Craniosynostosis and Chromosomal Alterations

Passos‐Bueno, Maria Rita; Fanganiello, Roberto Dalto; Jehee, Fernanda Sarquis

doi:10.1159/000319987

Cited by 7 publications

(1 citation statement)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Along similar lines, craniosynostosis has been documented in association with many chromosomal abnormalities, 16 but usually only a minority of those with similar chromosome imbalances actually develop the condition, suggesting non-specific mechanisms through poor brain growth and/or transduction of strain. 17 The second factor, the intrinsic property of the suture itself, is the focus of this review.…”

Section: Introductionmentioning

confidence: 90%

A Genetic-Pathophysiological Framework for Craniosynostosis

Twigg

Wilkie

2015

The American Journal of Human Genetics

226

261

View full text Add to dashboard Cite

Craniosynostosis, the premature fusion of one or more cranial sutures of the skull, provides a paradigm for investigating the interplay of genetic and environmental factors leading to malformation. Over the past 20 years molecular genetic techniques have provided a new approach to dissect the underlying causes; success has mostly come from investigation of clinical samples, and recent advances in high-throughput DNA sequencing have dramatically enhanced the study of the human as the preferred "model organism." In parallel, however, we need a pathogenetic classification to describe the pathways and processes that lead to cranial suture fusion. Given the prenatal onset of most craniosynostosis, investigation of mechanisms requires more conventional model organisms; principally the mouse, because of similarities in cranial suture development. We present a framework for classifying genetic causes of craniosynostosis based on current understanding of cranial suture biology and molecular and developmental pathogenesis. Of note, few pathologies result from complete loss of gene function. Instead, biochemical mechanisms involving haploinsufficiency, dominant gain-of-function and recessive hypomorphic mutations, and an unusual X-linked cellular interference process have all been implicated. Although few of the genes involved could have been predicted based on expression patterns alone (because the genes play much wider roles in embryonic development or cellular homeostasis), we argue that they fit into a limited number of functional modules active at different stages of cranial suture development. This provides a useful approach both when defining the potential role of new candidate genes in craniosynostosis and, potentially, for devising pharmacological approaches to therapy.

show abstract

Section: Introductionmentioning

confidence: 90%