Ring Chromosome 22

Ring chromosome 22 is a rare chromosomal arrangement where the long arm and short arm of a singular chromosome 22 are joined together. This causes the entire chromosome to be in a circular, or ring, structure rather than linear. This joining process results in the deletion of some genetic material, frequently resulting in a clinical picture similar to various 22q deletions¹.

The most common deleted material of ring chromosome 22 includes the SHANK3 gene, located within 22q13.3, which causes Phelan-McDermid syndrome (PMS)². PMS is a neurodevelopmental disorder that causes variable features including intellectual and developmental delays, delayed growth, behavioral differences, and some dysmorphic features³. Intellectual delays in these individuals can range from moderate to severe, although speech is largely absent or severely delayed². There is also a high incidence of impaired adaptive behaviors, autism spectrum disorder, and potentially other mood disorders including bipolar disorder, hyperactivity, and aggressive behaviors^1,4.

PMS may also present with various dysmorphic features including epicanthus, large and dysplastic ears, long eyelashes, full eyebrows, hypertelorism, bulbous nose, pointed chin, and high arched palate³. Renal anomalies and congenital heart defects may also be seen. This includes cystic kidneys, dysplastic kidney, renal stones, ureteric reflux, atrial septal defect, tricuspid valve regurgitation, patent ductus arteriosus, and pulmonary return³.

Less commonly, ring chromosome 22 deletions may expand beyond the 22q13.3 region and include neighboring segments, such as the NF2 gene. In these individuals, they will have additional symptoms of neurofibromatosis type 2¹.

Other individuals with ring chromosome 22 have presented with atypical teratoid rhabdoid tumors. Typically, these tumors are due to somatic variants in the tumor suppressor gene SMARCB1⁵. SMARCB1 is located at 22q11.2. However, case reports have shown individuals with ring chromosome 22 whose deletions do not include the SMARCB1 gene, yet still have atypical teratoid rhabdoid tumors^5,6. It is thought that ring chromosome 22 is inherently unstable and may be prone to abnormal mitotic movements, creating somatic mosaicism for monosomy chromosome 22^5,6.

REFERENCES

¹Droogmans G, Swillen A, Van Buggenhout G. (2020). Deep phenotyping of development, communication and behaviour in Phelan-McDermid Syndrome. Mol Syndromol. 10(6): 294–305.

²Crocco M, Panciroli M, Milanaccio C, et al. (2021). Case Report: The emerging role of ring chromosome 22 in Phelan-McDermid Syndrome with atypical teratoid/rhabdoid tumor: The first child treated with growth hormone. Front Neurol. 12:741062.

³Ismail S, Kamel AK, Ashaat EA, et al. (2018). Clinical and cytogenetic analysis of terminal 22q13.3 deletion in two patients with ring chromsome 22. Middle East J Med Genet. 7:139-144.

⁴Guilherme RS, Soares KC, Simioni M, et al. (2014). Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion. Am J Med Genet A.164A(7):1659–1665.

⁵Byers HM, Adam MP, LaCroix A, et al. (2017). Description of a new oncogenic mechanism for atypical teratoid rhabdoid tumors in patients with ring chromosome 22. Am J Med Genet A. 173(1):245–249.

⁶Lee JC, Tran QT, McGee RB, et al. (2024). Atypical teratoid/rhabdoid tumour-TYR subtype arising in the setting of germline ring chromosome 22: An uncommon form of tumour predisposition. Neuropathol Appl Neurobiol. 50(2):e12971.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. Review and formatting by Lydia Bentley, MS CGC. For more information on any article please contact info@chromodisorder.org