Genetic and Epigenetic Influences of Twins on the Pathogenesis of Craniosynostosis

Lakin, Gregory E.; Sinkin, Jeremy C.; Chen, Rui; Koltz, Peter F.; Girotto, John A.

doi:10.1097/prs.0b013e31824422a8

Cited by 32 publications

(19 citation statements)

References 30 publications

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“…The present study describes the occurrence of isolated craniosynostosis with opposite directed impact on craniofacial growth (scaphocephaly versus oxycephaly) in monozygotic twins and supports the hypothesis proposed previously in other studies (Lajeunie et al, 2005;Butzelaar et al, 2009;Johnson and Wilkie, 2011;Lakin et al, 2012) that a combination of predisposition (genetic factors) and an environmental component (i.e. constraint secondary to twin pregnancy or large fetus) may cause isolated craniosynostosis.…”

Section: Discussionsupporting

confidence: 87%

“…A recent meta-analysis by Lakin et al (2012) reviewing the literature of monozygotic and dizygotic twins with isolated craniosynostosis has concluded that craniosynostosis likely results from a combination of genetic and environmental factors. The present study describes the occurrence of isolated craniosynostosis with opposite directed impact on craniofacial growth (scaphocephaly versus oxycephaly) in monozygotic twins and supports the hypothesis proposed previously in other studies (Lajeunie et al, 2005;Butzelaar et al, 2009;Johnson and Wilkie, 2011;Lakin et al, 2012) that a combination of predisposition (genetic factors) and an environmental component (i.e.…”

Section: Discussionmentioning

confidence: 98%

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Monozygotic twins presenting with isolated sagittal and bicoronal synostosis, respectively

Hove

Dunø

Larsen

et al. 2016

Clinical Dysmorphology

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 98%

Monozygotic twins presenting with isolated sagittal and bicoronal synostosis, respectively

Hove

Dunø

Larsen

et al. 2016

Clinical Dysmorphology

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“…Although an adverse intrauterine environment may contribute substantially to the origin of many cases of craniosynostosis [11–13], this is difficult to prove in the individual patient [14]. Overall, only 2.4% of cases were attributed to a likely secondary cause in the Oxford series.…”

Section: A Current Benchmark For Diagnosismentioning

confidence: 99%

Clinical genetics of craniosynostosis

Wilkie

Johnson²,

Wall³

2017

Current Opinion in Pediatrics

154

169

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Purpose of review When providing accurate clinical diagnosis and genetic counselling 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 non-syndromic midline synostosis. The added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted. Summary Strategies to optimise clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed. As well as improved genetic counselling, recent discoveries spotlight the important roles of signalling 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.

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“…Prenatal risk factors, such as maternal thyroid disorders, gestational diabetes, drug use, malnutrition, virus infectious, intrauterine constraint, twin gestation, premature delivery, are associated with craniosynostosis and likely increase the susceptibility in an already genetically predisposed infant [7,[11][12][13][14]. Monochorionic (MC) twins provide exceptional chances to decipher the interplay among genetic and environment in uences in the pathogenesis of premature suture fusion [34]. In our study, the mother of monochorionic twins suffered the majority of risk factors prenatally, however, only the infant with breech presentation and intrauterine growth restriction experienced sagittal craniosynostosis.…”

Section: Discussionmentioning

confidence: 99%

A novel AXIN2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a monochorionic diamniotic twin family

Xu¹,

Yan²,

Song³

et al. 2020

Preprint

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Background: Craniosynostosis, the premature fusion of one or more cranial sutures, affects approximately 1 in every 2000-2500 live births. The etiology of sagittal craniosynostosis, the most prevalent form of isolated craniosynostosis, involves interplay between genetic and environmental insults, such as perinatal risk factors. However, the detailed information still remains largely unknown. Methods: The proband, a female monochorionic twin diagnosed with sagittal craniosynostosis, as well as her healthy twin sister and parents, were enrolled in our study. The obstetric medical records were retrospectively reviewed. Genetic cause was investigated by whole exome sequencing (WES) and further confirmed by Sanger sequencing.Results: We identified a novel heterozygous mutation of AXIN2 (c.1181G>A) in monochorionic twins and their father. However, only the proband presented sagittal craniosynostosis. This mutation results in the replacement of Arg at residue 394 by His (p.R394H). Arg 394 is located at the GSK3β binding domain of the AXIN2 protein, which is highly conserved across species. The obstetric medical records revealed that the proband had additional persistent breech presentation and intrauterine growth restriction, except for the perinatal risk factors shared by the twins.Conclusions: Based on the role of AXIN2 in craniosynostosis development and deleterious prediction in silico of AXIN2 (c.1181G>A: p.R394H), we speculate that this particular mutation confers susceptibility to sagittal craniosynostosis, while extra environmental insults are also involved in the pathogenesis of this case. Our findings provide a new evidence for the gene-environment interplay in understanding pathogenesis of craniosynostosis.

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Genetic and Epigenetic Influences of Twins on the Pathogenesis of Craniosynostosis

Abstract: Risk, IV.

Cited by 32 publications

References 30 publications

Monozygotic twins presenting with isolated sagittal and bicoronal synostosis, respectively

Monozygotic twins presenting with isolated sagittal and bicoronal synostosis, respectively

Clinical genetics of craniosynostosis

A novel AXIN2 mutation and perinatal risk factors contribute to sagittal craniosynostosis: evidence from a monochorionic diamniotic twin family

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