Coffin-Siris syndrome is a congenital condition that occurs as a result of a new or an inherited genetic mutation that follows an autosomal dominant pattern. Some of the features commonly associated with this condition include intellectual disability, developmental challenges, dysmorphic facial structures, and hypoplastic fingernails or toenails of the fifth digits.
Coffin-Siris syndrome (CSS) is an uncommon congenital disease that affects many systems in the body. It presents with a wide range of clinical features.
CSS can be caused by heterozygous genetic mutations in any of the genes that have been linked to the condition. Examples include the genes ARID1B (AT-rich interactive domain-containing protein 1B), and SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) . Although some mutations are inherited (according to an autosomal dominant pattern), many cases of CSS occur de novo .
Regularly reported features include intellectual and developmental impairment with varying severity, dysmorphic facial features, and dysplastic nails on the fifth digit. These are considered the major features of CSS. Typical CSS facies exhibit a wide mouth and nasal bridge, everted lips, downward slanting eyes, and thick eyebrows. The more frequently observed minor features of CSS include failure to thrive, short stature, microcephaly, and sparse scalp hair. In contrast, there may be excessive hair growth, usually involving the torso, face and upper limbs.
In the central nervous system (CNS), manifestations of CSS include seizures, Dandy-Walker malformation, hypotonia, and other anatomical abnormalities. Furthermore, patients diagnosed with CSS are also prone to abnormalities in other systems, such as the cardiovascular system (CVS). A few of the known CVS manifestations are exemplified by tetralogy of Fallot (ToF), atrial septal defect (ASD) or ventricular septal defect (VSD) . CSS may cause hearing problems, as well as visual impairment. Ocular abnormalities include cataracts and strabismus.
Various other minor features have been described, such as single palmar creases, low set ears, renal malformations, and gastrointestinal and skeletal abnormalities  . The latter may appear as spinal abnormalities such as scoliosis, often seen during childhood.
Individuals affected by CSS have a higher incidence of infections, compared with the general population, due to a higher susceptibility. Infections can occur in numerous parts of the body, including the respiratory and urogenital systems  .
Entire Body System
- Single Transverse Palmar Crease
transverse palmar creases 0007598 Cataract Clouding of the lens of the eye Cloudy lens [ more ] 0000518 Cleft palate Cleft roof of mouth 0000175 Congenital diaphragmatic hernia 0000776 Coxa valga 0002673 Cutis marmorata 0000965 Ectopic kidney Abnormal [rarediseases.info.nih.gov]
Jaw & Teeth
- Decrease in Height
[…] body height Small stature [ more ] 0004322 Slow-growing hair Slow growing hair Slow rate of hair growth Slow speed of hair growth [ more ] 0002217 Thick eyebrow Bushy eyebrows Dense eyebrow Heavy eyebrows Prominent eyebrows Thick eyebrows [ more ] 0000574 [rarediseases.info.nih.gov]
Face, Head & Neck
Coffin-Siris syndrome may be diagnosed clinically through the assessment of presenting signs and symptoms. Although the type of feature presenting, whether major or minor, is important when considering the diagnosis of CCS, there is no set of standard diagnostic criteria for the condition . Hypoplasia or aplasia of the fifth digit nail and distal phalanx may be absent, and is not necessary for the diagnosis of CSS to be made. Genetic testing is used to confirm the diagnosis; however, prenatal detection of the condition is limited by the presence of spontaneous cases .
- Wieczorek D, Bögershausen N, Beleggia F, et al. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. Hum Mol Genet. 2013;22(25):5121-5135.
- Vergano SS, Santen G, Wieczorek D, Wollnik B, Matsumoto N, Deardorff MA. Coffin-Siris Syndrome. GeneReviews. http://www.ncbi.nlm.nih.gov/books/NBK131811/. Published July 11, 2013. Accessed June 21, 2018.
- Vergano SS, Deardorff MA. Clinical features, diagnostic criteria, and management of Coffin-Siris syndrome. Am J Med Genet C Semin Med Genet. 2014;166C(3):252-256.
- Hoyer J, Ekici AB, Endele S, et al. Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. Am J Hum Genet. 2012;90(3):565-572.
- Tsurusaki Y, Okamoto N, Ohashi H, et al. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012;44(4):376-378.
- Kellermayer R, Kitagawa S, Redel CA, Cass DL, Belmont JW, Klish W. Upper gastrointestinal malformations in Coffin-Siris syndrome. Am J Med Genet A. 2007;143A(13):1519-1521.
- Fleck BJ, Pandya A, Vanner L, Kerkering K, Bodurtha J. Coffin-Siris syndrome: review and presentation of new cases from a questionnaire study. Am J Med Genet. 2001;99(1):1-7.