The past, present, and future for constitutional ring chromosomes: A report of the international consortium for human ring chromosomes

Live‐born autosomal ring chromosomes at the Johns Hopkins Hospital Cytogenomics Laboratory: Case series—Spanning 52 years of experience in a single center

“…Patient RC4‐4 shares intellectual disability and dysmorphic features with other RC4 cases. At least thirty‐four cases involving RC4 are described in the literature, most of which involve terminal deletions of genetic material; seventeen share breakpoints at 4p16 and 4q35, and six are non‐mosaic (Li et al, 2022). As no high‐resolution array studies were performed for these cases, additional complexities like the coexistence of chromosome 4 duplication and deletion cannot be excluded.…”

“…In contrast, the predominant cell line observed in RC17‐2 is a mosaic ring (73%) that arose sporadically and was subsequently characterized using chromosomal microarray, confirming a 1.8 Mb terminal deletion of 17p13.3 (Figure 5). At least 21 individuals bearing RC17 have been described (Li et al, 2022). RC17 may confer Miller–Dieker syndrome (MDS)‐associated features such as lissencephaly and severe intellectual disability, and it may confer dysmorphic facial features when the critical region (CR) is involved (Coppola et al, 2017; MIM: 247200).…”

“…Cases are abundant with RC18. At least 110 RC18 cases have been reported (Li et al, 2022). RC18 manifestations, in decreasing frequency, can involve developmental delay, intellectual disability, dysmorphic facial features, speech difficulty, hypothyroidism, microcephaly, hypotonia, hyperactivity or hypoactivity, and growth hormone deficiency (Hu et al, 2018).…”

“…RCX has been associated with characteristics of a Turner syndrome (TS) diagnosis: ovarian dysfunction, short stature, and growth retardation. Notably, RCX in the background of a normal female chromosomal complement (46,X,r(X)/46,XX) is a separate entity from the kind of mosaicism arising secondary to the mitotic instability of the RCX (45,X/46,X,r(X)) (Li et al, 2022). A large RCX with an intact XIST (X-inactive specific transcript) locus would be preferentially inactivated, thereby silencing any imbalance.…”

“…In general, gonosomal RCs may be associated with milder presentations; therefore, this study focused on twenty‐three additional examples of complete autosomal RCs across nine different autosomal chromosomes using historical and current cytogenetic technologies in the constitutional setting. It is estimated that the RC detection rate is 0.06% in present‐day cytogenetics labs (Li et al, 2022). While considered a cytogenetic rarity, this case series is vital to provide information about ring cases to the larger community to aid genotype–phenotype correlations.…”