MIM Entry: 151900
%151900 LIPOMATOSIS, MULTIPLE
;;LIPOMATOSIS, FAMILIAL MULTIPLE; FML;;
Familial multiple lipomatosis is a rare autosomal dominant disorder
characterized by numerous encapsulated lipomas on the trunk and
extremities (Keskin et al., 2002).
Stephens and Isaacson (1959) observed 17 cases in 3 generations. Usually
the condition did not become evident until the age of about 35 years,
although in 1 case lipomas were present at age 9. The gastrointestinal
tract may be involved (Lang et al., 1959).
Golsch and Worret (1995) described a family with 9 cases of familial
multiple lipomatosis in 3 generations. The oldest living member of the
family suffered from a nonalcoholic peripheral neuropathy.
Polyneuropathy has been described in association with multiple symmetric
lipomatosis (151800) and may be an intrinsic part of that disorder. Its
relationship to familial multiple lipomatosis is less clear.
Keskin et al. (2002) reported a large family in which 8 members of 3
generations had multiple lipomatosis. In 1 patient, the lipomas occurred
only on the neck, but in others they occurred on the trunk, the upper
extremities, and the thighs. The lipomas arose in the third or fourth
decade in all but 1, who had onset at age 14 years.
Keskin et al. (2002) reported multiple lipomas in 8 members of 3
generations of a family with male-to-male transmission.
Dal Cin et al. (1988) reported on the cytogenetic analysis of 3
different lipomas from a patient with multiple subcutaneous lipomas. Two
distinct reciprocal translocations were observed, both with breakpoints
at 12q14. The reciprocal translocation t(3;12)(q28;q14) was found in 2
lipomas from this patient; t(1;12)(q34.2;q14) was seen in the third. The
authors noted that 2 previously described translocations involving
chromosome 12q14 also had breakpoints in the region of 3q27-q28.
Heim et al. (1988) concluded, on the basis of cytogenetic analysis of
tumor cells from 50 lipomas, that 4 main cytogenetic subtypes can be
recognized: (1) tumors with normal karyotype (18 cases); (2) tumors with
rearrangements of 12q13-q14 (18 cases); (3) tumors with ring chromosomes
(6 cases); and (4) tumors with other clonal changes (8 cases). All 6
tumors with ring marker chromosomes were histopathologically classified
as atypical lipomas. All 7 multiple lipomas were karyotypically normal.
Sreekantaiah et al. (1991) found abnormalities of chromosome 12 in 34 of
92 patients with lipomas.
The distinctness of benign lipomas, including multiple lipomatosis, from
myxoid liposarcoma (613488) was indicated by the findings of Mrozek et
al. (1993) that the chromosome 12 breakpoint in myxoid liposarcoma is at
12q13.3, as reported by many others, but that the breakpoint in benign
lipoma, including multiple lipomatosis, is more distally situated, at
12q15. They suggested that the more distal location is identical to that
found in other benign tumors such as uterine leiomyoma (150699) and
pleomorphic adenoma of the salivary gland (181030).
In a note added in proof to their report of the HMGIC gene (600698) on
chromosome 12 involved in soft tissue tumors with translocations of
12q15, Schoenmakers et al. (1995) referred to the isolation and
sequencing of the lipoma-preferred-partner gene (LPP; 600700).
Chromosome 3 is the preferred partner in lipomas resulting from
translocation involving 12q15. Other translocation partners of 12q15
include chromosomes 1, 2, 4, 5, 6, 7, 10, 11, 13, 15, 17, 21, and X
(Sreekantaiah et al., 1991).
