Ring chromosome 21 and reproductive pattern: a familial case and review of the literature

Unique Genomic Structure and Distinct Mitotic Behavior of Ring Chromosome 21 in Two Unrelated Cases

“…A relatively normal phenotype from a ring chromosome 21 with minimal mitotic instability and absence of a terminal deletion or duplication has been reported [Papoulidis et al, 2010]. Ring chromosomes 21 with defined 3-5-Mb distal deletions and minimal mitotic instability were responsible for mild to moderate dysmorphic features and prenatal intrauterine growth retardation [Ki et al, 2003;Bertini et al, 2008]. Ring chromosomes 21 involving segmental duplication of critical regions could predict a Down syndrome or Down syndrome-like phenotype [Crombez et al, 2005].…”

“…The patient presented with dysmorphic features, hypotonia, and symptoms of connective tissue disorder. Hypoinsufficiency of the COL6A1 , COL6A2 , and COL18A genes at 21q22.3 has been thought to be responsible for a connective tissue defect [Rope et al, 2004], but the absence of this defect has also been reported in cases with defined deletions of this region [Bertini et al, 2008].…”

“…The patient presented with severe growth and mental retardation, dysmorphic features, and intractable seizures. A recent study in an adult patient and review of familial cases of ring chromosome 21 showed that approximately 50% of r(21) males had azoospermia or infertility, 28% of r(21) females had spontaneous abortions, and among the offspring from affected females, 37% had a normal karyotype, 37% had a transmitted r(21) and a normal phenotype, and 26% had either variable phenotypes ranging from mild dysmorphic features to growth retardation or Down syndromelike phenotype due to an extra or a duplicated ring chromosome 21 [Bertini et al, 2008].…”

“…abnormal phenotype, simple distal deletion in r(21), and variable mitotic instability [Ki et al, 2003;Bertini et al, 2008] III. Down syndrome-like phenotype, an extra r(21) or large duplicated r(21) with variable mitotic instability [Crombez et al, 2005] IV.…”

“…Recently, genome-wide oligonucleotide array comparative hybridization (aCGH) has been validated for clinical diagnosis and proven to be highly effective in defining the breakpoints and gene content of chromosomal imbalances [Xiang et al, 2008]. The application of genomic analysis defined a simple distal deletion of ring chromosome 21 in 3 cases [Ki et al, 2003;Bertini et al, 2008;Fiorini et al, 2009] and a complete ring chromosome 21 in a fetus [Papoulidis et al, 2010]. In this report, we present the unique cytogenetic and genomic findings from 2 unrelated cases of ring chromosome 21 and propose a cytogenomic approach for further characterization of the genomic structure and mitotic behavior of ring chromosomes 21.…”