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Entry: 151900
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MIM Entry: 151900
Title:
  %151900 LIPOMATOSIS, MULTIPLE
  ;;LIPOMATOSIS, FAMILIAL MULTIPLE; FML;;
  LIPOMA; LIPO
Text:
  
  DESCRIPTION
  
  Familial multiple lipomatosis is a rare autosomal dominant disorder
  characterized by numerous encapsulated lipomas on the trunk and
  extremities (Keskin et al., 2002).
  
  CLINICAL FEATURES
  
  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.
  
  INHERITANCE
  
  Keskin et al. (2002) reported multiple lipomas in 8 members of 3
  generations of a family with male-to-male transmission.
  
  CYTOGENETICS
  
  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.
  
See Also:
  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)
References:
  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,
  1988.
  
  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:
  1054-1059, 1959.
  
  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,
  2005.
  
  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.
  
Clinical Synopsis:
  
  Skin:
     Lipomatosis
  
  Lab:
     Frequent rearrangements at 12q13 or 12q14
  
  Inheritance:
     Autosomal dominant
  
Contributors: 
  Nara Sobreira - updated: 7/19/2010
  Victor A. McKusick - updated: 1/19/2005
  
Creation Date: 
  Victor A. McKusick: 6/2/1986
  
Edit Dates: 
  terry: 08/06/2010
  carol: 7/19/2010
  tkritzer: 1/21/2005
  terry: 1/19/2005
  joanna: 3/18/2004
  carol: 7/8/2002
  alopez: 6/2/1997
  mark: 10/9/1995
  mimadm: 11/5/1994
  carol: 3/28/1994
  carol: 7/13/1993
  carol: 6/21/1993
  carol: 6/10/1993
  
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