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) [1]. Although some mutations are inherited (according to an autosomal dominant pattern), many cases of CSS occur de novo [2].

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) [3]. 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 [4] [5]. 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 [5] [6].

• Gaucher Disease

  Cogan oculomotor apraxia can occur isolated, in the combination with neurological findings, and as part of a syndrome (e.g., Joubert syndrome, Gaucher disease type 3, ataxia-telangiectasia). [nature.com]

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 [7]. 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 [2].

You can help by adding to it. ( January 2018 ) Treatment [ edit ] There is no known cure or standard for treatment. Treatment is based on symptoms and may include physical, occupational and speech therapy and educational services as well. [en.wikipedia.org]

Such treatment may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child’s treatment. [rarediseases.org]

Management and treatment Treatment is essentially supportive and symptomatic. Occupational, physical and speech therapy are recommended. [orpha.net]

However, currently there is no experience with growth hormone treatment in CSS6; although children with CSS6 have short stature, GH treatment will not be administered temporarily. [frontiersin.org]

Prognosis The prognosis is poor in severely affected individuals, with aspiration pneumonia and seizures reported in childhood. The documents contained in this web site are presented for information purposes only. [orpha.net]

Studies Hand Deformities, Congenital/etiology* Hand Deformities, Congenital/genetics Hearing Loss, Sensorineural/etiology* Hearing Loss, Sensorineural/genetics Humans Intellectual Disability/etiology* Intellectual Disability/genetics Micrognathism/etiology [ncbi.nlm.nih.gov]

Etiology Heterozygous mutation or genomic rearrangement in the following five genes have been reported to be causative for CSS (highest to lowest proportion of reported cases): ARID1B (6q25.3), SMARCA4 (19p13.3), SMARCB1 (22q11.23), ARID1A (1p36.1-p35 [orpha.net]

On this page: Article: Epidemiology Clinical presentation Pathology References It occurs more frequently in females (with a M:F of ~4:1). [radiopaedia.org]

Summary Epidemiology More than 100 cases of confirmed CSS have been clinically reported to date. Exact prevalence and incidence are not known but the disorder is probably under-recognized. [orpha.net]

We conclude that haploinsufficiency of SMARCA4 is a valid pathophysiological mechanism for the establishment of a CSS-like phenotype. [karger.com]

Research in this section aims to get insight into the genetic, pathophysiologic and functional mechanisms of inherited and inborn errors of human development and differentiation. Research in this section involves two different topics: 1). [lumc.nl]

They hope that future studies will do more to uncover why only some people with mutations present the associated disease and make strides in preventative medicine. [popsci.com]

Prevention - Coffin-Siris syndrome Not supplied. Diagnosis - Coffin-Siris syndrome At present, the diagnosis of Coffin-Siris syndrome is based upon clinical findings. There are no laboratory tests that can confirm the disorder. [checkorphan.org]

[…] deficiencies has not prevented the mental retardation or neurologic abnormalities 45. [slideshare.net]

Neonatologists balanced out the amount of oxygen and pressure he was getting from the vent in order to prevent back up of blood in the lungs and allow the right amount of blood to go to his body. [gofundme.com]

During infancy, treatment may also require measures to help prevent or aggressively treat respiratory infections. Early intervention may be important in ensuring that affected children reach their potential. [rarediseases.org]

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.