title: Continuing role for classical cytogenetics: Case report of a boy with ring syndrome caused by complete ring chromosome 4 and review of literature.
abstract: 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.
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Burgemeister
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Daumiller
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Dietze-Armana
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Klett
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Pediatric Endocrinology, University Medicine, Göttingen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Freiberg
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Pediatric Neurology, University Medicine, Göttingen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Stark
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Pediatric Neurology, University Medicine, Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lingen
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Izabela
authors.initials: I
authors.lastname: Centonze
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Rettenberger
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Mehnert
authors.affiliation: Genetikum, Genetic Counseling and Diagnostics, Stuttgart and Neu-Ulm, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Zirn
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis / Q000379:methods; D019066:Facies; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D010641:Phenotype; D012303:Ring Chromosomes
keywords: complete ring chromosome 4; ring syndrome