Occasionally GIST may run in families due to an inherited germline mutation. There are fewer than 20 reports of familial GIST in the medical literature.  In familial GIST the initial mutation is already present in all the body's cells, meaning that the first step toward developing GIST has occurred before birth. Therefore, there is a high probability that multiple GISTs will develop, and at a younger adult age than in sporadic GIST.

Figure 10. Autosomal dominant inheritance pattern. Image used with permission of Clinical Tools, Inc. via www1.geneticsolutions.com

The pattern of inheritance in many of these families has been an autosomal dominant pattern, implying that each child of an affected parent has a 50% chance of inheriting the mutant gene.  The figure above illustrates that the affected father passes on the trait to half of his offspring.  The affected offspring then have a 50% chance of passing it on to each of their children.  Unaffected offspring cannot pass on the trait, as ilustrated in the following figure.  Note, however, that in the case of familial GIST, people who inherit the mutant gene do not necessarily develop GIST, or may not do so until middle age or later.

Figure 11. Autosomal dominant pedigree across generations. Image used with permission of Clinical Tools, Inc. via www1.geneticsolutions.com

Individuals with familial GIST often show excess growth called hyperplasia of interstitial cells of Cajal in the intestinal nerve centers called the myenteric plexus. This hyperplasia is apparently a precursor condition to the development of multiple tumors. Individuals in some families may show areas of hyperpigmentation (darker skin) on the face, neck, hands, feet, or other areas. 

Mutations of the gene encoding the KIT receptor have been identified in several affected families (Nishida et al, 1998; Beghini et al, 2001; O'Brien et al, 1999; Hirota et al, 2000; Isozaki et al, 2000; Handra-Luca et al, 2001; Maeyama et al, 2001; Hirota et al, 2002; Chen et al, 2002; Robson et al, 2004; Hartmann et al, 2005; Kim et al, 2005; O'Riain et al, 2005; Carballo et al, 2005; Li et al, 2005; Lasota and Miettinen, 2006; Kang et al, 2006).  It is important to note that different families display different KIT gene mutations.  The family described by Hartmann et al (2005) displayed a unique mutation in exon 8 of the gene for KIT, an exon whose mutation has not previously been associated with GISTs.

Mutation in the gene encoding PDGFRA has been reported in one family (Chompret et al, 2004).  There is one report of GISTs occurring in a father and son who did not have a germline mutation of the KIT gene but did have apparently sporadic KIT mutations (Yeh et al, 2006).

(To access a PubMed list of all the papers cited above, see the bibliography entry for Familial GIST on our "Search by Topic" GIST Bibliography page).

Please also see the section in our Ask the Professional series on "Case History of A Family with GIST" by Jonathan C. Trent, MD PhD.  This poster includes illustrations of hyperplasia of interstitial cells of Cajal, as well as describing the affected proportion of one family.