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 A. 2017 Mar;173(3):727-732. doi: 10.1002/ajmg.a.38063. Epub 2017 Jan 27.


Constitutional ring chromosomes can be found for all human chromosomes and are very rare chromosomal abnormalities. A complete ring chromosome without loss of genetic material results from fusion of subtelomeric regions or telomere-telomere fusion. In cases of complete ring chromosome, an increased incidence of severe growth failure with no or only minor anomalies has been observed and attributed to ring syndrome. Ring syndrome is thought to be caused by "dynamic mosaicism" due to ring instability. We report a 6-year-old boy with de novo ring chromosome 4 and typical characteristics of the ring syndrome, namely, proportionate severe growth failure, microcephaly, and minor anomalies. Cytogenetic studies showed complete ring chromosome 4 with mitotic instability. Microarray gave normal results, thus excluding the loss of detectable genetic material. The literature of complete ring chromosome 4 is reviewed. Our case report supports the theory of ring syndrome. No studies about the effects and possible side effects of growth hormone therapy on patients with ring chromosomes have yet been published. We suggest that cytogenetic monitoring of the rate of secondary aberrations in patients with ring chromosome undergoing growth hormone therapy might be feasible. Since the diagnosis would have been missed by molecular karyotyping, our case report underlines the continuing role of classical cytogenetics for the evaluation of structural chromosomal abnormalities in patients with mental and/or physical anomalies. Standard karyotyping is still indispensable and should have an ongoing role as first-tier analysis together with molecular karyotyping. © 2017 Wiley Periodicals, Inc.

Keywords: complete ring chromosome 4; ring syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child
  • Chromosome Aberrations
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics*
  • Chromosomes, Human, Pair 4 / genetics
  • Comparative Genomic Hybridization
  • Cytogenetic Analysis* / methods
  • Facies
  • Genetic Association Studies
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Male
  • Phenotype
  • Ring Chromosomes

Supplementary concepts

  • Ring chromosome 4 syndrome