Journal List > Korean J Lab Med > v.29(1) > 1011608

Korean J Lab Med. 2009 Feb;29(1):77-81. Korean.
Published online February 28, 2009.
Copyright © 2009 The Korean Society for Laboratory Medicine
A Case of Mosaic Ring Chromosome 4 with Subtelomeric 4p Deletion
Jeong Hyun Kim, M.D.,1 Phil Soo Oh, M.D.,2 Hye Yeon Na, M.D.,2 Sun-Hee Kim, M.D.,1 and Hyoun Chan Cho, M.D.3
1Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2Department of Pediatrics, Hallym University School of Medicine, Seoul, Korea.
3Department of Laboratory Medicine, Hallym University School of Medicine, Seoul, Korea.

Corresponding author: Phil Soo Oh, M.D. Department of Pediatrics, Hallym University Medical Center, 94-200 Yeongdeungpo-dong 2-ga, Yeongdeungpo-gu, Seoul 150-719, Korea. Tel: +82-2-2639-5200, Fax: +82-2-2636-1008, Email:
Received September 25, 2008; Revised December 24, 2008; Accepted December 30, 2008.


Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2]]. FISH study showed the deletion of the 4p subtelomeric region with the intact 4q subtelomeric and WHS region. Both paternal and maternal karyotypes were normal. We compared the phenotypic variation with the previously reported cases of ring chromosome 4. The ring chromosome 4 with the subtelomeric deletion of short arm seems to be related with the phenotype of short stature.

Keywords: r(4) chromosome; Mosaic ring chromosome; Short stature


Fig. 1
Brain MRI showing multifocal leukomalacia in the bilateral occipito-parietal, right temporal and bilateral frontal lobes (A) and venous angioma in the left frontal lobe (B).
Click for larger image

Fig. 2
(A) Giemsa-banding karyogram of peripheral blood cells: 46,XY,r(4)(p16q35). (B) Partial karyogram showing normal chromosome 4 (left side) and dic r(4;4)(p16q35;p16q35) A (right side).
Click for larger image

Fig. 3
Metaphase FISH of peripheral blood cells using a 4p subtelomeric probe (Cytocell, UK), 4q subtelomeric and WHS probes (Abbott Molecular/Vysis, USA). (A) The single green color indicates deletion of a 4p subtelomere. (B, C) Intact 4q and WHS probes were detected.
Click for larger image

1. Gardner RJ, Sutherland GR, editors. Chromosome abnormalities and genetic counseling. 3rd ed. Oxford: Oxford University Press; 2004. pp. 178-181.
2. Shashi V, White JR, Pettenati MJ, Root SK, Bell WL. Ring chromosome 17: phenotype variation by deletion size. Clin Genet 2003;64:361–365.
3. Bergemann AD, Cole F, Hirschhorn K. The etiology of Wolf-Hirschhorn syndrome. Trends Genet 2005;21:188–195.
4. Rauch A, Schellmoser S, Kraus C, Dorr HG, Trautmann U, Altherr MR, et al. First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation. Am J Med Genet 2001;99:338–342.
5. Kosztolanyi G. Does "ring syndrome" exist? An analysis of 207 case reports on patients with a ring autosome. Hum Genet 1987;75:174–179.
6. Kim SS, Jung SC, Kim HJ, Moon HR, Lee JS. Chromosome abnormalities in a referred population for suspected chromosomal aberrations: a report of 4117 cases. J Korean Med Sci 1999;14:373–376.
7. Hwang SJ, Lee JH, Park IY, Moon HB, Oh JH, Lee GS, et al. A case of de novo ring (13) chromosome with deletion 13q32.2→qter. Korean J Obstet Gynecol 2002;45:323–326.
8. Park YM, Nho HN, Kim SZ, Ahn YM. Cytogenetic evaluation of a patient with ring chromosome 9 presenting failure to thrive and developmental delay. Korean J Pediatr 2008;51:426–430.
9. Jung YK, Lee GH. A case of ring chromosome 20 with mental retardation and epilepsy. Korean J Pediatr 2005;48:108–111.
10. Lee MH, Park SY, Kim YM, Kim JM, Yoo KJ, Lee HH, et al. Molecular cytogenetic characterization of ring chromosome 4 in a female having a chromosomally normal child. Cytogenet Genome Res 2005;111:175–178.
11. Blackett PR, Li S, Mulvihill JJ. Ring chromosome 4 in a patient with early onset type 2 diabetes, deafness, and developmental delay. Am J Med Genet A 2005;137:213–216.
12. Balci S, Engiz O, Aktas D, Vargel I, Beksac MS, Mrasek K, et al. Ring chromosome 4 and Wolf-Hirschhorn syndrome (WHS) in a child with multiple anomalies. Am J Med Genet A 2006;140:628–632.
13. Laleye A, Alao MJ, Adjagba M, Hans C, Delneste D, Gnamey DK, et al. Wolf Hirshhorn syndrome in a case of ring chromosome 4: phenotype and molecular cytogenetic findings. Genet Couns 2006;17:35–40.
14. Wieczorek D, Krause M, Majewski F, Albrecht B, Horn D, Riess O, et al. Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn syndrome: analysis of 13 patients with a de novo deletion. Eur J Hum Genet 2000;8:519–526.
15. Dietze I, Fritz B, Huhle D, Simoens W, Piecha E, Rehder H. Clinical, cytogenetic and molecular investigation in a fetus with Wolf-Hirschhorn syndrome with paternally derived 4p deletion. Case report and review of the literature. Fetal Diagn Ther 2004;19:251–260.
16. Chitayat D, Ruvalcaba RH, Babul R, Teshima IE, Posnick JC, Vekemans MJ, et al. Syndrome of proximal interstitial deletion 4p15: report of three cases and review of the literature. Am J Med Genet 1995;55:147–154.
17. Van Buggenhout G, Melotte C, Dutta B, Froyen G, Van Hummelen P, Marynen P, et al. Mild Wolf-Hirschhorn syndrome: micro-array CGH analysis of atypical 4p16.3 deletions enables refinement of the genotype-phenotype map. J Med Genet 2004;41:691–698.
18. White DM, Pillers DA, Reiss JA, Brown MG, Magenis RE. Interstitial deletions of the short arm of chromosome 4 in patients with a similar combination of multiple minor anomalies and mental retardation. Am J Med Genet 1995;57:588–597.
19. Concolino D, Rossi E, Strisciuglio P, Iembo MA, Giorda R, Ciccone R, et al. Deletion of a 760 kb region at 4p16 determines the prenatal and postnatal growth retardation characteristic of Wolf-Hirschhorn syndrome. J Med Genet 2007;44:647–650.
20. Moretti P, Ferrari M, Di Battista S, Di Battista C. The 4P-syndrome. Case description and literature review. Minerva Pediatr 2001;53:23–28.
21. Dufke A, Seidel J, Schoning M, Dobler-Neumann M, Kelbova C, Liehr T, et al. Microdeletion 4p16.3 in three unrelated patients with Wolf-Hirschhorn syndrome. Cytogenet Cell Genet 2000;91:81–84.
22. Nakayama J, Hamano K, Shimakura Y, Iwasaki N, Nakahara C, Imoto N, et al. Abnormal myelination in a patient with ring chromosome 18. Neuropediatrics 1997;28:335–337.