PhD Scientific Days 2023

Budapest, 22-23 June 2023

Clinical Medicine - Posters J

Co-occuring Genetic Syndromes Modifing the Phenotype of 22q11.2 Microdeletion Syndrome

Tóth-Szumutku Fanni, MD. Semmelweis University, Pediatric Center Tűzoltó street Department, Budapest
Irén Haltrich, MSC, Ph.D., Semmelweis University, Pediatric Center Tűzoltó street Department, Budapest
Árpád Ferenc Kovács, MD., Ph.D. Semmelweis University, Pediatric Center Tűzoltó street Department, Budapest

Text of the abstract

Introduction
22q11.2 microdeletion syndrome is on of the most common microdeletion syndromes, occurring in up to 1 in every 2000 newborns. Its heterogeneous phenotype makes clinical diagnosis challenging. One possible explanation for the variable phenotypic expression could be the existence of a second pathogenic genetic variation in the genome in addition to 22q11.2 deletion.

Aims
Identifying additional genetic syndromes in our cohort of patients who have been diagnosed with 22q11.2 microdeletion syndrome.

Methods
The genetic diagnosis was confirmed with either G-banding, comparative genomic hybridization, multiplex ligation-dependent probe amplification, or fluorescent in situ hybridization. Dual diagnoses were retrospectively identified from our patient cohort followed at the Tűzoltó Street Department of the Pediatric Center, Semmelweis University.

Results
We identified four patients (3 novel cases) with a 22q11.2 deletion and a coexisting genetic condition: one patient with Williams syndrome, one with Kleefstra syndrome, one with X-linked ichtyosis and one with translocation t(3;10). Three of 4 patients presented overlapping phenotypes between their dual diagnoses, while 1 patient demonstrates a distinct secondary phenotype.

Conclusion
We suspect that the rate of dual diagnosis (4 out of 60) may be underestimated as clinicians may stop investigating the cause of unusual symptoms after confirming 22q11.2 microdeletion. This case series highlights the importance of reviewing the symptoms of patients who display features that are not consistent with the diagnosis of 22q11.2 deletion. In contrast to previous findings, our case series indicate that typical 22q11.2 deletions as well as nested deletions may occur alongside other genetic syndromes. Our report underlines the significance of precise molecular diagnostics, which can lead to personalized and appropriate medical treatment, as well as the challenges associated with genetic testing for diagnosing 22q11.2 microdeletion syndrome.

Funding
Our research was funded by For Human Genome Foundation.