Clinical phenotype and diagnostic pathways of 22q11.2 deletion syndrome in a Ukrainian cohort
15 affiliations
- 1Department of Children’s Diseases and Pediatric Surgery, I.Horbachevsky Ternopil National Medical University
- 2Department of Pediatrics, Immunology, Infectious and Rare Diseases, European Medical School, First European University
- 3Department of Pediatrics, Medspace Clinic
- 4Department of Clinical Immunology and Allergology, Danylo Halytsky Lviv National Medical University
- 5Department of Pediatrics, Cherkasy Regional Children’s Hospital
- 6Department of Propedeutics of Pediatric Diseases with Patient Care, National Pirogov Memorial Medical University
- 7Department of Pediatrics Oncohematology, Volyn Regional Territorial Mother and Child Health Care Center
- 8Department of Pediatrics, Clinical Center of Children’s Medicine
- 9Center for Oncohematology, Immunology and Metabolic Disorders, Rivne Regional Children’s Hospital
- 10Outpatient Department, Zakarpattia Regional Children’s Hospital
- 11Department of Pediatrics, Ivano-Frankivsk National Medical University
- 12Department of Pediatrics, Chernihiv Regional Children’s Hospital
- 13Regional Center of Neonatal Screening, Lviv Regional Clinical Perinatal Center
- 14Department of the Research and Biotechnology, Scientific Medical Genetic Center LeoGENE
- 15Center of Genetic Diagnostics and Cell Immunotherapy, National Specialized Children’s Hospital “OHMATDYT”
Abstract
Introduction: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a common multisystem genomic disorder with marked phenotypic variability and diagnostic delay. Data on diagnostic pathways and specialist involvement in Eastern Europe remain limited. We aimed to characterize diagnostic pathways and clinical triggers, assess specialist involvement and follow-up, and identify factors associated with diagnosis before or after 1 year of age in a Ukrainian cohort.
Methods: We conducted a retrospective multicenter observational study of patients with 22q11.2DS registered in the Ukrainian National Registry of Primary Immunodeficiencies. Clinical manifestations, diagnostic triggers, specialists involved in diagnosis and follow-up, immunological findings, and age at diagnosis were analyzed.
Results: The cohort included 126 patients, with a median age of 12 years (range, 0.1–39 years) and median age at diagnosis of 1.0 year (range, 0.1–18 years). Among 120 patients with available diagnostic timing, 63 (52.5%) were diagnosed within the first year, including the two antenatal cases. Congenital heart disease (CHD) was the most frequent major manifestation (74/89, 83.1%), followed by craniofacial dysmorphism (62/74, 83.8%), thymic hypoplasia (54/65, 83.1%), developmental delay (46/62, 74.2%), and recurrent infections (44/65, 67.7%). Among 83 patients with documented diagnostic triggers, CHD was the most frequent (61/83, 73.5%). Developmental delay was more frequent among patients diagnosed after 1 year than within the first year (22.9% vs. 4.4%, p = 0.0135). Immunodeficiency was a diagnostic trigger in 10/83 patients (12.0%), despite T-cell lymphopenia in 31/59 (52.5%). Immunologists and geneticists were most frequently involved in diagnosis. Cardiothoracic surgeons and cardiologists were more frequently involved among patients diagnosed within the first year than after 1 year (27.9% vs. 9.1%, p = 0.0411). Among 13 patients diagnosed after implementation of TREC/KREC newborn screening, two were identified following an abnormal screening result.
Conclusions: In this Ukrainian cohort, 22q11.2DS diagnosis was predominantly phenotype-driven, with CHD representing the principal diagnostic trigger. Developmental delay was associated with diagnosis after 1 year, whereas immunological abnormalities relatively infrequently initiated diagnostic evaluation. Broader recognition of non-cardiac presentations, standardized referral criteria, coordinated multidisciplinary care, and continued development of newborn and prenatal screening may improve timely diagnosis of 22q11.2DS in Ukraine.
