Details of Disease

General Information of Disease (ID: DIS8L03H)

• Disease Name: Coffin-Siris syndrome
• Synonyms: intellectual disability with absent fifth fingernail and terminal phalanx; CSS; fifth digit syndrome; dwarfism-onychodysplasia; short stature-onychodysplasia.; Coffin-Siris syndrome
• Definition: Coffin-Siris syndrome (CSS) is a rare congenital multi-systemic genetic disorder characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth digit, developmental delay, intellectual disability, coarse facial features, and other variable clinical manifestations.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISYKSRF: Genetic disease
  DIS5PU87: Skeletal system disorder
  DISDOXWZ: Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
  DIS8L03H: Coffin-Siris syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0015452
  MESH ID: C536436
  UMLS CUI: C0265338
  MedGen ID: 75565
  Orphanet ID: 1465
  SNOMED CT ID: 10007009

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SDHD	TTVH9W8	Strong	Genetic Variation	[1]
SMARCA4	TTVQEZS	Definitive	Autosomal dominant	[2]

This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BANF1	OTP7Z38L	Limited	Genetic Variation	[3]
SMARCD1	OTHFFT6G	Supportive	Autosomal dominant	[4]
SMARCE1	OTAX4ITH	Supportive	Autosomal dominant	[5]
SOX11	OT4LG7LA	Supportive	Autosomal dominant	[6]
SOX4	OTSS40SS	Supportive	Autosomal dominant	[7]
SMARCA1	OT0Y6PTU	moderate	Genetic Variation	[8]
CCL26	OT2B7HR9	Strong	Genetic Variation	[9]
CPED1	OTJJPZOZ	Strong	Genetic Variation	[10]
FAM3C	OTBR6U9G	Strong	Genetic Variation	[10]
IL17RB	OT0KDNSF	Strong	Biomarker	[11]
NIPBL	OTF6OOLU	Strong	Genetic Variation	[12]
PHF6	OT8DXI40	Strong	Biomarker	[13]
SDHB	OTRE1M1T	Strong	Biomarker	[1]
SDHC	OTC8G2MX	Strong	Genetic Variation	[1]
SMARCA2	OTSGJ8SV	Strong	Genetic Variation	[14]
SMARCAL1	OTTKXLUZ	Strong	Genetic Variation	[15]
ARID1A	OTRWDV3P	Definitive	Autosomal dominant	[2]
ARID1B	OTILK3Q7	Definitive	Autosomal dominant	[2]
ARID2	OTIRJXWM	Definitive	Autosomal dominant	[2]
DPF2	OTL0JH2C	Definitive	Autosomal dominant	[2]
SMARCA4	OT68WOPQ	Definitive	Autosomal dominant	[2]
SMARCB1	OT2LP7LJ	Definitive	Autosomal dominant	[2]
SMARCC2	OTC5SNMZ	Definitive	Autosomal dominant	[2]

References

• [1] Succinate dehydrogenase (SDH) deficiency, Carney triad and the epigenome.Mol Cell Endocrinol. 2018 Jul 5;469:107-111. doi: 10.1016/j.mce.2017.07.018. Epub 2017 Jul 21.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Expanding the phenotypic spectrum associated with DPF2: A new case report.Am J Med Genet A. 2019 Aug;179(8):1637-1641. doi: 10.1002/ajmg.a.61262. Epub 2019 Jun 17.
• [4] A Syndromic Neurodevelopmental Disorder Caused by Mutations in SMARCD1, a Core SWI/SNF Subunit Needed for Context-Dependent Neuronal Gene Regulation in Flies. Am J Hum Genet. 2019 Apr 4;104(4):596-610. doi: 10.1016/j.ajhg.2019.02.001. Epub 2019 Mar 14.
• [5] Coffin-Siris Syndrome. 2013 Apr 4 [updated 2021 Aug 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [6] De novo SOX11 mutations cause Coffin-Siris syndrome. Nat Commun. 2014 Jun 2;5:4011. doi: 10.1038/ncomms5011.
• [7] Extremely Low Prevalence of Takotsubo Cardiomyopathy and Transient Cardiac Dysfunction in Stroke Patients With T-wave Abnormalities. Am J Cardiol. 2019 Mar 15;123(6):1009. doi: 10.1016/j.amjcard.2019.01.001. Epub 2019 Jan 9.
• [8] Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients.Eur J Med Genet. 2019 Jan;62(1):27-34. doi: 10.1016/j.ejmg.2018.04.014. Epub 2018 Apr 23.
• [9] Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study.Rheumatology (Oxford). 2011 Oct;50(10):1823-7. doi: 10.1093/rheumatology/keq445. Epub 2011 Jan 25.
• [10] Duplication of C7orf58, WNT16 and FAM3C in an obese female with a t(7;22)(q32.1;q11.2) chromosomal translocation and clinical features resembling Coffin-Siris Syndrome.PLoS One. 2012;7(12):e52353. doi: 10.1371/journal.pone.0052353. Epub 2012 Dec 27.
• [11] Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome.Blood. 2010 Nov 25;116(22):4523-31. doi: 10.1182/blood-2010-02-267542. Epub 2010 Aug 20.
• [12] Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes.Hum Genet. 2017 Mar;136(3):307-320. doi: 10.1007/s00439-017-1758-y. Epub 2017 Jan 24.
• [13] Females with de novo aberrations in PHF6: clinical overlap of Borjeson-Forssman-Lehmann with Coffin-Siris syndrome. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):290-301. doi: 10.1002/ajmg.c.31408. Epub 2014 Aug 5.
• [14] Patient with anomalous skin pigmentation expands the phenotype of ARID2 loss-of-function disorder, a SWI/SNF-related intellectual disability.Am J Med Genet A. 2019 May;179(5):808-812. doi: 10.1002/ajmg.a.61075. Epub 2019 Mar 5.
• [15] Regulation of ATM and ATR by SMARCAL1 and BRG1.Biochim Biophys Acta Gene Regul Mech. 2018 Dec;1861(12):1076-1092. doi: 10.1016/j.bbagrm.2018.10.004. Epub 2018 Oct 11.