., Enoki H. Wolf-Hirschhorn (4p-) syndrome with West syndrome. Epilepsy Behav Case Rep. 2016 Jul 15; 6: 39-41. doi: 10.1016/j.ebcr.2016.07.001.Kim H. J., You J. A., Park S., Kim E. J., Park S. J., Kim H. Y. Anesthetic considerations for an adult with Wolf-Hirschhorn syndrome - A case report. Anesth Pain Med (Seoul). 2020 Jan 31; 15 (1): 120-123. doi: 10.17085/apm.2020.15.1.120.Kim H. J., You J. A., Park S., Kim E. J., Park S. J., Kim H. Y. Anesthetic considerations for an adult with Wolf-Hirschhorn syndrome - A case report. Anesth Pain Med (Seoul). 2020 Jan 31; 15 (1): 120-123. doi: 10.17085/apm.2020.15.1.120.Choi J. H., Kim J. H., Park Y. C., Kim W. Y., Lee Y. S. Anesthetic experience using total intra-venous anesthesia for a patient with Wolf-Hirschhorn syndrome -A case report-. Korean J Anesthesiol. 2011 Feb; 60 (2): 119-23. doi: 10.4097/kjae.2011.60.2.119.Choi J. H., Kim J. H., Park Y. C., Kim W. Y., Lee Y. S. Anesthetic experience using total intra-venous anesthesia for a patient with Wolf-Hirschhorn syndrome -A case report-. Korean J Anesthesiol. 2011 Feb; 60 (2): 119-23. doi: 10.4097/kjae.2011.60.2.119.Xing Y., Holder J. L. Jr., Liu Y., Yuan M., Sun Q., Qu X., Deng L., Zhou J., Yang Y., Guo M., Cheung S. W., Sun L. Prenatal diagnosis of Wolf-Hirschhorn syndrome: from ultrasound findings, diagnostic technology to genetic counseling. Arch Gynecol Obstet. 2018 Aug; 298 (2): 289-295. doi: 10.1007/s00404-018-4798-1.Xing Y., Holder J. L. Jr., Liu Y., Yuan M., Sun Q., Qu X., Deng L., Zhou J., Yang Y., Guo M., Cheung S. W., Sun L. Prenatal diagnosis of Wolf-Hirschhorn syndrome: from ultrasound findings, diagnostic technology to genetic counseling. Arch Gynecol Obstet. 2018 Aug; 298 (2): 289-295. doi: 10.1007/s00404-018-4798-1.

The authors declare that there are no conflicts of interest present.