#616938
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-5 (CSS5) is caused by heterozygous mutation in the SMARCE1 gene (603111) on chromosome 17q21.
Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly (summary by Wieczorek et al., 2013). Patients with SMARCE1 mutations have a wide spectrum of manifestations, including severe to moderate intellectual disability and heart defects (summary by Kosho et al., 2014).
For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Wieczorek et al. (2013) reported a 3-year-old girl (patient K2442) with Coffin-Siris syndrome. She had delayed psychomotor development with intellectual disability and absent speech, poor overall growth with short stature and microcephaly (-4.6 SD), and dysmorphic facial features, including coarse facies, low frontal hairline, thick eyebrows, long eyelashes, flat nasal bridge, broad nose with thick anteverted nares, large mouth, thick lower vermilion, short philtrum, abnormal ears, and sparse scalp hair. Additional features included hypoplasia of the distal phalanges with nail hypoplasia, atrial septal defect, and dextropositio cordis. Brain imaging showed small cerebellum, Dandy-Walker malformation, and abnormal corpus callosum. Wieczorek et al. (2013) reviewed the clinical features in a patient with CSS5 originally reported by Tsurusaki et al. (2012): that patient also had severe intellectual disability, the typical craniofacial gestalt, microcephaly, short stature, feeding difficulties, and congenital heart defects. Both patients had long and slender fingers and all toenails were dystrophic and hypoplastic. One of the patients had seizures.
The heterozygous mutations in the SMARCE1 gene that were identified in patients with CSS5 by Tsurusaki et al. (2012) and Wieczorek et al. (2013) occurred de novo.
In a Japanese patient with CSS5, Tsurusaki et al. (2012) identified a de novo heterozygous missense mutation in the SMARCE1 gene (Y73C; 603111.0001). The mutation was found by exome sequencing. Functional studies of the variant were not performed.
Wieczorek et al. (2013) identified a de novo heterozygous missense mutation affecting the same codon as the mutation identified by Tsurusaki et al. (2012) (Y73S; 603111.0006) in a 3-year-old girl with CSS5. The mutation was found by whole-exome sequencing; functional studies of the variant were not performed. The patient was 1 of 46 individuals with a clinical diagnosis of CSS who underwent sequencing, suggesting that SMARCE1 mutations are not common in this disorder.
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]
Wieczorek, D., Bogershausen, N., Beleggia, F., Steiner-Haldenstatt, S., Pohl, E., Li, Y., Milz, E., Martin, M., Thiele, H., Altmuller, J., Alanay, Y., Kayserili, H., and 44 others. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. Hum. Molec. Genet. 22: 5121-5135, 2013. [PubMed: 23906836, related citations] [Full Text]
ORPHA: 1465; DO: 0112368;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q21.2 | Coffin-Siris syndrome 5 | 616938 | Autosomal dominant | 3 | SMARCE1 | 603111 |
A number sign (#) is used with this entry because of evidence that Coffin-Siris syndrome-5 (CSS5) is caused by heterozygous mutation in the SMARCE1 gene (603111) on chromosome 17q21.
Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly (summary by Wieczorek et al., 2013). Patients with SMARCE1 mutations have a wide spectrum of manifestations, including severe to moderate intellectual disability and heart defects (summary by Kosho et al., 2014).
For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Wieczorek et al. (2013) reported a 3-year-old girl (patient K2442) with Coffin-Siris syndrome. She had delayed psychomotor development with intellectual disability and absent speech, poor overall growth with short stature and microcephaly (-4.6 SD), and dysmorphic facial features, including coarse facies, low frontal hairline, thick eyebrows, long eyelashes, flat nasal bridge, broad nose with thick anteverted nares, large mouth, thick lower vermilion, short philtrum, abnormal ears, and sparse scalp hair. Additional features included hypoplasia of the distal phalanges with nail hypoplasia, atrial septal defect, and dextropositio cordis. Brain imaging showed small cerebellum, Dandy-Walker malformation, and abnormal corpus callosum. Wieczorek et al. (2013) reviewed the clinical features in a patient with CSS5 originally reported by Tsurusaki et al. (2012): that patient also had severe intellectual disability, the typical craniofacial gestalt, microcephaly, short stature, feeding difficulties, and congenital heart defects. Both patients had long and slender fingers and all toenails were dystrophic and hypoplastic. One of the patients had seizures.
The heterozygous mutations in the SMARCE1 gene that were identified in patients with CSS5 by Tsurusaki et al. (2012) and Wieczorek et al. (2013) occurred de novo.
In a Japanese patient with CSS5, Tsurusaki et al. (2012) identified a de novo heterozygous missense mutation in the SMARCE1 gene (Y73C; 603111.0001). The mutation was found by exome sequencing. Functional studies of the variant were not performed.
Wieczorek et al. (2013) identified a de novo heterozygous missense mutation affecting the same codon as the mutation identified by Tsurusaki et al. (2012) (Y73S; 603111.0006) in a 3-year-old girl with CSS5. The mutation was found by whole-exome sequencing; functional studies of the variant were not performed. The patient was 1 of 46 individuals with a clinical diagnosis of CSS who underwent sequencing, suggesting that SMARCE1 mutations are not common in this disorder.
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]
Wieczorek, D., Bogershausen, N., Beleggia, F., Steiner-Haldenstatt, S., Pohl, E., Li, Y., Milz, E., Martin, M., Thiele, H., Altmuller, J., Alanay, Y., Kayserili, H., and 44 others. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. Hum. Molec. Genet. 22: 5121-5135, 2013. [PubMed: 23906836] [Full Text: https://doi.org/10.1093/hmg/ddt366]
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