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Coffin-Siris Syndrome.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2013 Apr 4 [updated 2016 May 12].

Author information

Division of Medical Genetics and Metabolism, Children’s Hospital of the King’s Daughters, Norfolk, Virginia
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Institut für Humangenetik, Heinricht-Heine-Universität Düsseldorf, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
Institute of Human Genetics and Center for Molecular Medicine Cologne, University Medical Faculty, University of Cologne, Cologne, Germany
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania



Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment.


Before the molecular basis was known, the diagnosis of CSS was based on clinical findings. With the recent detection of heterozygous pathogenic variants in ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1, or SOX11 in some (but not all) individuals with CSS, the diagnostic features have become more clearly described for classic cases. A few individuals diagnosed with CSS on a clinical basis have been found to have pathogenic variants in SMARCA2 or PHF6; on reevaluation, the phenotype of these individuals was most consistent with Nicolaides-Baraitser syndrome or Borjeson-Forssman-Lehmann syndrome, respectively.


Treatment of manifestations: Occupational, physical, and/or speech therapies to optimize developmental outcomes. Feeding therapy, nutritional supplementation and/or gastrostomy tube placement as needed to meet nutritional needs. Routine management of ophthalmologic abnormalities and hearing loss. Surveillance: Yearly evaluation by a developmental pediatrician to assess developmental progress and therapeutic and educational interventions; follow up with a gastroenterologist and feeding specialists as needed to monitor feeding and weight gain. Routine follow up of ophthalmologic and/or audiologic abnormalities.


CSS caused by a heterozygous pathogenic variant in one of six genes (ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1, and SOX11) is inherited in an autosomal dominant manner, but most commonly results from a de novo pathogenic variant. If the pathogenic variant has been identified in a family member, prenatal testing for pregnancies at increased risk is possible.

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