BACKGROUND: Ring 18 chromosome is a rare chromosomal aberration associated with a wide range of symptoms affecting all organ systems. One possible symptom associated with this condition is an orofacial cleft. However, to date, there are very few reported cases where the cleft has been surgically treated. CASE DESCRIPTION: In our case study, we present a female patient with Ring 18 chromosome who underwent cleft palate surgery at 14 months of age. Subsequently, a reoperation of the palate was necessary due to wound dehiscence. For the secondary reconstruction of the palate, the acellular dermal matrix (ADM) MatriDerm® was used to improve healing. The cleft palate surgery progressively improved her ability to take in food, allowing a transition from nasogastric tube feeding to oral intake. RESULTS: This is only the fourth reported case of a child with Ring 18 chromosome undergoing surgical correction of an orofacial cleft. Additionally, it is one of the first cases where an ADM MatriDerm® was used in the surgical correction of a cleft palate. In this study, we also present a comprehensive literature review, providing an overview of the various symptoms associated with this syndrome. CONCLUSION: Cleft palate surgery had a very positive effect on improving food intake in the patient with Ring 18 chromosome. The use of an acellular dermal matrix during the secondary cleft palate surgery led to improved healing and a good outcome.

Department of Burns and Plastic Surgery University Hospital Brno Jihlavska 20 Brno 62500 Czech Republic

Department of Pediatric Anesthesiology and Intensive Care University Hospital Brno Brno Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

See more in PubMed

Kosztolányi G. The genetics and clinical characteristics of constitutional ring chromosomes. J Assoc Genet Technol. 2009;35(2):44–8. PubMed

Li P, et al. The past, present, and future for constitutional ring chromosomes: A report of the international consortium for human ring chromosomes. HGG Adv. Oct. 2022;3(4):100139. 10.1016/j.xhgg.2022.100139. PubMed PMC

Kosztolányi G, Méhes K, Hook EB. ‘Inherited ring chromosomes: an analysis of published cases’, Hum Genet. Jul. 1991;87(3):320–324. 10.1007/BF00200912 PubMed

Cody JD, et al. Preferential loss of the paternal alleles in the 18q- syndrome. Am J Med Genet. Mar. 1997;69(3):280–6. 10.1002/(sici)1096-8628(19970331)69:3%3C280::aid-ajmg12%3E3.0.co;2-n. PubMed

Kalker U, Gabriel M, Jacobi G. ‘Van der Woude syndrome in combination with ring chromosome 18’, Monatsschr Kinderheilkd. Feb. 1998;136(2):95–98. PubMed

Tavin E, Stecker E, Marion R. Nasal pyriform aperture stenosis and the holoprosencephaly spectrum. Int J Pediatr Otorhinolaryngol. Jan. 1994;28:2–3. 10.1016/0165-5876(94)90012-4. PubMed

Thomas JV et al. ‘Growth hormone deficiency, hypothyroidism and ring chromosome 18: case report’, Arq Bras Endocrinol Metabol. Oct. 2006;50(5):951–956. 10.1590/s0004-27302006000500019 PubMed

Souraty N, et al. Cytogenetic investigation of a child with a mosaic isochromosome 18q and ring 18q. Eur J Med Genet. 2007;50(5):379–85. 10.1016/j.ejmg.2007.06.001. PubMed

Chen C-P et al. Sep., ‘Mosaic ring chromosome 18, ring chromosome 18 duplication/deletion and disomy 18: perinatal findings and molecular cytogenetic characterization by fluorescence in situ hybridization and array comparative genomic hybridization’, Taiwan J Obstet Gynecol. 2010;49(3):327–332. 10.1016/S1028-4559(10)60069-1 PubMed

Dobos M et al. ‘Ring Chromosome 18: Clinical, Cytogenetic and Molecular Genetic Studies on Four Patients’, International Journal of Human Genetics. Sep. 2004;4(3):197–200. 10.1080/09723757.2004.11885892

Chau A, Ramesh KH, Jagannath AD, Arora S. ‘Rheumatoid arthritis in an adult patient with mosaic distal 18q-, 18p- and ring chromosome 18’, F1000Res. 2017;6:1940. 10.12688/f1000research.11539.2 PubMed PMC

Vazna A, Havlovicova M, Sedlacek Z. ‘Molecular cloning and analysis of breakpoints on ring chromosome 17 in a patient with autism’, Gene. Jan. 2008;407(1–2):186–192. 10.1016/j.gene.2007.10.009 PubMed

McGinniss MJ et al. Jan., ‘Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21’, Am J Hum Genet. 1992;50(1):15–28. PubMed PMC

Daber RD, et al. Ring chromosome 20. Eur J Med Genet. May 2012;55(5):381–7. 10.1016/j.ejmg.2012.02.004. PubMed

