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Ring Chromosome 4

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Human Ring Chromosomes

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Abstract

We describe the cytogenomic and clinical characteristics of 47 individuals of ring chromosome 4 (RC4) published in the literature. In nine cases, mosaicism for a normal cell line was observed, but no other forms of constitutional mosaicism involving different stable anomalies of chromosome 4 were reported. All published RC4 were large with distal breakpoints most often in p15-p16 and q34-q35. Given the variability of genomic imbalance related to the different sizes of RC4, there is clinical variability. Individuals with a near complete RC4 often present with normal neurodevelopment, but demonstrate poor growth likely related to the “ring syndrome”. Patients with larger deletions that encompass the 4p Wolf–Hirschhorn critical region present with features of this syndrome. Those with a larger 4q deletion present with variable anomalies. Of note, none of these cases have the characteristic features of the 4q deletion syndrome since the majority had breakpoints that were distal to the typical 4q31-q35 region. Based on this review, it is recommended to obtain imaging for heart and renal anomalies, as well as assessment of vision, hearing, and neurodevelopment. Genetic counseling for the possibility of gonadal mosaicism is also recommended as recurrence in a family has been reported.

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References

  • Akbas H, Cine N, Erdemoglu M, Atay AE, Simsek S, Turkyilmaz A, Fidanboy M (2013) Prenatal diagnosis of 4p and 4q subtelomeric microdeletion in de novo ring chromosome 4. Case Rep Obstet Gynecol 2013(1):1–5. https://doi.org/10.1155/2013/248050

  • Anderson CE, Wallerstein R, Zamerowski ST, Witzleben C, Hoyer JR, Gibas L, Jackson LG (1997) Ring chromosome 4 mosaicism coincidence of oligomeganephronia and signs of Seckel syndrome. Am J Med Genet 72(3):281–285. https://doi.org/10.1002/(sici)1096-8628(19971031)72:33.0.co;2-u

  • Balcı S, Engiz Ö, Aktaş D, Vargel I, Beksaç MS, Mrasek K, Vermeesch J, Liehr T (2006) Ring chromosome 4 and Wolf-Hirschhorn syndrome (WHS) in a child with multiple anomalies. Am J Med Genet 140A(6):628–632. https://doi.org/10.1002/ajmg.a.31131

  • Bartram CR (1977) Sister chromatid exchanges in a ring chromosome 4. Cytogenet Genome Res 18(4):238–241. https://doi.org/10.1159/000130766

  • Blackett PR, Li S, Mulvihill JJ (2005) Ring chromosome 4 in a patient with early onset type 2 diabetes, deafness, and developmental delay. Am J Med Genet 137A(2):213–216. https://doi.org/10.1002/ajmg.a.20386

  • Burgemeister AL, Daumiller E, Dietze-Armana I, Klett C, Freiberg C, Stark W, Lingen M, Centonze I, Rettenberger G, Mehnert K (2017) Continuing role for classical cytogenetics: Case report of a boy with ring syndrome caused by complete ring chromosome 4 and review of literature. Am J Med Genet 173(3):727–732. https://doi.org/10.1002/ajmg.a.38063

  • Bobrow M, Joness LF, Clarke G (1971) A complex chromosomal rearrangement with formation of a ring 4. J Med Genet 8(2):235–239. https://doi.org/10.1136/jmg.8.2.235

  • Bofinger MK (1973) Reduction malformations and chromosome anomalies. Arch Pediatr Adolesc Med 125(1):135–143. https://doi.org/10.1001/archpedi.1973.04160010095024

  • Calabrese G, Giannotti A, Mingarelli R, Di Gilio MC, Piemontese MR, Palka G (1997) Case Report: Two newborns with chromosome 4 imbalances: Deletion 4q33 → q35 and ring r (4) (pterq35.2-qter). Clin Gen 51(4):264–267. https://doi.org/10.1111/j.1399-0004.1997.tb02467.x

  • Carter R, Baker E, Hayman D (1969) Congenital malformations associated with a ring 4 chromosome. J Med Genet 6(2):224–227. https://doi.org/10.1136/jmg.6.2.224