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BibTeX
@article{boyarchuk2026clinical,
title = {{Clinical phenotype and diagnostic pathways of 22q11.2 deletion syndrome in a Ukrainian cohort}},
author = {Oksana Boyarchuk and Anastasiia Bondarenko and Anna Hilfanova and Yaryna Romanyshyn and Liliia Nazarenko and Oksana Tykholaz and Mariana Lazaruk and Nataliia Yarema and Liubov Volianska and Tetyana Hariyan and Maria Kinash and Tetiana Kovalchuk and Ihor Savchak and Oksana Malko and Tetiana Tsanko and Olha Urbas and Iryna Hrabovska and Svitlana Kalyuzhko and Iryna Polishchuk and Halyna Makukh and Nataliia Olkhovych},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1989465},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1989465/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Clinical phenotype and diagnostic pathways of 22q11.2 deletion syndrome in a Ukrainian cohort
AU - Oksana Boyarchuk
AU - Anastasiia Bondarenko
AU - Anna Hilfanova
AU - Yaryna Romanyshyn
AU - Liliia Nazarenko
AU - Oksana Tykholaz
AU - Mariana Lazaruk
AU - Nataliia Yarema
AU - Liubov Volianska
AU - Tetyana Hariyan
AU - Maria Kinash
AU - Tetiana Kovalchuk
AU - Ihor Savchak
AU - Oksana Malko
AU - Tetiana Tsanko
AU - Olha Urbas
AU - Iryna Hrabovska
AU - Svitlana Kalyuzhko
AU - Iryna Polishchuk
AU - Halyna Makukh
AU - Nataliia Olkhovych
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1989465
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1989465/full
AB - Introduction: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a common multisystem genomic disorder with marked phenotypic variability and diagnostic delay. Data on diagnostic pathways and specialist involvement in Eastern Europe remain limited. We aimed to characterize diagnostic pathways and clinical triggers, assess specialist involvement and follow-up, and identify factors associated with diagnosis before or after 1 year of age in a Ukrainian cohort. Methods: We conducted a retrospective multicenter observational study of patients with 22q11.2DS registered in the Ukrainian National Registry of Primary Immunodeficiencies. Clinical manifestations, diagnostic triggers, specialists involved in diagnosis and follow-up, immunological findings, and age at diagnosis were analyzed. Results: The cohort included 126 patients, with a median age of 12 years (range, 0.1–39 years) and median age at diagnosis of 1.0 year (range, 0.1–18 years). Among 120 patients with available diagnostic timing, 63 (52.5%) were diagnosed within the first year, including the two antenatal cases. Congenital heart disease (CHD) was the most frequent major manifestation (74/89, 83.1%), followed by craniofacial dysmorphism (62/74, 83.8%), thymic hypoplasia (54/65, 83.1%), developmental delay (46/62, 74.2%), and recurrent infections (44/65, 67.7%). Among 83 patients with documented diagnostic triggers, CHD was the most frequent (61/83, 73.5%). Developmental delay was more frequent among patients diagnosed after 1 year than within the first year (22.9% vs. 4.4%, p = 0.0135). Immunodeficiency was a diagnostic trigger in 10/83 patients (12.0%), despite T-cell lymphopenia in 31/59 (52.5%). Immunologists and geneticists were most frequently involved in diagnosis. Cardiothoracic surgeons and cardiologists were more frequently involved among patients diagnosed within the first year than after 1 year (27.9% vs. 9.1%, p = 0.0411). Among 13 patients diagnosed after implementation of TREC/KREC newborn screening, two were identified following an abnormal screening result. Conclusions: In this Ukrainian cohort, 22q11.2DS diagnosis was predominantly phenotype-driven, with CHD representing the principal diagnostic trigger. Developmental delay was associated with diagnosis after 1 year, whereas immunological abnormalities relatively infrequently initiated diagnostic evaluation. Broader recognition of non-cardiac presentations, standardized referral criteria, coordinated multidisciplinary care, and continued development of newborn and prenatal screening may improve timely diagnosis of 22q11.2DS in Ukraine.
SN - 1664-3224
ER -