Conlin LK, et al. Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients. J Med Genet. Jan. 2011;48(1):1–9. 10.1136/jmg.2010.080382. PubMed

Stankiewicz P, et al. Clinical and molecular-cytogenetic studies in seven patients with ring chromosome 18. Am J Med Genet. Jul. 2001;101(3):226–39. 10.1002/1096-8628(20010701)101:3%3C226::aid-ajmg1349%3E3.0.co;2-#. PubMed

Wang H-C, Melnyk J, Mcdonald LT, Uchida IA, Carr DH, Goldberg B. ‘Ring Chromosomes in Human Beings’, Nature. Aug. 1962;195(4842):733–734. 10.1038/195733a0 PubMed

Koç A et al. Jun., ‘An unexpected finding in a child with neurological problems: mosaic ring chromosome 18’, Eur J Pediatr. 2008;167(6):655–659. 10.1007/s00431-007-0568-y PubMed

Carter E, et al. Ring 18 molecular assessment and clinical consequences. Am J Med Genet A. Jan. 2015;167A(1):54–63. 10.1002/ajmg.a.36822. PubMed

Schinzel A. Catalogue of Unbalanced Chromosome Aberrations in Man. De Gruyter; 2020. 10.1515/9783112329047.

Miller K et al. Apr., ‘Chromosome 18 replaced by two ring chromosomes of chromosome 18 origin’, Hum Genet. 2003;112(4):343–347. 10.1007/s00439-002-0885-1 PubMed

Litzman J, et al. Agammaglobulinaemia in a girl with a mosaic of ring 18 chromosome. J Paediatr Child Health. Feb. 1998;34(1):92–4. 10.1046/j.1440-1754.1998.00162.x. PubMed

Rezaeizadeh T, Delshad E, Samaei NM, Gholipour N. ‘A case report of Ring chromosome 18 with systemic Lupus Erythematosus and Crohn’s disease’. Mol Biol Rep. Feb. 2002;49(2):1085–1088. 10.1007/s11033-021-06933-6 PubMed

Heydari S, Hassanzadeh F, Hassanzadeh Nazarabadi M. Ring chromosome 18: a case report. Int J Mol Cell Med. 2014;3(4):287–9. PubMed PMC

Wang J, Xiao L, Wang J, Ding Z, Ni J, Long X. ‘Mosaic ring chromosome 18 in a Chinese child with epilepsy: a case report and review of the literature’, Neurol Sci. Dec. 2021;42(12):5231–5239. 10.1007/s10072-021-05143-z PubMed

Jain N, Reitnauer PJ, Rao KW, Aylsworth AS, Calikoglu AS. Autoimmune polyendocrinopathy associated with ring chromosome 18. J Pediatr Endocrinol Metab. 2011;24:9–10. 10.1515/jpem.2011.320. PubMed

Celep F, Sonmez FM, Kul S, Ucar F, Karaguzel A. ‘Ring chromosome 18 in a child with febrile seizures’, Genet Couns. 2011;22(2):165–171. PubMed

Lyu Y et al. ‘[Molecular cytogenetic diagnosis of a case with ring chromosome 18 syndrome]’, Zhonghua Yi Xue Yi Chuan Xue Za Zhi. Oct. 2019;36(10):1010–1014. 10.3760/cma.j.issn.1003-9406.2019.10.015 PubMed

Dacou-Voutetakis C, et al. Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18. J Med Genet. 1999;36(2):156–8. PubMed PMC

Amit R, Gutman A, Udassin R, Barash V, Kohn G. Ring 18 chromosome with mental retardation, hemidysmorphism, and mitochondrial encephalomyopathy. Pediatr Neurol. 1988;4(5):301–4. 10.1016/0887-8994(88)90070-7. PubMed

Celmeli F, Turkkahraman D, Cetin Z, Mihci E, Yegin O. Selective IgM deficiency in a boy with ring chromosome 18. J Investig Allergol Clin Immunol. 2014;24(6):442–4. PubMed

Winter JS, Ahluwalia K, Ray M. ‘Conenital hypothyroidism in association with a ring chromosome 18’, J Med Genet. Mar. 1972;9(1):122–126. 10.1136/jmg.9.1.122 PubMed PMC

Takenouchi T, et al. Tissue-limited ring chromosome 18 mosaicism as a cause of Pitt–Hopkins syndrome. Am J Med Genet Part A. 2012;158A(10):2621–3. 10.1002/ajmg.a.35230. PubMed

Zlotina A et al. Feb., ‘Ring chromosome 18 in combination with 18q12.1 (DTNA) interstitial microdeletion in a patient with multiple congenital defects’, Molecular Cytogenetics (17558166). 2016;9:1–7. 10.1186/s13039-016-0229-9 PubMed PMC