  • Chavin-Colin F, Turleau C, Limal JM, de Grouchy J (1977) Anneau du chromosome 4 II.—Sans dysmorphie faciale [Ring of the chromosome 4. II. Without facial dysmorphism]. Ann Genet 20(2):105–109

    Google Scholar 

  • Chen CP, Hsu CY, Tzen CY, Lee CC, Chen WL, Chen LF, Wang W (2007) Prenatal diagnosis of mosaic ring chromosome 4. Prenat Diagn 27(5):485–487. https://doi.org/10.1002/pd.1717

  • Chen CP, Lin SP, Su YN, Chern SR, Tsai EJ, Wu PC, Lee CC, Wang W (2011) Mosaic ring chromosome 4 in a child with mild dysmorphisms, congenital heart defects and developmental delay. Genet Couns 22(3):321–326

    Google Scholar 

  • Concolino D, Rossi E, Strisciuglio P, Iembo MA, Giorda R, Ciccone R, Tenconi R, Zuffardi O (2007) Deletion of a 760 kb region at 4p16 determines the prenatal and postnatal growth retardation characteristic of Wolf-Hirschhorn syndrome. J Med Genet 44(10):647–650. https://doi.org/10.1136/jmg.2007.050963

  • del Mazo J, Abrisqueta JA, Pérez-Castillo A, Aller V, Lucas MAM, de Torres ML, Martín MJ (1978) Partial deletion of 4p16 band in a ring chromosome and Wolf syndrome. Hum Genet 44(1):105–108. https://doi.org/10.1007/BF00283580

  • Dominguez MG, Barros-Núñez P, González-Ramos IA, Rivera H (2010) Variegated-like mosaicism and ring syndrome in a r(4) boy. Appraisal of 38 patients with a fairly complete ring 4. Genet Couns 21(4):411–422

    Google Scholar 

  • Finley WH, Finley S, Chonmaitree T, Koors J, Chandler W (1981) Ring 4 chromosome with terminal p and q deletions. Arch Pediatr Adolesc Med 135(8):729-731. https://doi.org/10.1001/archpedi.1981.02130320043015

  • Fraisse J, Lauras B, Couturier J, Freycon F (1977) Ring of the chromosome 4. I – with 4p- phenotype. Ann Genet 20(2):101–104

    Google Scholar 

  • Freyberger G, Wamsler C, Schmid M (1991) Ring chromosome 4 in a child with mild dysmorphic signs. 39(2):151–155. https://doi.org/10.1111/j.1399-0004.1991.tb03003.x

  • Fryns JP, Kleczkowska A, Jaeken J, Van den Berghe H (1988) Ring chromosome 4 mosaicism and Potter sequence. Ann Genet 31(2):120–122

    Google Scholar 

  • Giuffrè L, Cammarata M, Corsello G, Benigno V, Graziano L, Roccella F, Balsamo V (1987) [Ring chromosome 4 in twins] Pediatr Med Chir 9(3):349–350

    Google Scholar 

  • Guilherme RS, Meloni VF, Kim CA, Pellegrino R, Takeno SS, Spinner NB, Conlin LK, Christofolini DM, Kulikowski LD, Melaragno MI. Mechanisms of ring chromosome formation, ring instability and clinical consequences. BMC Med Genet 12(1):171. https://doi.org/10.1186/1471-2350-12-171

  • Gutkowska A, Krajewska-Walasek M, Wiśniewski L (1985) Ring chromosome 4: 46,XY,r (4)(p16q35) in a boy. Klin Padiatr 197(4):294–296. https://doi.org/10.1055/s-2008-1033986

  • Halal F, Vekemans M (1990) Ring chromosome 4 in a child with duodenal atresia. Am J Med Genet 37(1):79–82. https://doi.org/10.1002/ajmg.1320370118

  • Hirschhorn K, Herbert LC, Firschein IL (1965) Deletion of short arms of chromosome 4–5 in a child with defects of midline fusion. Hum Genet 1(5):479-482. https://doi.org/10.1007/BF00279124

