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. The considerable risk of complications along with significant incidence makes these cranial deformations an important medical problem. Despite the efforts to clarify the pathogenesis of SC in recent years, its genetic aspects remain largely unknown.
Aiming to elucidate the complex genetic etiology of syndromic craniosynostosis, we conducted an investigation of 39 children, screened systematically with a combination of conventional cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridisation (aCGH).
Pathological findings were established in 15.3% (6/39) of the cases using aCGH, in 7.7% (3/39) using MLPA and 2.5% (1/39) using conventional karyotyping. About 12.8% (5/39) of the patients with normal karyotype carried submicroscopic chromosomal rearrangements. Duplications were found to be more common than deletions.
Conclusion: The systematic genetic evaluation of children with SC revealed a high prevalence of submicrosopic chromosomal rearrangements (most commonly duplications and gain-of-function variations). 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.