Continuing role for classical cytogenetics: Case report of a boy with ring syndrome caused by complete ring chromosome 4 and review of literature

Constitutional ring chromosomescan be found for all human chromosomesand are very rare chromosomal abnormalities. A complete ring chromosomewithout loss of genetic material results from fusion of subtelomericregions 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 ringsyndrome. Ringsyndrome is thought to be caused by “dynamic mosaicism” due to ringinstability. We report a 6-year-old boy with de novo ring chromosome4 and typical characteristics of the ringsyndrome, namely, proportionate severe growth failure, microcephaly, and minor anomalies. Cytogeneticstudies showed complete ring chromosome4 with mitotic instability. Microarray gave normal results, thus excluding the loss of detectable genetic material. The literature of complete ring chromosome4 is reviewed. Our case report supports the theory of ringsyndrome. No studies about the effects and possible side effects of growth hormone therapyon patients with ring chromosomeshave yet been published. We suggest that cytogeneticmonitoring of the rate of secondary aberrations in patients with ring chromosomeundergoing growth hormone therapymight be feasible. Since the diagnosis would have been missed by molecular karyotyping, our case report underlines the continuing role of classical cytogeneticsfor the evaluation of structural chromosomal abnormalitiesin 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. © 2016 Wiley Periodicals, Inc.