Contribution of Mendelian disorders to common chronic disease: opportunities for recognition, intervention, and prevention

Am J Med Genet C Semin Med Genet. 2004 Feb 15;125C(1):50-65. doi: 10.1002/ajmg.c.30008.


Recognizing Mendelian disorders should improve health care for persons with strong familial risks for common chronic diseases. The Online Mendelian Inheritance in Man (OMIM) database was reviewed to identify Mendelian disorders featuring 17 common chronic diseases, including 9 cardiovascular conditions, diabetes, and 7 common cancers. Mendelian disorders were selected if any one of the 17 diseases was reported in more than two families manifesting in adulthood. Patterns of chronic diseases and modes of inheritance associated with these Mendelian disorders are described. The GeneTests/Reviews database and other websites were reviewed to determine availability of genetic testing and management and prevention recommendations for the selected disorders. Of 2,592 (OMIM) entries reviewed, 188 Mendelian disorders were selected. Most (67.7%) are autosomal dominant disorders. Almost half (45.8%) feature combinations of the chronic diseases under study. At least one gene is known for 68.8% of the selected disorders, and clinical genetic testing is available for 55% of disorders. Guidelines for management and prevention are available for 33.9% of these, ranging from recommendations for supportive care to guidelines for managing affected persons and screening relatives. Significant clinical heterogeneity exists for Mendelian disorders that might present as strong family histories of common chronic diseases. Recognition of the different combinations of diseases within a pedigree, including mode of inheritance and heritable disease risk factors, facilitates diagnosis of these Mendelian disorders. Genetic testing is available for most disorders, which can further clarify the genetic risk, and for some, recommendations for management and prevention are available. However, evidence-based guidelines are needed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Chronic Disease* / therapy
  • Databases, Genetic*
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / prevention & control
  • Genetic Diseases, Inborn / therapy
  • Genetic Predisposition to Disease*
  • Genetic Testing*
  • Humans
  • Inheritance Patterns*
  • Internet
  • Medical History Taking
  • Pedigree
  • Practice Guidelines as Topic*