Format

Send to

Choose Destination
See comment in PubMed Commons below

Coffin-Siris Syndrome.

Source

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

Author information

1
Division of Medical Genetics and Metabolism, Children’s Hospital of the King’s Daughters, Norfolk, Virginia
2
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
3
Institut für Humangenetik, Heinricht-Heine-Universität Düsseldorf, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
4
Institute of Human Genetics and Center for Molecular Medicine Cologne, University Medical Faculty, University of Cologne, Cologne, Germany
5
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
6
Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Excerpt

CLINICAL CHARACTERISTICS:

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.

DIAGNOSIS/TESTING:

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.

MANAGEMENT:

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.

GENETIC COUNSELING:

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.

Copyright © 1993-2018, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Support Center