  • Hou JW, Wang TR (1996) Amelia, dextrocardia, asplenia, and congenital short bowel in deleted ring chromosome 4. J Med Genet 33(10):879–881. https://doi.org/10.1136/jmg.33.10.879

  • Kim JH, Oh PS, Na HY, Kim S-H, Cho HC (2009) A case of mosaic ring chromosome 4 with subtelomeric 4p deletion. Ann Lab Med 29(1):77–81. https://doi.org/10.3343/kjlm.2009.29.1.77

  • Kishi Y, Ikeda H (2018) A case of thumb polydactyly which ulnar thumb has no active motion in ring chromosome 4. J Hand Surg Asian-Pac 23(4):566–570. https://doi.org/10.1142/s2424835518720311

  • Kocks A, Endele S, Heller R, Schröder B, Schäfer H, Städtler C, Makrigeorgi-Butera M, Winterpacht A (2002) Partial deletion of 4p and 4q in a fetus with ring chromosome 4: Phenotype and molecular mapping of the breakpoints. 39(5):23e–223. https://doi.org/10.1136/jmg.39.5.e23

  • Kosztolányi G (1985) Ring chromosome 4: Wolf syndrome and unspecific developmental anomalies. Acta Paediatr Hung 26(2):157–165

    Google Scholar 

  • Kosztolányi G, Opitz JM, Reynolds JF (1987) Decreased cell viability of fibroblasts from two patients with a ring chromosome: An in vitro reflection of growth failure? Am J Med Genet 28(1):181–184. https://doi.org/10.1002/ajmg.1320280125

  • Laleye A, Alao MJ, Adjagba M, Hans C, Delneste D, Gnamey DK, Ayivi B, Darboux RB (2006) Wolf Hirshhorn syndrome in a case of ring chromosome 4: Phenotype and molecular cytogenetic findings. Genet Couns 17(1):35–40

    Google Scholar 

  • Lee MH, Park SY, Kim YM, Kim JM, Yoo KJ, Lee HH, Ryu HM (2005) Molecular cytogenetic characterization of ring chromosome 4 in a female having a chromosomally normal child. Cytogenet Genome Res 111(2):175–178. https://doi.org/10.1159/000086389

  • Lin AE, Garver KL, Diggans G, Clemens M, Wenger SL, Steele MW, Jones MC, Israel J, Opitz JM, Reynolds JF (1988) Interstitial and terminal deletions of the long arm of chromosome 4: Further delineation of phenotypes. Am J Med Genet 31(3):533–548. https://doi.org/10.1002/ajmg.1320310308

  • Lyu Y, Song F, Zhang K, Gao M, Ma J, Wang D, Wan Y, Liu Y, Gai Z (2020) Analysis of clinical and genetic characteristics of a child with ring chromosome 4 syndrome. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 37(8):843–846. https://doi.org/10.3760/cma.j.issn.1003-9406.2020.08.009

  • McDermott A, Voyce MA, Romain D (1977) Ring chromosome 4. J Med Genet 14(3):228–232. https://doi.org/10.1136/jmg.14.3.228

  • Niss R, Passarge E (1975) Derivative chromosomal structures from a ring chromosome 4. Hum Genet 28(1):9–23. https://doi.org/10.1007/bf00272478

  • Parker CE, Alfi O, Derencsenyi A, Mavalwala J, Donnell G (1974) A child with a ring-4 chromosome (46, XX/46, XX, r 4). Arch Pediatr Adolesc Med 128(3):371–374. https://doi.org/10.1001/archpedi.1974.02110280101015

  • Paththinige CS, Sirisena ND, Kariyawasam UGIU, Saman Kumara LPC, Dissanayake VHW (2016) Ring chromosome 4 in a child with multiple congenital abnormalities: A case report and review of the literature. Case Rep Genet 2016(1):1–7. https://doi.org/10.1155/2016/4645716

