Articles, Issue 3/2023

Genetic Screening of Children with Syndromic Craniosynostosis

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T. Delchev, S. Hadjidekova, Ts. Veleva, S. Bichev, M. Sredkova, I. Boneva, D. Avdjieva-Tzavella


Abstract

Syndromic craniosynostosis (SC) is a genetically determined premature closure of one or more of the cranial sutures, which may result in severe dysmorphism, increased intracranial pressure along with many other clinical manifestations.

Aiming to elucidate the complex genetic etiology of syndromic craniosynostosis, we investigated ninety-nine children, screened systematically with a combination of conventional cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA), array-based comparative genomic hybridization (aCGH) and new generation sequencing (NGS).

Pathological findings were established in 17.9 % of the cases using aCGH, in 10 (10.37%) of the cases using MLPA and in 12 (12.37%) of the children using conventional karyotyping. Five of the patients with normal karyotype carried submicroscopic chromosomal rearrangements.

The systematic genetic evaluation of children with SC revealed a high prevalence of submicroscopic chromosomal rearrangements. Duplications were found to be more common than deletions. This suggests the leading role of those defects in the pathogenesis of syndromic craniosynostosis. The genetic complexity of SC was reaffirmed by the discovery of pathological findings in various chromosomal regions. Certain genes were discussed in conjunction with craniosynostosis.

Key words: craniosynostosis, genetic screening, submicroscopic rearrangements, syndromic

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Address for correspondence:

Department of Clinical genetics, University Children Hospital,
Medical University of Sofia;
11, “Akad. Ivan Geshov” Blvd.
1431, Sofia
Bulgaria
e-mail: trayan_delchev@abv.bg