Familial uveal melanoma: report on three sibling cases

Familial uveal melanoma: a report on two families and a review of the literature

“…Based on the limited number of cases studied, an autosomal dominant mode of inheritance with incomplete penetrance has been postulated to explain the familial involvement (Lynch et al 1968), as some individuals were affected over many generations (vertical transmission) (Thompson et al 1991;Singh et al 1996a). This view is supported by the findings that some of the predisposing factors for uveal melanoma, such as neurofibromatosis type 1 and possibly FAM-M syndrome, are also inherited as autosomal dominant traits (Gonder et al 1981;Oosterhuis et al 1982;Specht & Smith 1988;Singh & Donoso 1993;Krygier et al 2001). However, a review of published reports on sets of kindred with familial uveal melanoma revealed that involvement over many generations was very rare and usually only one additional first-degree relative in a given family had uveal melanoma (Pfingst & Graves 1921;Waardenburg 1940;Paton & Thomas 1959;Bowen et al 1964;Lynch et al 1968;Tasman 1970;Simons et al 1983;Gutmann 1985;Canning & Hungerford 1988;Young et al 1994;Bercher et al 1995;Singh et al 1996a;Van Hees et al 1998;Singh et al 2000;Soufir et al 2000).…”

“…A second primary malignant neoplasm in the probands (Green et al 1978; Young et al 1994; Singh et al 1996a; Krygier et al 2001) or malignant neoplasm in the probands' relatives (Lynch et al 1968; Green et al 1978; Young et al 1994; Singh et al 1996a; Krygier et al 2001) seems to be rather common. Singh et al (1996a) estimated that the presence of a second primary malignant neoplasm was four times higher in probands of familial uveal melanoma than the expected prevalence of other cancers (all sites), based on data on age‐ and sex‐specific prevalence derived from the Connecticut Tumor Registry.…”

“…To our knowledge, only 69 families (150 patients) have been reported so far as exhibiting uveal melanomas in more than one family member. Sixty‐one families had one affected member in addition to the proband (Pfingst & Graves 1921; Waardenburg 1940; Paton & Thomas 1959; Bowen et al 1964; Lynch et al 1968; Tasman 1970; Simons et al 1983; Gutmann 1985; Canning & Hungerford 1988; Young et al 1994; Bercher et al 1995; Singh et al 1996a; Van Hees et al 1998; Singh et al 2000; Soufir et al 2000); six families had two additional affected members (Lynch et al 1968; Green et al 1978; Walker et al 1979; Bercher et al 1995; Singh et al 1996a; Krygier et al 2001); one family had three (Young et al 1994) and one family had four additional affected members (Silcock 1892; Davenport 1927). Our study of two additional cases of family uveal melanoma increases the total number of familial clusters reported in the literature.…”

“…Familial predisposition to uveal melanoma might be a component of a generalized inherited predisposition to cancer. This is suspected but remains to be established (Krygier et al 2001). It would also be expected to have an effect on familial uveal melanoma kindred who have not yet manifested an uveal melanoma.…”

“…In some cases, it may be inherited, although the occurrence of familial uveal melanoma is rare, comprising only 0.6% of all uveal melanoma patients (Singh et al 1996a). Since the initial report of a case of hereditary uveal melanoma by Silcock (1892), 69 additional families (150 patients) have been described (Pfingst & Graves 1921; Davenport 1927; Waardenburg 1940; Paton & Thomas 1959; Bowen et al 1964; Lynch et al 1968; Tasman 1970; Green et al 1978; Walker et al 1979; Simons et al 1983; Gutmann 1985; Canning & Hungerford 1988; Young et al 1994; Bercher et al 1995; Van Hees et al 1998; Singh et al 2000; Soufir et al 2000; Krygier et al 2001). This report describes the case histories of two additional families, each of which included two members with uveal melanomas (two cousins and a pair of siblings).…”