#614609
Table of Contents
| Location | Phenotype | Inheritance |
Phenotype mapping key |
Phenotype MIM number |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p36.11 | Coffin-Siris syndrome 2 | AD | 3 | 614607 | ARID1A | 603024 |
| 2p25.2 | Intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism | AD | 3 | 615866 | SOX11 | 600898 |
| 6p22.3 | Coffin-Siris syndrome 10 | AD | 3 | 618506 | SOX4 | 184430 |
| 6q25.3 | Coffin-Siris syndrome 1 | AD | 3 | 135900 | ARID1B | 614556 |
| 11q13.1 | Coffin-Siris syndrome 7 | AD | 3 | 618027 | DPF2 | 601671 |
| 12q12 | Coffin-Siris syndrome 6 | AD | 3 | 617808 | ARID2 | 609539 |
| 12q13.12 | Coffin-Siris syndrome 11 | AD | 3 | 618779 | SMARCD1 | 601735 |
| 12q13.2 | Coffin-Siris syndrome 8 | AD | 3 | 618362 | SMARCC2 | 601734 |
| 17q21.2 | Coffin-Siris syndrome 5 | AD | 3 | 616938 | SMARCE1 | 603111 |
| 19p13.2 | Coffin-Siris syndrome 4 | AD | 3 | 614609 | SMARCA4 | 603254 |
| 19q13.33 | Coffin-Siris syndrome 12 | AD | 3 | 619325 | BICRA | 605690 |
| 22q11.23 | Coffin-Siris syndrome 3 | AD | 3 | 614608 | SMARCB1 | 601607 |
A number sign (#) is used with this entry because of evidence that Coffin-Siris syndrome-4 (CSS4) is caused by heterozygous mutation in the SMARCA4 gene (603254) on chromosome 19p13. The SMARCA4 gene is one of several genes encoding subunits of the SWI/SNF complex, also known as the BAF complex, which functions as a chromatin remodeling factor.
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with SMARCA4 mutations may have less coarse craniofacial appearances and fewer behavioral abnormalities than Coffin-Siris patients with mutations in other genes (summary by Kosho et al., 2014).
For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Tsurusaki et al. (2012) described 6 patients with Coffin-Siris syndrome. All 6 had developmental delay, 4 had hypotonia, and 4 of 5 examined had microcephaly. Two of the 6 had seizures, and 1 of 5 examined had a Dandy-Walker malformation. Five of the 6 had vision problems and half had hearing problems; all had absent or hypoplastic fifth fingernails or toenails; all were hirsute; and 3 of the 6 had sparse scalp hair. All had thick eyebrows and long eyelashes.
In 6 patients with Coffin-Siris syndrome, Tsurusaki et al. (2012) identified an in-frame deletion (603254.0002) and 5 different missense mutations (603254.0003-603254.0007) in the SMARCA4 gene. In 5 cases the mutation was shown to have occurred de novo; in the sixth, parental DNA was not available.
Kosho, T., Okamoto, N., Coffin-Siris Syndrome International Collaborators. Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am. J. Med. Genet. 166C: 262-275, 2014. [PubMed: 25168959, related citations] [Full Text]
Tsurusaki, Y., Okamoto, N., Ohashi, H., Kosho, T., Imai, Y., Hibi-Ko, Y., Kaname, T., Naritomi, K., Kawame, H., Wakui, K., Fukushima, Y., Homma, T., and 19 others. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nature Genet. 44: 376-378, 2012. [PubMed: 22426308, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 1465; DO: 0070046;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.2 | Coffin-Siris syndrome 4 | 614609 | Autosomal dominant | 3 | SMARCA4 | 603254 |
A number sign (#) is used with this entry because of evidence that Coffin-Siris syndrome-4 (CSS4) is caused by heterozygous mutation in the SMARCA4 gene (603254) on chromosome 19p13. The SMARCA4 gene is one of several genes encoding subunits of the SWI/SNF complex, also known as the BAF complex, which functions as a chromatin remodeling factor.
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with SMARCA4 mutations may have less coarse craniofacial appearances and fewer behavioral abnormalities than Coffin-Siris patients with mutations in other genes (summary by Kosho et al., 2014).
For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Tsurusaki et al. (2012) described 6 patients with Coffin-Siris syndrome. All 6 had developmental delay, 4 had hypotonia, and 4 of 5 examined had microcephaly. Two of the 6 had seizures, and 1 of 5 examined had a Dandy-Walker malformation. Five of the 6 had vision problems and half had hearing problems; all had absent or hypoplastic fifth fingernails or toenails; all were hirsute; and 3 of the 6 had sparse scalp hair. All had thick eyebrows and long eyelashes.
In 6 patients with Coffin-Siris syndrome, Tsurusaki et al. (2012) identified an in-frame deletion (603254.0002) and 5 different missense mutations (603254.0003-603254.0007) in the SMARCA4 gene. In 5 cases the mutation was shown to have occurred de novo; in the sixth, parental DNA was not available.
Kosho, T., Okamoto, N., Coffin-Siris Syndrome International Collaborators. Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am. J. Med. Genet. 166C: 262-275, 2014. [PubMed: 25168959] [Full Text: https://doi.org/10.1002/ajmg.c.31407]
Tsurusaki, Y., Okamoto, N., Ohashi, H., Kosho, T., Imai, Y., Hibi-Ko, Y., Kaname, T., Naritomi, K., Kawame, H., Wakui, K., Fukushima, Y., Homma, T., and 19 others. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nature Genet. 44: 376-378, 2012. [PubMed: 22426308] [Full Text: https://doi.org/10.1038/ng.2219]
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