IMMUNE DISORDERS IN EDWARDS SYNDROME IN CHILDREN

Edwards syndrome (trisomy 18) is recognized as the second most common autosomal trisomy after Down syndrome and is characterized by pronounced multiorgan pathology affecting virtually all body systems, including the organs of the immune system. Although immune disturbances in this chromosomal anomaly occur frequently and may substantially influence the clinical course of the disease, the morphological diagnosis of these changes in pediatric pathology practice has traditionally received insufficient attention. As a result, important structural alterations in immune organs are often underestimated and rarely considered as a distinct and clinically relevant component of the underlying pathogenesis.

The aim of this study was to conduct a detailed analysis of morphological changes in the organs of the immune system in children diagnosed with Edwards syndrome. The investigation was carried out at the Sverdlovsk Regional Pathology Bureau (SOPAB) in Yekaterinburg, Russia, and included an examination of autopsy materials from ten children who died between 2019 and 2025. A review of their medical records demonstrated that, despite comprehensive clinical evaluations, none of the patients received a premortem diagnosis of immunodeficiency, and this condition was not reflected in the final clinical diagnoses.

Postmortem morphological analysis revealed significant abnormalities in immune organs in 70% of the children. The thymus showed various pathological changes, including hypoplasia (30%), hypoplastic dysplasia with areas of fatty degeneration and lymphoid depletion (10%), and large-cystic hypoplastic dysplasia (10%). The spleen also exhibited alterations in both the quantity and architecture of its lymphoid components. Infectious complications were identified in six children (60%), either as competing conditions or as the direct cause of death. One child presented only with prolonged recurrent pneumonia, while in the remaining cases the infections were generalized. In all instances, infectious processes were associated with severe congenital malformations of organs and systems and/or pronounced structural abnormalities of the thymus.

The findings highlight the importance of further research into immunopathology in patients with chromosomal abnormalities, aiming to enhance diagnostic accuracy at both clinical and pathological stages.

1. Cereda A., Carey J.C. The trisomy 18 syndrome. Orphanet J. Rare Dis., 2012, Vol. 7, p. 81.

2. Rasmussen S.A., Wong L.Y., Yang Q., et al. Population-based analyses of mortality in trisomy 13 and trisomy 18. Pediatrics, 2003, Vol. 111, no. 4, pp. 777–784.

3. Karl K., Heling K.S., Sarut Lopez A., et al. Thymic–thoracic ratio in fetuses with trisomy 21, 18 or 13. Ultrasound Obstet. Gynecol., 2012, Vol. 40, no. 3, pp. 412–417.

4. Makrydimas G., Plachouras N., Thilaganathan B., Nicolaides K.H. Abnormal immunological development in fetuses with trisomy 18. Prenat. Diagn., 1994, Vol. 14, no. 4, pp. 239–241.

5. Gul Y., Kapaklı H., Aytekin S.E., Guner Ş.N., Keles S., Zamani A.G., Yıldırım M.S., Reisli Ï. Evaluation of immunological abnormalities in patients with rare syndromes. Cent. Eur. J. Immunol., 2022, Vol. 47, no. 4, pp. 299–307.

6. Qiu X., et al. Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome. Hum. Genomics, 2021, Vol. 15, p. 40.

7. Stern H.H., Jose J., Bhardwaj N., et al. A case series: Four patients with Trisomy 18 and primary immunodeficiency. J. Allergy Clin. Immunol., 2017.

8. Marsan Suarez V., et al. Síndrome de Edwards asociado a inmunodeficiencia combinada. Rev. Cubana Hematol. Inmunol. Hemoter., 2011, Vol. 27, no. 3, pp. 342–348.

9. Cody J.D., Hale D.E., Brkanac Z., et al. Immune dysregulation in patients with chromosome 18q deletions. Front. Immunol., 2021, Vol. 12, p. 742834.

10. Tamaki S., Iwatani S., Izumi A., et al. Improving survival in patients with trisomy 18. Am. J. Med. Genet. A., 2022, Vol. 188, no. 4, pp. 1048–1055.

11. Carey J., Cody J., Mehl J., Gelfond J. P138: Causes of death and associated factors in patients with trisomy 18 syndrome and long-term survival. Genet. Med. Open., 2023, Vol. 1, no. 1, Supplement.

12. Ferreira de Souza L.M., Galvão E. Brito Medeiros A., Júnior J.P.R., de Melo A.N., Dias S.A.M.M. Long survival of a patient with Trisomy 18 and Dandy-Walker Syndrome. Medicina (Kaunas)., 2019, Vol. 55, no. 7.

13. Balasundaram P., Avulakunta I.D. Edwards Syndrome. In: StatPearls. StatPearls Publishing, Treasure Island (FL), 2025.

14. Hogendorf A., Zieliński M., Constantinou M., et al. Immune dysregulation in patients with chromosome 18q deletions — searching for putative loci for autoimmunity and immunodeficiency. Front. Immunol. 2021, Vol. 12, pp. 742834.

15. Yeganeh M., et al. Primary antibody deficiency associated with ring chromosome 18 (case report / series). LymphoSign / specialty journal, 2019? Vol. 7(1), pp. 25-36