Varas-Meis E, Delgado-Vicente S, Fernández-Canga P, Prieto MÁR. Blaschkoid hypermelanosis in a patient with ring 18 chromosome. Indian J Dermatol Venereol Leprol. May 2020;86:316. 10.4103/ijdvl.IJDVL_282_18. PubMed

Yao H, et al. Breakpoints and deleted genes identification of ring chromosome 18 in a Chinese girl by whole-genome low-coverage sequencing: a case report study. BMC Med Genet. Jul. 2016;17:49. 10.1186/s12881-016-0307-1. PubMed PMC

Mello AL et al. Sep., ‘Clinical course of a 20-month-old child diagnosed prenatally with mosaic ring chromosome 18 and monosomy 18.’. South Dakota medicine: the journal of the South Dakota State Medical Association. 2008;61(9):327. PubMed

Samli H, et al. A case with mosaic ring chromosome 18. Gazi Med J. 2013;24(3). 10.12996/gmj.2013.26.

Yeganeh M, et al. Primary antibody deficiency associated with ring chromosome 18. LynphoSign J. Mar. 2020;7(1):25–36. 10.14785/lymphosign-2019-0013.

Lammert DB et al. ‘Central and peripheral dysmyelination in a 3-year‐old girl with ring chromosome 18’. Clinical Case Reports. Sep. 2019;7(11):2087. 10.1002/ccr3.2426 PubMed PMC

Michaels DL, Go S, Humbert JR, Dubois RS, Stewart JM, Ellis EF. ‘Intestinal nodular lymphoid hyperplasia, hypogammaglobulinemia, and hematologic abnormalities in a child with a ring 18 chromosome’. J Pediatrics. Jul. 1971;79(1):80–88. 10.1016/S0022-3476(71)80062-8 PubMed

Kadotani T, Watanabe Y. ‘A case with ring chromosome of No. 18.’. Proc Jpn Acad Ser B. 1984;60(9):372–373. 10.2183/pjab.60.372

Fryns JP, Kleczkowska A. Autism and ring chromosome 18 mosaicism. Clin Genet. Jul. 1992;42(1):55. 10.1111/j.1399-0004.1992.tb03139.x. PubMed

Lo-Castro A, et al. De novo mosaic ring chromosome 18 in a child with mental retardation, epilepsy and immunological problems. Eur J Med Genet vol. May 2011;54(3):329–32. 10.1016/j.ejmg.2011.02.004. PubMed

Bagherizadeh E, Behjati F, Saberi SH, Shafeghati Y. ‘Prenatal diagnosis in a mentally retarded woman with mosaic ring chromosome 18’. Indian J Human Genetics. Aug. 2011;17(2):111. 10.4103/0971-6866.86201 PubMed PMC

Benini R, Saint-Martin C, Shevell MI, Bernard G. ‘Abnormal Myelination in Ring Chromosome 18 Syndrome’. J Child Neurol. Aug. 2012;27(8):1042–1047. 10.1177/0883073811430268 PubMed

Nakayama J et al. Dec., ‘Abnormal myelination in a patient with ring chromosome 18’. Neuropediatrics. 1997;28(6):335–337. 10.1055/s-2007-973727 PubMed

Jensen K, Christensen KR, Jacobsen P, Nielsen J, Friedrich U, Tsuboi T. ‘Ring chromosome 18 and gamma-M-globulin abnormality’. Lancet. Aug. 1969;2(7618):497–498. 10.1016/s0140-6736(69)90206-2 PubMed

Ohkubo K, Ihara K, Ohga S, Ishimura M, Hara T. ‘Hypothyroidism and levothyroxine-responsive liver dysfunction in a patient with ring chromosome 18 syndrome’. Thyroid. Oct. 2012;22(10):1080–1083. 10.1089/thy.2011.0521 PubMed PMC

Sripanidkulchai R, Suphakunpinyo C, Jetsrisuparb C, Luengwattanawanich S. ‘Thai girl with ring chromosome 18 (46XX, r18).’. J Med Associat Thailand = Chotmaihet thangphaet. Jun. 2006;89(6):878–881. PubMed

Benito E et al. ‘Ring chromosome 18 46,XY,r(18)’. An Esp Pediatr. Feb. 1987;26(2):121–123. PubMed

Eras N. ‘A Case of Ring Chromosome 18 with Single Umbilical Artery Detected During Prenatal Period’. Molecul Syndromol. Nov. 2020;11(4):217–222. 10.1159/000509646 PubMed PMC

Jenderny J, Caliebe A, Beyer C, Grote W. Transmission of a ring chromosome 18 from a mother with 46,XX/47,XX, + r(18) mosaicism to her daughter, resulting in a 46,XX,r(18) karyotype. J Med Genet. Nov. 1993;30(11):964. 10.1136/jmg.30.11.964. PubMed PMC

