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Genetic advances in craniosynostosis.

ABSTRACT: Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, that is, nonsyndromic craniosynostosis (NCS), the genetic, and environmental causes of which remain largely unknown. Recent data suggest that, at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25-30% of patients, craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging, and treatment aspects of NCS is also provided.

SUBMITTER: Lattanzi W

PROVIDER: S-EPMC5397362 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Genetic advances in craniosynostosis.

Lattanzi Wanda W Barba Marta M Di Pietro Lorena L Boyadjiev Simeon A SA

American journal of medical genetics. Part A 20170204 5

Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, that is, nonsyndromic craniosynostosis (NCS), the genetic, and environmental causes of which remain largely unknown. Recent data suggest that, at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25-30% of ...[more]

PMID: 28160402

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Project description:BACKGROUND:Craniosynostosis is a congenital defect that causes one or more sutures on an infant's skull to close earlier than normal. Though both genetic and environmental factors play a role in its pathogenesis, there is no published Indian data to verify this. MATERIALS AND METHODS:In this case-control study, we investigated the association of craniosynostosis with parental age in 50 children with craniosynostosis attending the surgical outpatient department of a tertiary care institution in North India. RESULTS:There was a significant association of craniosynostosis with advanced parental [OR 2.17 (95% CI 1.08 to 4.36)] but not maternal age. Education status of parents also revealed that those having a higher education had an increased risk of having a child with craniosynostosis [maternal education, OR 2.32 (95% CI 1.2 to 4.76); paternal education, OR 2.51 (95% CI 1.21 to 5.0)]. Molecular analysis by sequencing confirmed following amino-acid substitution in different Exons of the FGFR2 gene. Besides these, we found other novel identical mutations in FGFR2 gene in both syndromic and non-syndromic craniosynostoses. CONCLUSION:This is the first epidemiological study in India that provides evidence that, advanced paternal age and higher parental education level might be associated with an increased risk of craniosynostosis. New mutations were identified in cases of both syndromic and non-syndromic craniosynostosis.

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