Ligon et al. (2005) reported an 8-year-old boy who had a de novo
pericentric inversion of chromosome 12, with breakpoints at p11.22 and
q14.3, and a phenotype that included extreme somatic overgrowth,
advanced endochondral bone and dental ages, a cerebellar tumor, and
multiple lipomas. At 27 months of age the patient showed macrocephaly,
bilateral bowing and multiple lipomas of the lower extremities, and
megaepiphyseal flaring of the femur and tibia at the knee joint. At the
age of 4 years, the patient showed disorganized and advanced dental age
of both erupted and unerupted teeth. Bone age was estimated at 13.5
years on a wrist radiograph taken at 8 years of age. The chromosomal
inversion was found to truncate HMGA2 (600698), a gene that encodes an
architectural factor involved in the etiology of many benign mesenchymal
tumors and that maps to the 12q14.3 breakpoint. Similar truncations of
mouse Hmga2 in transgenic mice result in somatic overgrowth and, in
particular, increased abundance of fat and lipomas (Arlotta et al.,
2000), features strikingly similar to those observed in the child.
Prontera et al. (2009) described a 5-year-old girl with
encephalocutaneous lipomatosis (ECCL; 613001) and a family history of
multiple lipomatosis. The patient had lipomas on the face, alopecia
areata, coloboma of iris, chorioretinitis, bilateral epibulbar dermoid,
complex partial crises, moderate tricuspid valve insufficiency,
increased pulmonary pressure, intracranial lipomas, leptomeningeal
angiomatosis, intracranial calcification, hypoplastic corpus callosum,
arachnoid cyst of the right temporal lobe, enlargement of the right
ventricle, microgyria of the temporal and occipital right lobes,
osteolytic lesion in the right jaw, including irregular zones of
calcification, ossification and dental elements (odontogenic jaw tumor),
moderate speech delay, and macrocephaly. Her father and her paternal
grandmother had multiple benign lipomas affecting limbs and trunk that
appeared during the second and third decade of life. Prontera et al.
(2009) suggested that HMGA2 may be a good candidate for both FML and
ECCL. They proposed that a germline mutation in the HMGA2 gene may be
responsible for dominant FML and that a somatic mutation in this gene
may be responsible for ECCL.
Heim et al. (1986); Humphrey and Kingsley (1938); Krabble and Bartels
(1944); Kurzweg and Spencer (1951); Limon et al. (1986); Rabbiosi
et al. (1977); Shanks et al. (1957); Turc-Carel et al. (1988); Turc-Carel
et al. (1986); Weinberg et al. (1980)
1. Arlotta, P.; Tai, A. K.-F.; Manfioletti, G.; Clifford, C.; Jay,
G.; Ono, S. J.: Transgenic mice expressing a truncated form of the
high mobility group I-C protein develop adiposity and an abnormally
high prevalence of lipomas. J. Biol. Chem. 275: 14394-14400, 2000.
2. Dal Cin, P.; Turc-Carel, C.; Sandberg, A. A.: Consistent involvement
of band 12q14 in two different translocations in three lipomas from
the same patient. Cancer Genet. Cytogenet. 31: 237-240, 1988.
3. Golsch, S.; Worret, W.-I.: Familial multiple lipomatosis with
polyneuropathy. Europ. J. Derm. 5: 283-285, 1995.
4. Heim, S.; Mandahl, N.; Kristoffersson, U.; Mitelman, F.; Roser,
B.; Rydholm, A.; Willen, H.: Reciprocal translocation t(3;12)(q27;q13)
in lipoma. Cancer Genet. Cytogenet. 23: 301-304, 1986.
5. Heim, S.; Mandahl, N.; Rydholm, A.; Willen, H.; Mitelman, F.:
Different karyotypic features characterize different clinicopathologic
subgroups of benign lipogenic tumors. Int. J. Cancer 42: 863-867,
6. Humphrey, A. A.; Kingsley, P. C.: Familial multiple lipomas: report
of a family. Arch. Derm. Syph. 37: 30-34, 1938.
7. Keskin, D.; Ezirmik, N.; Celik, H.: Familial multiple lipomatosis. Isr.
Med. Assoc. J. 4: 1121-1123, 2002.