Kagimoto Y, Mizuashi M, Kikuchi K, Aiba S. ‘A case of ophiasis type of alopecia areata in a patient with ring chromosome 18 syndrome’. J Dermatol. Jun. 2014;41(6):559–560. 10.1111/1346-8138.12512 PubMed

Anzai M, et al. Patchy white matter hyperintensity in ring chromosome 18 syndrome. Pediatr Int. 2016;58(9):919–22. 10.1111/ped.13043. PubMed

Los FJ, van den Berg C, Braat APG, Cha’ban FK, Kros JM, Opstal DV. Ring chromosome 18 in a fetus with only facial anomalies. Am J Med Genet. 1996;66(2):216–20. 10.1002/(SICI)1096-8628(19961211)66:2%3C216::AID-AJMG18%3E3.0.CO;2-W. PubMed

Ono T, Okuma M, Hamada T, Motohashi N, Moriyama K. ‘A case of ring chromosome 18 syndrome treated with a combined orthodontic-prosthodontic approach’. Cleft Palate Craniofac J. Mar. 2010;47(2):201–210. 10.1597/08-262_1 PubMed

van der Veken LT, et al. Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with multiple congenital anomalies. Mol Cytogenet. Jul. 2010;3:13. 10.1186/1755-8166-3-13. PubMed PMC

Abusrewil SS, McDermott A, Savage DC. ‘Growth hormone, suspected gonadotrophin deficiency, and ring 18 chromosome’. Arch Dis Child. Sep. 1988;63(9):1090–1091. 10.1136/adc.63.9.1090 PubMed PMC

Meloni A, Boccone L, Angius L, Loche S, Falchi AM, Cao A. ‘Hypothalamic growth hormone deficiency in a patient with ring chromosome 18’. Eur J Pediatr. Feb. 1994;153(2):110–112. 10.1007/BF01959220 PubMed

Aritaki S, Takagi A, Someya H, Jun L. ‘Growth hormone neurosecretory dysfunction associated with ring chromosome 18’. Pediatrics International. 1996;38(5):544–548. 10.1111/j.1442-200X.1996.tb03543.x PubMed

Olambiwonnu NO, Ebbin AJ, Frasier SD. Primary hypoparathyroidism associated with ring chromosome 18. J Pediatr. May 1972;80(5):833–5. 10.1016/s0022-3476(72)80140-9. PubMed

Golinko MS, Mason K, Nett K, Riski JE, Williams JK. Sphincterplasty for Velopharyngeal Insufficiency in the Child Without a Cleft-Palate: Etiologies and Speech Outcomes. J Craniofac Surg. Oct. 2015;26(7):2067–71. 10.1097/SCS.0000000000001967. PubMed

Simpson A, Samargandi OA, Wong A, Graham ME, Bezuhly M. ‘Repair of Primary Cleft Palate and Oronasal Fistula With Acellular Dermal Matrix: A Systematic Review and Surgeon Survey’. Cleft Palate Craniofac J. Feb. 2019;56(2):187–195. 10.1177/1055665618774028 PubMed

Alonso V, Abuin AS-, Duran C, Gomez O, Miguez L, Molina ME. Three-layered repair with a collagen membrane and a mucosal rotational flap reinforced with fibrine for palatal fistula closure in children. Int J Pediatr Otorhinolaryngol. Dec. 2019;127:109679. 10.1016/j.ijporl.2019.109679. PubMed

Clark JM, Saffold SH, Israel JM. ‘Decellularized dermal grafting in cleft palate repair’. Arch Facial Plast Surg. 2003;5(1):40–4; discussion 45. 10.1001/archfaci.5.1.40 PubMed

Gilardino MS, Aldekhayel S, Govshievich A. ‘A Prospective Study Investigating Fistula Rate Following Primary Palatoplasty Using Acellular Dermal Matrix’. Plast Reconstr Surg Glob Open. Jun. 2018;6(6,):e1826. 10.1097/GOX.0000000000001826 PubMed PMC

Goh BKL, Chia H-L. ‘The Use of Acellular Dermal Matrix in Combination With Pedicled Buccal Fat Pad in Wide Cleft Palate Repair: A Case Report and Literature Review’. Cleft Palate Craniofac J. Nov. 2019;56(10):1381–1385. 10.1177/1055665619851915 PubMed

Ha JH, Jeong Y, Koo YT, Jeon S, Chung J, Kim S. Effect of collagen matrix on postoperative palatal fistula in cleft palate repair. Sci Rep. Sep. 2020;10(1):15236. 10.1038/s41598-020-72046-y. PubMed PMC

Emodi O et al. ‘Cleft Palate Fistula Closure Utilizing Acellular Dermal Matrix’. Plast Reconstr Surg Glob Open. Mar. 2018;6(3):e1682. 10.1097/GOX.0000000000001682 PubMed PMC