  • Paz-y-Miño C, Proaño A, Verdezoto SD, García JL, Hernández-Rivas JM, Leone PE (2019) Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: Case report and literature review. BMC Med Genomics 12(1):167. https://doi.org/10.1186/s12920-019-0614-4

  • Perez-Castillo A, Abrisqueta JA (1977) Ring chromosome 4 and Wolf syndrome. Hum Genet 37(1):87–91. https://doi.org/10.1007/bf00293777

  • Phillips EA, Caluseriu O, Schlade-Bartusiak K, Chernos J, McLeod DR, Thomas MA (2021) Clinical and molecular characterization of an almost complete ring chromosome 4 in two sisters, with recurrence due to gonadal mosaicism. 30(4):173–176. https://doi.org/10.1097/mcd.0000000000000382

  • Sherer D, Shah Y, Wang N, Metlay L, Woods J (1991) Prenatal diagnosis and subsequent management of a fetus with a 46XY r(4)(p15–q35) karyotype. Amer J Perinatol 8(1):53–55. https://doi.org/10.1055/s-2007-999342

  • Sigurdardottir S, Goodman BK, Rutberg J, Thomas GH, Jabs EW, Geraghty MT (1999) Clinical, cytogenetic, and fluorescence in situ hybridization findings in two cases of complete ring syndrome. Am J Med Genet 87(5):384–390. https://doi.org/10.1002/(sici)1096-8628(19991222)87:53.0.co;2-r

  • Sodré CP, Guilherme RS, Meloni VFA, Brunoni D, Juliano Y, Andrade JAD, Belangero SIN, Christofolini DM, Kulikowski LD, Melaragno MI (2010) Ring chromosome instability evaluation in six patients with autosomal rings. Genet Mol Res 9(1):134–143. https://doi.org/10.4238/vol9-1gmr707

  • South ST, Bleyl SB, Carey JC (2007) Two unique patients with novel microdeletions in 4p16.3 that exclude the WHS critical regions: Implications for critical region designation. Am J Med Genet 143A(18):2137–2142. https://doi.org/10.1002/ajmg.a.31900

  • Soysal Y, Balci S, Hekimler K, Liehr T, Ewers E, Schoumans J, Bui TH, Içduygu FM, Kosyakova N, Imirzalioğlu N (2009) Characterization of double ring chromosome 4 mosaicism associated with bilateral hip dislocation, cortical dysgenesis, and epilepsy. Am J Med Genet 149A(12):2782–2787. https://doi.org/10.1002/ajmg.a.33069

  • Surana RB, Bailey JD, Conen PE (1971) A ring-4 chromosome in a patient with normal intelligence and short stature. J Med Genet 8(4):517–521. https://doi.org/10.1136/jmg.8.4.517

  • Yao Q, Wang L, Yao B, Gao H, Li W, Xia X, Shi Q, Cui Y (2014) Meiotic prophase I defects in an oligospermic man with Wolf-Hirschhorn syndrome with ring chromosome 4. Mol Cytogenet 7(1):45. https://doi.org/10.1186/1755-8166-7-45

  • Young RS, Zalneraitis EL (1980) Neurological and neuropathological findings in ring chromosome 4. J Med Genet 17(6):487–490. https://doi.org/10.1136/jmg.17.6.487

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Kathleen M. Bone

  2. Department of Medical Genetics, University of Calgary, Calgary, AB, Canada

    Judy Chernos

  3. Departments of Medical Genetics and Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Mary Ann Thomas

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  1. Kathleen M. Bone
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  2. Judy Chernos
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Correspondence to Mary Ann Thomas .

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Editors and Affiliations

  1. Laboratory of Clinical Cytogenetics, Department of Genetics, Yale School of Medicine, New Haven, CT, USA

    Peining Li

  2. Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Jena, Germany

    Thomas Liehr

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Bone, K.M., Chernos, J., Thomas, M.A. (2024). Ring Chromosome 4. In: Li, P., Liehr, T. (eds) Human Ring Chromosomes. Springer, Cham. https://doi.org/10.1007/978-3-031-47530-6_8

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