Genetic basis of single-suture synostoses: genes, chromosomes and clinical implications

Lattanzi, Wanda; Bukvić, Nenad; Barba, Marta; Tamburrini, Gianpiero; Bernardini, Camilla; Michetti, Fabrizio; Rocco, Concezio Di

doi:10.1007/s00381-012-1781-1

Cited by 56 publications

(26 citation statements)

References 75 publications

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“…In conclusion, most of the features related to TCF12 mutations resemble those of SCS 8 with a large clinical spectrum. The close relationship between TCF12 and TWIST1 raises the question whether TCF12 mutations could be responsible for other types of abnormal sutures, as sometimes occurs in SCS.…”

Section: Discussionmentioning

confidence: 83%

Clinical spectrum and outcomes in families with coronal synostosis and TCF12 mutations

et al. 2014

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TCF12 mutations have been reported very recently in coronal synostosis. We report several cases of familial coronal synostosis among four families harbouring novel TCF12 mutations. We observed a broad interfamilial phenotypic spectrum with features overlapping with the Saethre-Chotzen syndrome. TCF12 molecular testing should be considered in patients with unilateral-or bilateral-coronal synostosis associated or not with syndactyly, after having excluded mutations in the TWIST1 gene and the p.Pro250Arg mutation in INTRODUCTIONThe aetiology of several cases of non-syndromic coronal craniosynostosis without abnormalities of the extremities remained genetically unexplained until fibroblast growth factor receptor 3 (FGFR3) and TWIST1 mutations were characterised. The p.Pro250Arg (c.749C4G) mutation in FGFR3, which is associated with Muenke syndrome [MIM#602849], 1 is identified in about 70% of familial non-syndromic coronal synostosis. 2 This syndrome, in its complete phenotype, includes unilateral (plagiocephaly) or bilateral (brachycephaly) premature closure of the coronal sutures, hearing loss, broad toes, and carpal and tarsal fusions. The phenotype is however, variable, including non-penetrance, isolated craniosynostosis and features which overlap with other craniosynostosis syndromes (eg Crouzon syndrome, Saethre-Chotzen syndrome (SCS) and cloverleaf skull). 3,4 TWIST1 mutations, which are typically associated with SCS syndrome may also be identified in up to 46% cases of brachycephaly. 3 SCS typically presents with coronal synostosis, small ear with prominent crus, ptosis, syndactyly, and broad thumb and/or broad hallux. However, SCS also displays phenotypic variability depending on the type of mutation involved. 5 The TCF12 gene, which encodes a basic helix-loop-helix (bHLH) transcription factor, was recently identified by exome sequencing in cases displaying premature fusion of the coronal sutures. 6 Therefore, we tried to detect TCF12 mutations in five families with coronal synostosis, after negative prior screening for FGFR3 or TWIST1 mutations, and found four positive families. We then reviewed the clinical manifestations and outcomes in these families, and further discussed their phenotype/genotype correlations.

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Section: Discussionmentioning

confidence: 83%

Clinical spectrum and outcomes in families with coronal synostosis and TCF12 mutations

et al. 2014

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“…Single-suture synostosis is the most common craniofacial malformation, and the most frequently involved sutures are sagittal, coronal, metopic and lambdoid, in order of occurrence, although recent publications show a rise in the incidence of metopic suture synostosis during the last years due to either genetic or epigenetic and environmental factors, which are still largely obscure [17,18]. The findings of the present study agree with these reports, with metopic synostosis as frequent as sagittal synostosis in single-suture cases (table 3).…”

Section: Discussionmentioning

confidence: 99%

The ‘Brain Shadowing Sign': A Novel Marker of Fetal Craniosynostosis

Haratz

Leibovitz²,

Svirsky

et al. 2016

Fetal Diagn Ther

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Introduction: The prenatal diagnosis of fetal craniosynostosis is challenging, especially in single-suture cases. When sutures are obliterated, sound waves fail to penetrate the cortical bone, creating an evident acoustic shadow on the underlying brain. The objective of this study was to evaluate the yield of the ‘brain shadowing sign' (BSS) as a novel sonographic marker for craniosynostosis. Subjects and Methods: Patients with an antenatal diagnosis of fetal craniosynostosis (cases) and healthy controls paired for gestational age were enrolled in this retrospective case-control study. Two-dimensional scans were assessed by three examiners for the presence of the BSS and additional fetal findings. Results: The BSS was clearly depicted in all 24 cases on the first analysis and in 22 cases on the second analysis. No fetus from the control group (n = 48) presented the BSS in any of the analyses. Fifteen cases had isolated craniosynostosis and 9 were syndromic (Apert, Saethre-Chotzen and craniofrontonasal syndromes), which were diagnosed significantly earlier due to additional malformations. Discussion: The BSS is a novel sonographic marker of craniosynostosis which can be used to increase the diagnostic rate of this rare condition and does not require the use of high-definition three-dimensional transducers to be depicted.

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“…Both DLX5 and DLX6 are indeed required for NC-derived facial morphogenesis (Gitton et al, 2011) FGFRs are among the main craniosynostosis-associated genes. In particular, gain-of-function mutations in FGFR2 are typically associated to Apert (OMIM#101200) and Crouzon (OMIM#123500) syndromes, while both FGFR1 and FGFR2 are found mutated in Pfeiffer syndrome (OMIM#101600) (Lattanzi et al, 2012). All these syndromic craniosynostoses occasionally present with variable degree of ASD-like mental retardation (Morey-Canellas et al, 2003).…”

Section: Asd and The Genetics Of The Domestication Syndromementioning

confidence: 99%

Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain

2016

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Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesized to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioral levels. We also discuss many ASD candidates represented among the genes known to be involved in the “domestication syndrome” (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behavior of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the “domestication syndrome” and, ultimately, from the normal functioning of the neural crest.

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Genetic basis of single-suture synostoses: genes, chromosomes and clinical implications

Cited by 56 publications

References 75 publications

Clinical spectrum and outcomes in families with coronal synostosis and TCF12 mutations

Clinical spectrum and outcomes in families with coronal synostosis and TCF12 mutations

The ‘Brain Shadowing Sign': A Novel Marker of Fetal Craniosynostosis

Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain

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