Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples
Craniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly. Pathogenesis of non-syndromic forms of craniosynostosis is largely unknown. In about 15–30% of cases craniosynostosis occurs in association with other physical an...
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| Format: | Article |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2017.00587/full |
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| author | Marcella Zollino Serena Lattante Daniela Orteschi Silvia Frangella Paolo N. Doronzio Ilaria Contaldo Eugenio Mercuri Giuseppe Marangi |
| author_facet | Marcella Zollino Serena Lattante Daniela Orteschi Silvia Frangella Paolo N. Doronzio Ilaria Contaldo Eugenio Mercuri Giuseppe Marangi |
| author_sort | Marcella Zollino |
| collection | DOAJ |
| description | Craniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly. Pathogenesis of non-syndromic forms of craniosynostosis is largely unknown. In about 15–30% of cases craniosynostosis occurs in association with other physical anomalies and it is referred to as syndromic craniosynostosis. Syndromic forms of craniosynostosis arise from mutations in genes belonging to the Fibroblast Growth Factor Receptor (FGFR) family and the interconnected molecular pathways in most cases. However it can occur in association with other gene variants and with a variety of chromosome abnormalities as well, usually in association with intellectual disability (ID) and additional physical anomalies. Evaluating the molecular properties of the genes undergoing intragenic mutations or copy number variations (CNVs) along with prevalence of craniosynostosis in different conditions and animal models if available, we made an attempt to define two distinct groups of unusual syndromic craniosynostosis, which can reflect direct effects of emerging new candidate genes with roles in suture homeostasis or a non-specific phenotypic manifestation of pleiotropic genes, respectively. RASopathies and 9p23p22.3 deletions are reviewed as examples of conditions in the first group. In particular, we found that craniosynostosis is a relatively common component manifestation of cardio-facio-cutaneous (CFC) syndrome. Chromatinopathies and neurocristopathies are presented as examples of conditions in the second group. We observed that craniosynostosis is uncommon on average in these conditions. It was randomly associated with Kabuki, Koolen-de Vries/KANSL1 haploinsufficiency and Mowat–Wilson syndromes and in KAT6B-related disorders. As an exception, trigonocephaly in Bohring-Opitz syndrome reflects specific molecular properties of the chromatin modifier ASXL1 gene. Surveillance for craniosynostosis in syndromic forms of intellectual disability, as well as ascertainment of genomic CNVs by array-CGH in apparently non-syndromic craniosynostosis is recommended, to allow for improvement of both the clinical outcome of patients and the accurate individual diagnosis. |
| first_indexed | 2024-12-11T06:12:59Z |
| format | Article |
| id | doaj.art-049c0b488b2b46e7be56fb766b243614 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-11T06:12:59Z |
| publishDate | 2017-10-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-049c0b488b2b46e7be56fb766b2436142022-12-22T01:18:04ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2017-10-011110.3389/fnins.2017.00587292634Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as ExamplesMarcella Zollino0Serena Lattante1Daniela Orteschi2Silvia Frangella3Paolo N. Doronzio4Ilaria Contaldo5Eugenio Mercuri6Giuseppe Marangi7Institute of Genomic Medicine, Catholic University, A. Gemelli Hospital, Rome, ItalyInstitute of Genomic Medicine, Catholic University, A. Gemelli Hospital, Rome, ItalyInstitute of Genomic Medicine, Catholic University, A. Gemelli Hospital, Rome, ItalyInstitute of Genomic Medicine, Catholic University, A. Gemelli Hospital, Rome, ItalyInstitute of Genomic Medicine, Catholic University, A. Gemelli Hospital, Rome, ItalyInstitute of Pediatric Neurology, Catholic University, A. Gemelli Hospital, Rome, ItalyInstitute of Pediatric Neurology, Catholic University, A. Gemelli Hospital, Rome, ItalyInstitute of Genomic Medicine, Catholic University, A. Gemelli Hospital, Rome, ItalyCraniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly. Pathogenesis of non-syndromic forms of craniosynostosis is largely unknown. In about 15–30% of cases craniosynostosis occurs in association with other physical anomalies and it is referred to as syndromic craniosynostosis. Syndromic forms of craniosynostosis arise from mutations in genes belonging to the Fibroblast Growth Factor Receptor (FGFR) family and the interconnected molecular pathways in most cases. However it can occur in association with other gene variants and with a variety of chromosome abnormalities as well, usually in association with intellectual disability (ID) and additional physical anomalies. Evaluating the molecular properties of the genes undergoing intragenic mutations or copy number variations (CNVs) along with prevalence of craniosynostosis in different conditions and animal models if available, we made an attempt to define two distinct groups of unusual syndromic craniosynostosis, which can reflect direct effects of emerging new candidate genes with roles in suture homeostasis or a non-specific phenotypic manifestation of pleiotropic genes, respectively. RASopathies and 9p23p22.3 deletions are reviewed as examples of conditions in the first group. In particular, we found that craniosynostosis is a relatively common component manifestation of cardio-facio-cutaneous (CFC) syndrome. Chromatinopathies and neurocristopathies are presented as examples of conditions in the second group. We observed that craniosynostosis is uncommon on average in these conditions. It was randomly associated with Kabuki, Koolen-de Vries/KANSL1 haploinsufficiency and Mowat–Wilson syndromes and in KAT6B-related disorders. As an exception, trigonocephaly in Bohring-Opitz syndrome reflects specific molecular properties of the chromatin modifier ASXL1 gene. Surveillance for craniosynostosis in syndromic forms of intellectual disability, as well as ascertainment of genomic CNVs by array-CGH in apparently non-syndromic craniosynostosis is recommended, to allow for improvement of both the clinical outcome of patients and the accurate individual diagnosis.http://journal.frontiersin.org/article/10.3389/fnins.2017.00587/fullcraniosynostosischromatinopathiesneurocristopathiesRASopathiesKabuki syndromeKoolen-De-Vries syndrome |
| spellingShingle | Marcella Zollino Serena Lattante Daniela Orteschi Silvia Frangella Paolo N. Doronzio Ilaria Contaldo Eugenio Mercuri Giuseppe Marangi Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples Frontiers in Neuroscience craniosynostosis chromatinopathies neurocristopathies RASopathies Kabuki syndrome Koolen-De-Vries syndrome |
| title | Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples |
| title_full | Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples |
| title_fullStr | Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples |
| title_full_unstemmed | Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples |
| title_short | Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples |
| title_sort | syndromic craniosynostosis can define new candidate genes for suture development or result from the non specifc effects of pleiotropic genes rasopathies and chromatinopathies as examples |
| topic | craniosynostosis chromatinopathies neurocristopathies RASopathies Kabuki syndrome Koolen-De-Vries syndrome |
| url | http://journal.frontiersin.org/article/10.3389/fnins.2017.00587/full |
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