Familial Multiple Lipomatosis
Familial multiple lipomatosis (FML) is a rare disorder of lipomas on the neck, arms, abdomen and thighs(1, 2). It was first described in 1857 by Murchison and later reported(3). It is most likely an autosomal dominant disorder(4) and is seen in men and women(5). The genetic defect is thought to be secondary to a translocation involving high-mobility-group protein isoform I-C (HMGIC)on chromosome 12 and the lipoma preferred partner gene (LLP) on chromosome 3(6, 7), however, chromosomal abnormalities are not seen in all families(8), and the lipomas evaluated for translocation were a small number of a much larger group of mesenchymal tumors(9). No evaluation of DNA from families with FML has been undertaken to date. The lipomas vary in size, are rubbery, can be pulled in entirety with force through a small incision and make an audible noise when cutting suggestive of increased connective tissue. In general, the lipomas are not painful unless irritated or traumatized regularly(1, 2, 10), although it has been reported that the lipomas were painful when growing but not after their size had stabilized(11-13). Recent data suggests that individuals with FML may go on to develop pain and other symptoms associated with AD(14). We know of four families with FML in which at least one individual in the family with lipomas developed signs and symptoms of AD suggesting that this is not an uncommon phenomenon in this rare disease. In addition, other investigators have described AD in a family with FML(14, 15). Pack described this phenomenon as FML with lipoma dolorosa, stating that it was entirely different from AD(16). These data suggest that without performing a biopsy to evaluate whether the fat is rubbery and cohesive (FML) versus soft and easily broken (AD), that it will be difficult to distinguish AD from FML with lipoma dolorosa. In addition, it suggests that the criteria for determining when to label signs and symptoms as AD versus lipoma dolorosa be further examined.
Learn more here: www.fatdisorders.org This website is an excellent resource for FML.
References
1. Rabbiosi, G., Borroni, G., and Scuderi, N. (1977) Familial multiple lipomatosis. Acta Derm Venereol. 57, 265-267.
2. Mohar, N. (1980) Familial multiple lipomatosis. Acta Derm Venereol. 60, 509-513.
3. Murchison, C. Cases of hereditary, muItipIe,fatty tumors. . Edinburgb M. J. 2, 1091
4. Korn-Heydt, G. E. (1969) Aplasien, hyperplasien, Tumoren. 4. Lipome. In Handbuch der Haut-und Geschlechtsktrankheiten Erganzungswerk (Jadassohn, J., ed) Vol. VII pp. 582-585, Springer, Berlin
5. Ersek, R. A., Lele, E., Surak, G. S., Denton, D. R., and McCue, K. (1989) Hereditary progressive nodular lipomatosis: a report and selective review of a new syndrome. Ann Plast Surg. 23, 450-455.
6. Schoenmakers, E. F., Wanschura, S., Mols, R., Bullerdiek, J., Van den Berghe, H., and Van de Ven, W. J. (1995) Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet. 10, 436-444.
7. Mrozek, K., Karakousis, C. P., and Bloomfield, C. D. (1993) Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3. Cancer Res. 53, 1670-1675.
8. Gologorsky, Y., Gologorsky, D., Yarygina, A. S., Surti, U., and Zirwas, M. J. (2007) Familial multiple lipomatosis: report of a new family. Cutis. 79, 227-232.
9. Mrozek, K., and Bloomfield, C. D. (1996) Have cancer cytogeneticists been wrong in assigning chromosome 12 breakpoints in benign tumors? Genes Chromosomes Cancer. 15, 195-196.
10. Toy, B. R. (2003) Familial multiple lipomatosis. Dermatol Online J. 9, 9.
11. Kurzweg, F. T., and Spencer, R. (1951) Familial multiple lipomatosis. Am J Surg. 82, 762-765.
12. Hellier, F. F. (1935) Hereditary muItipIe Iipomata. Lancet 1, 204
13. Bonnefous, R., and Valdiguie, A. (1924) Hypercholesterinemia et Lipomatose. Ann. de dermat. et sypb. 5, 290
14. Campen, R., Mankin, H., Louis, D. N., Hirano, M., and Maccollin, M. (2001) Familial occurrence of adiposis dolorosa. J Am Acad Dermatol 44, 132-136
15. Campen, R. B., Sang, C. N., and Duncan, L. M. (2006) Case records of the Massachusetts General Hospital. Case 25-2006. A 41-year-old woman with painful subcutaneous nodules. N Engl J Med. 355, 714-722.
16. Pack, G. T., and Ariel, I. M. (1958) Tumors of the Soft Somatic Tissues: A Clinical Treatise, Hoeber-Harper, New York
Learn more here: www.fatdisorders.org This website is an excellent resource for FML.
References
1. Rabbiosi, G., Borroni, G., and Scuderi, N. (1977) Familial multiple lipomatosis. Acta Derm Venereol. 57, 265-267.
2. Mohar, N. (1980) Familial multiple lipomatosis. Acta Derm Venereol. 60, 509-513.
3. Murchison, C. Cases of hereditary, muItipIe,fatty tumors. . Edinburgb M. J. 2, 1091
4. Korn-Heydt, G. E. (1969) Aplasien, hyperplasien, Tumoren. 4. Lipome. In Handbuch der Haut-und Geschlechtsktrankheiten Erganzungswerk (Jadassohn, J., ed) Vol. VII pp. 582-585, Springer, Berlin
5. Ersek, R. A., Lele, E., Surak, G. S., Denton, D. R., and McCue, K. (1989) Hereditary progressive nodular lipomatosis: a report and selective review of a new syndrome. Ann Plast Surg. 23, 450-455.
6. Schoenmakers, E. F., Wanschura, S., Mols, R., Bullerdiek, J., Van den Berghe, H., and Van de Ven, W. J. (1995) Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet. 10, 436-444.
7. Mrozek, K., Karakousis, C. P., and Bloomfield, C. D. (1993) Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3. Cancer Res. 53, 1670-1675.
8. Gologorsky, Y., Gologorsky, D., Yarygina, A. S., Surti, U., and Zirwas, M. J. (2007) Familial multiple lipomatosis: report of a new family. Cutis. 79, 227-232.
9. Mrozek, K., and Bloomfield, C. D. (1996) Have cancer cytogeneticists been wrong in assigning chromosome 12 breakpoints in benign tumors? Genes Chromosomes Cancer. 15, 195-196.
10. Toy, B. R. (2003) Familial multiple lipomatosis. Dermatol Online J. 9, 9.
11. Kurzweg, F. T., and Spencer, R. (1951) Familial multiple lipomatosis. Am J Surg. 82, 762-765.
12. Hellier, F. F. (1935) Hereditary muItipIe Iipomata. Lancet 1, 204
13. Bonnefous, R., and Valdiguie, A. (1924) Hypercholesterinemia et Lipomatose. Ann. de dermat. et sypb. 5, 290
14. Campen, R., Mankin, H., Louis, D. N., Hirano, M., and Maccollin, M. (2001) Familial occurrence of adiposis dolorosa. J Am Acad Dermatol 44, 132-136
15. Campen, R. B., Sang, C. N., and Duncan, L. M. (2006) Case records of the Massachusetts General Hospital. Case 25-2006. A 41-year-old woman with painful subcutaneous nodules. N Engl J Med. 355, 714-722.
16. Pack, G. T., and Ariel, I. M. (1958) Tumors of the Soft Somatic Tissues: A Clinical Treatise, Hoeber-Harper, New York
