Format

Send to

Choose Destination
Curr Opin Pediatr. 2017 Dec;29(6):622-628. doi: 10.1097/MOP.0000000000000542.

Clinical genetics of craniosynostosis.

Author information

1
aClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital bOxford Centre for Genomic Medicine, Nuffield Orthopaedic Centre cCraniofacial Unit, John Radcliffe Hospital, Headington, Oxford, UK.

Abstract

PURPOSE OF REVIEW:

When providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic discoveries from next-generation sequencing have impacted on the clinical genetic evaluation of craniosynostosis.

RECENT FINDINGS:

Survey of a 13-year birth cohort of patients treated at a single craniofacial unit demonstrates that a genetic cause of craniosynostosis can be identified in one quarter of cases. The substantial contributions of mutations in two genes, TCF12 and ERF, is confirmed. Important recent discoveries are mutations of CDC45 and SMO in specific craniosynostosis syndromes, and of SMAD6 in nonsyndromic midline synostosis. The added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted.

SUMMARY:

Strategies to optimize clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed. In addition to improved genetic counseling, recent discoveries spotlight the important roles of signaling through the bone morphogenetic protein and hedgehog pathways in cranial suture biogenesis, as well as a key requirement for adequate cell division in suture maintenance.

PMID:
28914635
PMCID:
PMC5681249
DOI:
10.1097/MOP.0000000000000542
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center