FaCD Online Syndrome Fact Sheet

Last updated: 30 Jan 2013

Name: Uveal Melanoma, Familial

Synonym: Ocular Melanoma, Familial Clustering of

Mode of Inheritance: AD?

OMIM number: 155720  


BAP1, mapped to 3p21.1
CDKN2A/p16(INK4), mapped to 9p21

Tumor features

melanoma, uveal (choroidal, ciliary body, iris)/ocular

Tumor features (possible)

melanoma, cutaneous

Non-tumor features

dysplastic/atypical nevi


Uveal melanomas (UM) include melanomas of the choroid, ciliary body and choroid[1] and have been reported to cluster in families[2-5,16,16]. At least 0.6% of UM cases are familial[6]. A recent study reported close to 12% of UM patients with a family history suggestive of hereditary cancer[17]. It is assumed that an inherited predisposition to develop UM underlies part of the familial clusters[6]. Uveal and cutaneous melanomas and dysplastic/atypical nevi may occur in the same patient, in up to 2% of UM patients, or family[7,13,17]. A subset of these cases may represent Familial Atypical Multiple Mole Melanoma syndrome (FAMMM)[8]. The majority of familial UM cases is probably not a variant of FAMMM[3].
The genetics of familial UM are unclear[9]. In rare cases a p16 mutation is detected[12,14], but no mutations in CDK4, p14, p15 and BRCA2 genes have been detected in sporadic familial UM cases so far[10-12]. Some cases may be caused by germline BAP1 mutations.


[1] Grin JM, Grant-Kels JM, Grin CM, Berke A, Kels BD. Ocular melanomas and melanocytic lesions of the eye. J Am Acad Dermatol 38[5], 716-730. 1998.
[2] Canning CR, Hungerford J. Familial uveal melanoma. Br J Ophthalmol 1988; 72(4):241-243.
[3] Singh AD, Wang MX, Donoso LA, Shields CL, De Potter P, Shields JA. Genetic aspects of uveal melanoma: A brief review. Semin Oncol 23[6], 768-772. 1996.
[4] Young LH, Egan KM, Walsh SM, Gragoudas ES. Familial uveal melanoma. Am J Ophthalmol 1994; 117(4):516-520.
[5] Bercher L, Munier F, Zografos L, Schorderet D, Egger E, Chamot L. [Familial uveal melanoma]. Klin Monatsbl Augenheilkd 1995; 206(5):384-387.
[6] Singh AD, Wang MX, Donoso LA, Shields CL, De Potter P, Shields JA, Elston RC, Fijal B. Familial uveal melanoma .3. Is the occurrence of familial uveal melanoma coincidental? Arch Ophthalmol 114[9], 1101-1104. 1996.
[7] Van Hees CLM, Jager MJ, Bleeker JC, Kemme H, Bergman W. Occurrence of cutaneous and uveal melanoma in patients with uveal melanoma and their first degree relatives. Melanoma Res 8[2], 175-180. 1998.
[8] Oosterhuis JA, Went LN, Lynch HT. Primary choroidal and cutaneous melanomas, bilateral choroidal melanomas, and familial occurrence of melanomas. Br J Ophthalmol 1982; 66(4):230-233.
[9] Houlston RS, Damato BE. Genetic predisposition to ocular melanoma. Eye 13, 43-46. 1999.
[10] Singh AD, Croce CM, Wary KK, Shields JA, Donoso LA, Shields CL, Huebner K, Ohta M. Familial uveal melanoma: absence of germline mutations involving the cyclin-dependent kinase-4 inhibitor gene (p16). Ophthalmic Genet 1996; 17(1):39-40.
[11] Soufir N, Bressac-de Paillerets B, Desjardins L, Levy C, Bombled J, Gorin I, Schlienger P, Stoppa-Lyonnet D. Individuals with presumably hereditary uveal melanoma do not harbour germline mutations in the coding regions of either the P16INK4A, P14ARF or cdk4 genes. Br J Cancer 2000; 82(4):818-822.
[12] Hearle N, Damato BE, Humphreys J, Wixey J, Green H, Stone J, Easton DF, Houlston RS. Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma. Investigative ophthalmology & visual science 2003; 44(2):458-62.
[13] Smith JH, Padnick-Silver L, Newlin A, Rhodes K, Rubinstein WS. Genetic study of familial uveal melanoma: association of uveal and cutaneous melanoma with cutaneous and ocular nevi. Ophthalmology 2007; 114(4):774-9.
[14] Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, Azizi E, Bianchi-Scarra G, Bishop DT, Bressac-de Paillerets B, Bruno W, Calista D, Cannon Albright LA, Demenais F, Elder DE, Ghiorzo P, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, Mackie RM, Magnusson V, Mann GJ, Niendorf K, Newton Bishop J, Palmer JM, Puig S, Puig-Butille JA, de Snoo FA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E, . High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer research 2006; 66(20):9818-28.
[15] Krygier G, Lombardo K, Vargas C, Alvez I, Costa R, Ros M, Echenique M, Navarro V, Delgado L, Viola A, Musé A. Familial uveal melanoma: report on three sibling cases. The British journal of ophthalmology 2001; 85(8):1007-8.
[16] Kodjikian L, Nguyen K, Lumbroso L, Gauthier-Villars M, Chauvel P, Plauchu H, Sterkers M, Devouassoux M, Grange JD. Familial uveal melanoma: a report on two families and a review of the literature. Acta ophthalmologica Scandinavica 2003; 81(4):389-95.
[17] Abdel-Rahman MH, Pilarski R, Ezzat S, Sexton J, Davidorf FH. Cancer family history characterization in an unselected cohort of 121 patients with uveal melanoma. Fam Cancer. 2010 Feb 16. [Epub ahead of print]