| Summary: | Abstract Background Constitutional ring chromosomes are rare orphan chromosomal disorders. Ring chromosome syndrome featuring growth retardation and mild to intermediate intellectual disability is likely caused by the dynamic behavior of ring chromosome through cell cycles. Chromosomal and regional specific phenotypes likely result from segmental losses and gains during the ring formation. Although recent applications of genomic copy number and sequencing analyses revealed various ring chromosome structures from an increasing number of case studies, there was no organized effort for compilating and curating cytogenomic and clinical finding for ring chromosomes. Methods A web-based interactive ‘Human Ring Chromosome Registry’ using Microsoft Access based relational database was developed to present genetic and phenotypic findings of ring chromosome cases. Chinese ring chromosome cases reported in the literature was reviewed and compiled as a testing data set to validate this registry. Results A total of 113 cases of ring chromosomes were retrieved in all chromosomes except for chromosomes 16, 17 and 19. The most frequently seen ring chromosomes by a decreasing order of relative frequencies were ring 13 (14%), X (12%), 22 (10%), 15 (9%), 14 (7%), and 18 (7%). Genomic imbalances were detected in 18 out of 19 cases analyzed by microarray or sequencing. Variable clinical manifestations of developmental delay, dysmorphic facial features, intellectual disability, microcephaly, and hypotonia were noted in most autosomal rings. Chromosomal specific syndromic phenotypes included Wolf-Hirschhorn syndrome in a ring chromosome 4, cri-du-chat syndrome in a ring chromosome 5, epilepsy in ring chromosomes 14 and 20, Turner syndrome in ring chromosome X, and infertility in ring chromosomes 13, 21, 22 and Y. Effective growth hormone supplemental treatment for growth retardation in a ring chromosome 18 was noted. Conclusions Based on findings from these Chinese ring chromosome cases, guidelines for cytogenomic diagnosis and criteria for case registration were proposed. Further research to define underlying mechanisms of ring chromosome formation and dynamic mosaicism, to delineate the genotype-phenotype correlations, and to develop chromosome therapy for ring chromosomes were discussed.
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