Hereditary SWI/SNF complex deficiency syndromes

Semin Diagn Pathol. 2018 May;35(3):193-198. doi: 10.1053/j.semdp.2018.01.002. Epub 2018 Feb 1.


The SWItch Sucrose non-fermentable (SWI/SNF) complex is a highly conserved multi-subunit complex of proteins encoded by numerous genes mapped to different chromosomal regions. The complex regulates the process of chromatin remodelling and hence plays a central role in the epigenetic regulation of gene expression, cell proliferation and differentiation. During the last three decades, the SWI/SNF complex has been increasingly recognized as a central molecular event driving the initiation and/or progression of several benign and malignant neoplasms of different anatomic origin and having diverse histomorphological appearance. Atypical teratoid/rhabdoid tumors (AT/RT) and renal/extrarenal malignant rhabdoid tumors of childhood, epithelioid sarcoma and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) represent the most commonly recognized SWI/SNF-driven neoplasms. Approximately one-third of pediatric malignant rhabdoid tumors are linked to germline SWI/SNF alterations (SMARCB1/INI1, rarely SMARCA4) resulting in occasional familial clustering of these highly aggressive malignancies (so-called rhabdoid tumor predisposition syndrome, RTPS, types 1 and 2, respectively). However, more recently, inherited SWI/SNF-deficiency has been linked to several benign syndromic tumors including a subset of familial schwannomatosis (linked to SMARCB1) and multiple meningiomas (linked to SMARCE1) as well as others. Beyond neoplasms, several congenital developmental functional disorders such as Coffin-Siris syndrome and intellectual disability are now known to be SWI/SNF-related. The latter are essentially not associated with SWI/SNF-driven neoplasms, although at least anecdotal cases have documented concurrence of both neoplastic and developmental disorders. This review summarizes the most important SWI/SNF-driven diseases with a main focus on neoplasms.

Keywords: Malignant rhabdoid tumor; Rhabdoid tumor predisposition syndrome; SMARCA4; SMARCB1; SWI/SNF complex; Small cell carcinoma of ovary, hypercalcemic type.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA Helicases / genetics
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Heredity
  • Humans
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / pathology
  • Neoplastic Syndromes, Hereditary / therapy
  • Nuclear Proteins / genetics
  • Pedigree
  • Phenotype
  • Predictive Value of Tests
  • SMARCB1 Protein / genetics
  • Transcription Factors / genetics*


  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases