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Coffin-Siris Syndrome


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) [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].

Coarctation of the Aorta
  • He showed the CSS phenotype and coarctation of the aorta. Sox11 is known to be associated with cardiac outflow development in mouse studies. Therefore, cardiac anomalies might be an important complication in patients with SOX11 mutations.[ncbi.nlm.nih.gov]
  • Clinically, the patient presented with extreme obesity, macrocephaly, hepatomegaly, hyperinsulinism and polycystic ovarian syndrome (PCOS), which have previously not been described in CSS patients.[ncbi.nlm.nih.gov]
  • Vals MA, Oiglane-Shlik E, Nõukas M, Shor R, Peet A, Kals M, Ann Kivistik P, Metspalu A, Ounap K (2014) Coffin-Siris Syndrome with obesity, macrocephaly, hepatomegaly and hyperinsulinism caused by a mutation in the ARID1B gene.[en.wikipedia.org]
  • However, unlike other patients described, she has extreme macrocephaly, obesity with hepatomegaly, PCOS, hyperinsulinism and metabolic syndrome.[nature.com]
  • […] characteristic facial gestalt with bitemporal narrowing, prominent supraorbital ridges, synophrys, a short nose and dental anomalies, tapering fingers with brachytelephalangy, clinodactyly and hypoplastic nails, short toes with hypoplastic nails, and linear skin hyperpigmentation[ncbi.nlm.nih.gov]
Round Face
  • The craniofacial manifestations include large boxy head, round face, hypertelorism with downslanting palpebral fissures and wide mouth. Other manifestations include brachydactyly, fifth finger clinodactyly and ventricular septal defect.[ncbi.nlm.nih.gov]
  • Phenotypically, she demonstrated acanthosis nigricans on her neck, armpits and inguinal areas, a wide round face, long sparse and loose hair, hypertrichosis, dysmorphic ears, brachydactyly, short F5 ( Figure 1d ), syndactyly of T2-3 and dysmorphic nails[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].


  • (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]
  • Coffin Siris Syndrome Treatment The treatment of the Coffin Siris Syndrome in children may vary depending on the different symptoms present in the patient. However, no treatment can completely cure the Coffin Siris Syndrome.[medicalsubstance.com]
  • Management and treatment Treatment is essentially supportive and symptomatic. Occupational, physical and speech therapy are recommended.[orpha.net]
  • Treatment - Coffin-Siris syndrome The treatment or therapy required for children with Coffin-Siris syndrome is based on the particular symptoms of each individual.[checkorphan.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]
  • Prognosis - Coffin-Siris syndrome Infants born with Coffin-Siris syndrome may experience a delay or absence of motor and mental activities, but with support can live into adulthood.[checkorphan.org]
  • Recently, SMARCA4 mutations have been also associated with a rare and extremily aggressive form of ovarian cancer, small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), characterized by dismal prognosis and poor response to chemotherapy.[iris.unipv.it]
  • The prognosis when Syd was born was not very good. We were told she would likely only be with us for a year. After three months in the neonatal intensive-care unit, we brought her home to love her for as long as we could.[theglobeandmail.com]


  • The etiology of this syndrome is unknown. We report on an 11-year-old girl with Coffin-Siris syndrome and a de novo, apparently balanced reciprocal translocation between chromosomes 7 and 22 [t(7;22)(q32;q11.2)].[ncbi.nlm.nih.gov]
  • The etiology of this syndrome remains uncertain.[ncbi.nlm.nih.gov]
  • The recent identification of molecular etiologies has served to effectively characterize a large set of patients who have been described with Coffin-Siris between the time of its initial description and the present.[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]
  • The etiology of MRKH syndrome is unknown, but it is believed to be due to interrupted embryological development in weeks 8 to 12 of gestation.[jmedicalcasereports.biomedcentral.com]


  • The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations.[books.google.com]
  • 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]
  • Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update . 2011 Nov 6. [Medline] . Liu K, Motan T, Claman P.[emedicine.medscape.com]
  • The epidemiology of mental retardation: challenges and opportunities in the new millennium . Ment. Retard. Dev. Disabil. Res. Rev. 8 , 117–134 (2002). 22. Lubs, H. A. , Stevenson, R. E. & Schwartz, C. E.[nature.com]
Sex distribution
Age distribution


  • 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]


  • 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]
  • 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]
  • […] 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]
  • If the appliance fails to prevent obliquity of the occlusal plane, then elongation of the ramus or mandibular distraction is indicated at age 6-12 years during mixed dentition.[emedicine.medscape.com]



  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.

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Last updated: 2018-09-01 18:55