Ring X Chromosome

Ring X chromosome is a rare chromosomal arrangement where the long arm and short arm of a singular X chromosome are joined together. This causes the entire chromosome to be in a circular, or ring, structure rather than linear. Patients with ring X chromosome show clinical manifestations of Turner syndrome. Turner syndrome is characterized by the presence of one X chromosome and either the complete loss of the second sex chromosome or partial loss of the second X chromosome¹. In the case of ring X chromosome, there are likely deletions of both the long and short arm prior to their fusion². Usually, patients with ring X chromosome are mosaics. This means some cells contain a ring X chromosome, while, in other cells, one of the X chromosomes is completely absent [45,X/46,X,r(X)]. Another variant of mosaicism: combination of the clone with a ring chromosome and a normal 46,XX clone is rarer.

Individuals with Turner syndrome due to ring X chromosome may present with neuropsychological challenges, cardiac and/or renal anomalies, endocrine concerns, and autoimmune conditions¹.

Intellectual or developmental delays may be present in those with Turner syndrome, however, individuals who have Turner syndrome due to a ring X chromosome are more likely to present with severe delays². Individuals with ring X chromosome are more likely to have lower performance and verbal IQs and have an increased likelihood of presenting with other intellectual delays³. This difference in intellectual and developmental delays is likely due to the deletion of the XIST gene on the short arm of the X chromosome3. Without this gene, the X chromosome cannot undergo a process called X-inactivation, which results in abnormal expression of the X chromosome³.

Individuals with Turner syndrome may also present with various cardiac anomalies. This may include bicuspid aortic valve, aortic dilation, hypertension, coarctation of the aorta, patent ductus arteriosus, atrial septal defect, and ventricular septal defect¹. One case reported identified a patient with ring X chromosome to have idiopathic dilated cardiomyopathy, a cardiac finding that is relatively rare for Turner syndrome³. It should be noted, however, that individuals with Turner syndrome due to a ring X chromosome have a reduced frequency of having a bicuspid aortic valve¹.

In addition to cardiac anomalies, some renal anomalies may also be present. Findings such as renal malrotation, duplicated collecting system, and a pelvic kidney have all been identified².

Other key aspects of Turner syndrome are the endocrine anomalies and delayed sexual development. Many individuals with Turner syndrome present with growth hormone deficiency resulting in short stature². It is also common for individuals to have gonadal dysgenesis, resulting in a lack of menstrual periods or infertility². Additionally, it is common for there to be delayed development of secondary sexual characteristics².

Several other common features identified in those with Turner syndrome include a low posterior hairline, widely spaced nipples, neck webbing, and autoimmune disease. Autoimmune disease may include diagnoses of Celiac disease, Graves’ disease, Hashimoto thyroiditis, or type 1 diabetes².

While there are a wide range of clinical features possible, it is important to note the factors that can influence severity. For example, the size of the ring or, rather, how much genetic information is deleted from the ends of the long and short arms of the X chromosome influences severity. Individuals with smaller rings (or larger deletions) are more likely to have severe clinical features². Individuals who have more cells that contain a ring X chromosome are more likely to have severe clinical findings compared to individuals who have fewer cells that contain a ring X chromosome¹.

References

¹Cicione ME, Wong AW, Aragon E, et al. (2025). Revisiting the neuropsychological and clinical profile of mosaic Turner syndrome with a ring X chromosome. Am J Med Genet C Semin Med Genet. Advance online publication.
²Madison A, Applegate C, Stinnett V, et al. (2025). Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution. Sci Rep. 15(1):12836.
³Das D, Roy D, Basu K, Sarkar A. (2021). Decoding enigma: Turner syndrome with ring chromosome. Oxf Med Case Reports 11, 457-460.