8. Krabble, K. H.; Bartels, E. D.: La lipomatose circonscripte multiple.
Copenhagen: Munksgaard (pub.) 1944.
9. Kurzweg, F. T.; Spencer, R.: Familial multiple lipomatosis. Am.
J. Surg. 82: 762-765, 1951.
10. Lang, C. S.; Leagus, C.; Stahlgren, L. H.: Intestinal lipomatosis. Surgery 4 6:
11. Ligon, A. H.; Moore, S. D. P.; Parisi, M. A.; Mealiffe, M. E.;
Harris, D. J.; Ferguson, H. L.; Quade, B. J.; Morton, C. C.: Constitutional
rearrangement of the architectural factor HMGA2: a novel human phenotype
including overgrowth and lipomas. Am. J. Hum. Genet. 76: 340-348,
12. Limon, J.; Turc-Carel, C.; Dal Cin, P.; Rao, U.; Sandberg, A.
A.: Recurrent chromosome translocations in liposarcoma. (Letter) Cancer
Genet. Cytogenet. 22: 93-94, 1986.
13. Mrozek, K.; Karakousis, C. P.; Bloomfield, C. D.: 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, 1993.
14. Prontera, P.; Stangoni, G.; Manes, I.; Mencarelli, A.; Donti,
E.: Encephalocraniocutaneous lipomatosis (ECCL) in a patient with
history of familial multiple lipomatosis (FML). (Letter) Am. J. Med.
Genet. 149A: 543-545, 2009.
15. Rabbiosi, G.; Borroni, G.; Scuderi, N.: Familial multiple lipomatosis. Acta
Derm. Venerol. 57: 265-267, 1977.
16. Schoenmakers, E. P. P. M.; Wanschura, S.; Mols, R.; Bullerdiek,
J.; Van den Berghe, H.; Van de Ven, W. J. M.: Recurrent rearrangements
in the high mobility group protein gene, HMGI-C, in benign mesenchymal
tumours. Nature Genet. 10: 436-444, 1995.
17. Shanks, J. A.; Paranchych, W.; Tuba, J.: Familial multiple lipomatosis. Cana d.
Med. Assoc. J. 77: 881-884, 1957.
18. Sreekantaiah, C.; Leong, S. P. L.; Karakousis, C. P.; McGee, D.
L.; Rappaport, W. D.; Villar, H. V.; Neal, D.; Fleming, S.; Wankel,
A.; Herrington, P. N.; Carmona, R.; Sandberg, A. A.: Cytogenetic
profile of 109 lipomas. Cancer Res. 51: 422-433, 1991.
19. Stephens, F. E.; Isaacson, A.: Hereditary multiple lipomatosis. J.
Hered. 50: 51-53, 1959.
20. Turc-Carel, C.; Dal Cin, P.; Boghosian, L.; Leong, S. P. L.; Sandberg,
A. A.: Breakpoints in benign lipoma may be at 12q13 or 12q14. Cancer
Genet. Cytogenet. 36: 131-135, 1988.
21. Turc-Carel, C.; Dal Cin, P.; Rao, U.; Karakousis, C.; Sandberg,
A. A.: Cytogenetic studies of adipose tissue tumors. I. A benign
lipoma with reciprocal translocation t(3;12)(q28;q14). Cancer Genet.
Cytogenet. 23: 283-289, 1986.
22. Weinberg, J. B.; Hasstedt, S. J.; Skolnick, M. H.; Kimberling,
W. J.; Baty, B.: Analysis of a large pedigree with elliptocytosis,
multiple lipomatosis, and biological false-positive serological tests
for syphilis. Am. J. Med. Genet. 5: 57-67, 1980.
Frequent rearrangements at 12q13 or 12q14
Nara Sobreira - updated: 7/19/2010
Victor A. McKusick - updated: 1/19/2005
Victor A. McKusick: 6/2/1986