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| Rare syndromic craniosynostosis or isolated multisuture synostosis v4.97 | SMAD3 | Achchuthan Shanmugasundram Publications for gene: SMAD3 were set to 20301312; 29392890; 31569402; 32935439 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v4.96 | SMAD3 | Achchuthan Shanmugasundram edited their review of gene: SMAD3: Changed publications to: 29392890, 31569402, 32935439, 36980886; Changed phenotypes to: Loeys-Dietz syndrome 3, OMIM:613795 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v4.96 | SMAD3 |
Achchuthan Shanmugasundram changed review comment from: PMID:29392890 - It has been reviewed in this publication that craniosynostosis has only been reported once in a SMAD3 patient. But, no reference was given. PMID:31569402 - Dolichocephaly has been reported in patients. However, it is not clear whether craniosynostosis has been present in these cases. PMID:32935439 - One case of LDS with biallelic variants presented with craniosynostosis. PMID:36980886 - one craniosynostosi case with splicing variant in SMAD3 from the cohort of 617 individuals. This gene has been associated with LDS in OMIM (MIM #613795) and Gene2Phenotype (with 'definitive' rating in DD panel). However, craniosynostosis was not reported as part of phenotypes in OMIM.; to: PMID:29392890 - It has been reviewed in this publication that craniosynostosis has only been reported once in a SMAD3 patient. But, no reference was given. PMID:31569402 - Dolichocephaly has been reported in patients. However, it is not clear whether craniosynostosis has been present in these cases. PMID:32935439 - One case of LDS with biallelic variants presented with craniosynostosis. PMID:36980886 - one craniosynostosi case with splicing variant in SMAD3 from the cohort of 617 individuals. This gene has been associated with LDS in OMIM (MIM #613795) and Gene2Phenotype (with 'definitive' rating in DD panel). However, craniosynostosis was not reported as part of this phenotype in OMIM. |
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| Rare syndromic craniosynostosis or isolated multisuture synostosis v4.96 | SMAD3 | Achchuthan Shanmugasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v3.4 | SMAD3 | Rebecca Tooze reviewed gene: SMAD3: Rating: ; Mode of pathogenicity: None; Publications: https://doi.org/10.3390/genes14030615; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.58 | SMAD3 | Eleanor Williams Classified gene: SMAD3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.58 | SMAD3 | Eleanor Williams Added comment: Comment on list classification: On advice from Genomics England clinical team, promoting this gene from grey to amber. The number of cases with a craniosynostosis phenotype is borderline so rating as amber for now. Only 1 biallelic case reported so far so keeping the mode of inheritance as monoallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.58 | SMAD3 | Eleanor Williams Gene: smad3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.57 | SMAD3 | Eleanor Williams Phenotypes for gene: SMAD3 were changed from Loeys-Dietz syndrome 3, MIM# 613795 to Loeys-Dietz syndrome 3, OMIM:613795 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.56 | SMAD3 | Eleanor Williams Publications for gene: SMAD3 were set to 20301312; 29392890 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.40 | SMAD3 |
Eleanor Williams changed review comment from: Associated with Loeys-Dietz syndrome 3 #613795 (AD) in OMIM but craniosynostosis not listed as a clinical feature. PMID: 20301312 - Loeys and Dietz (2008 updated 2018) - Gene Reviews - states that in severe presentation, craniofacial anomalies in individuals with LDS are characterized by widely spaced eyes and craniosynostosis. PMID: 29392890 - Schepers et al 2018 - review of genes/variants associated with Loeys-Dietz syndrome. Table 5 indicates that only SMAD3 variants are associated with craniosynostosis and text says that "craniosynostosis has only been reported once in a SMAD3 patient" but no reference is given. Looking at reported phenotypes for LDS patients with a SMAD3 variant: PMID: 31569402 - Camerota et al 2019 - report 4 families with LDS and SMAD3 variants. 3/9 individuals from 3 different Italian families presented with dolichocephaly among other phenotypes. 4 families reported with SMAD3 variants in total, each with a different likely causative variant. PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. Dolichocephaly in the proband is mentioned.; to: Associated with Loeys-Dietz syndrome 3 #613795 (AD) in OMIM but craniosynostosis not listed as a clinical feature. PMID: 20301312 - Loeys and Dietz (2008 updated 2018) - Gene Reviews - states that in severe presentation, craniofacial anomalies in individuals with LDS are characterized by widely spaced eyes and craniosynostosis. PMID: 29392890 - Schepers et al 2018 - review of genes/variants associated with Loeys-Dietz syndrome. Table 5 indicates that only SMAD3 variants are associated with craniosynostosis and text says that "craniosynostosis has only been reported once in a SMAD3 patient" but no reference is given. Looking at reported phenotypes for LDS patients with a SMAD3 variant and craniosynostosis phenotype: PMID: 31569402 - Camerota et al 2019 - report 4 families with LDS and SMAD3 variants. 3/9 individuals from 3 different Italian families presented with dolichocephaly among other phenotypes. 4 families reported with SMAD3 variants in total, each with a different likely causative variant. PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. Dolichocephaly in the proband is mentioned. |
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| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.40 | SMAD3 | Eleanor Williams reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 29392890, 31569402, 32935439; Phenotypes: Loeys-Dietz syndrome 3 OMIM:613795; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.9 | SMAD3 |
Zornitza Stark gene: SMAD3 was added gene: SMAD3 was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMAD3 were set to 20301312; 29392890 Phenotypes for gene: SMAD3 were set to Loeys-Dietz syndrome 3, MIM# 613795 Review for gene: SMAD3 was set to GREEN Added comment: Craniosynostosis is a feature of LDS. Sources: Expert list |
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