Reed’s Syndrome

  • Kristen Pacific
  • Jason EmerEmail author


Multiple cutaneous and uterine leiomyomatosis (MCUL), also known as Reed’s syndrome, is an autosomal dominant genetic condition. Affected individuals have an increased predisposition to develop benign smooth muscle tumors (leiomyomas) in the skin and uterus. Affected females frequently develop uterine leiomyomas (fibroids) that are larger and more numerous and emerge earlier than those in the general population. Subsets of these patients are at risk for renal cell carcinoma (RCC) and have been determined to have mutations in the fumarate hydratase (FH) gene. In individuals or families without RCC, the syndrome may be referred to as multiple cutaneous leiomyomatosis (MCL) or MCUL. The term hereditary leiomyomatosis and RCC (HLRCC) refers to families with an increased prevalence of smooth muscle tumors and RCC as a result of the FH genetic defect. Since cutaneous leiomyomas are not exceptionally common, their presence—whether single or in multiplicity—should raise suspicion of underlying uterine leiomyomas and the possibility of real disease. Increased clinical awareness is important due to the association between coexisting cutaneous and systemic diseases.


Renal Cell Carcinoma Botulinum Toxin Uterine Fibroid Glomus Tumor Granular Cell Tumor 
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  1. 1.
    Hereditary leiomyomatosis and renal cell cancer. Available at Accessed 18 Sep 2012Google Scholar
  2. 2.
    Reed WB, Walker R, Horowitz R. Cutaneous leiomyomata with uterine leiomyomata. Acta Derm Venereol. 1973;53(5):409–16.PubMedGoogle Scholar
  3. 3.
    Kloepfer HW, Krafchuk J, Derbes V, Burks J. Hereditary multiple leiomyoma of the skin. Am J Hum Genet. 1958;10(1):48–52.PubMedGoogle Scholar
  4. 4.
    Holst VA, Junkins-Hopkins JM, Elenitsas R. Cutaneous smooth muscle neoplasms: clinical features, histologic findings, and treatment options. J Am Acad Dermatol. 2002;46(4): 477–90.PubMedCrossRefGoogle Scholar
  5. 5.
    Costella TM, Romiti N, Almeida JR, et al. Do you know this syndrome? An Bras Dermatol. 2011;86(4):815–24.PubMedCrossRefGoogle Scholar
  6. 6.
    Orellana Diaz O, Hernandez PE. Leiomyoma cutis and leiomyosarcoma: a 10-year study and a short review. J Dermatol Surg Oncol. 1983;9(4):283–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Badeloe S, Frank J. Clinical and molecular genetic aspects of hereditary multiple cutaneous leiomyomatosis. Eur J Dermatol. 2009;19(6):545–51.PubMedGoogle Scholar
  8. 8.
    Malhotra P, Walia H, Singh A, Ramesh V. Leiomyoma cutis: a clinicopathological series of 37 cases. Indian J Dermatol. 2010;55(4):337–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Wei MH, Toure O, Glenn GM, et al. Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet. 2006;43(1):18–27.PubMedCrossRefGoogle Scholar
  10. 10.
    Kiuru M, Launonen V. Hereditary leiomyomatosis and renal cell cancer (HLRCC). Curr Mol Med. 2004;4(8):869–75.PubMedCrossRefGoogle Scholar
  11. 11.
    García Muret MP, Pujol RM, Alomar A, et al. Familial leiomyomatosis cutis et uteri (Reed’s syndrome). Arch Dermatol Res. 1988;280:S29–32.PubMedCrossRefGoogle Scholar
  12. 12.
    Toro JR, Nickerson ML, Wei MH, et al. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet. 2003;73(1):95–106.PubMedCrossRefGoogle Scholar
  13. 13.
    Alam NA, Olpin S, Leigh IM. Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer. Br J Dermatol. 2005;153(1):11–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Tomlinson IP, Alam NA, Rowan AJ, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet. 2002;30(4):406–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Kiuru M, Launonen V, Hietala M, et al. Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology. Am J Pathol. 2001; 159(3):825–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Alam NA, Bevan S, Churchman M, et al. Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3–q43. Am J Hum Genet. 2001;68(5):1264–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Alam NA, Rowan AJ, Wortham NC, et al. Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. Hum Mol Genet. 2003;12(11):1241–52.PubMedCrossRefGoogle Scholar
  18. 18.
    Badeloe S, van Geel M, van Steensel MA, et al. Diffuse and segmental variants of cutaneous leiomyomatosis: novel mutations in the fumarate hydratase gene and review of the literature. Exp Dermatol. 2006;15(9):735–41.PubMedCrossRefGoogle Scholar
  19. 19.
    Sudarshan S, Pinto PA, Neckers L, Linehan WM. Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer—a distinct form of hereditary kidney cancer. Nat Clin Pract Urol. 2007;4(2):104–10.PubMedCrossRefGoogle Scholar
  20. 20.
    Mitchum MD, Adams EG, Holcomb KZ. JAAD Grand Rounds quiz. A 46-year-old man with agminated papules on the buttock. Reed syndrome. J Am Acad Dermatol. 2012;66(2):337–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Smith CG, Glaser DA, Leonardi C. Zosteriform multiple leiomyomas. J Am Acad Dermatol. 1998;38(2 Pt 1):272–3.PubMedCrossRefGoogle Scholar
  22. 22.
    Naverson DN, Trask DM, Watson FH, Burket JM. Painful tumors of the skin: “LEND AN EGG”. J Am Acad Dermatol. 1993;28(2 Pt 2):298–300.CrossRefGoogle Scholar
  23. 23.
    Apatenko AK, Turusov VS. The painful tumours of the skin. Neoplasma. 1968;15(2): 187–202.PubMedGoogle Scholar
  24. 24.
    Lehtonen HJ. Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics. Fam Cancer. 2011;10(2):397–411.PubMedCrossRefGoogle Scholar
  25. 25.
    Kilpatrick SE, Mentzel T, Fletcher CD. Leiomyoma of deep soft tissue. Clinicopathologic analysis of a series. Am J Surg Pathol. 1994;18(6):576–82.PubMedCrossRefGoogle Scholar
  26. 26.
    Spencer JM, Amonette RA. Tumors with smooth muscle differentiation. Dermatol Surg. 1996;22(9):761–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Miettinen M, Lehto VP, Virtanen I. Antibodies to intermediate filament proteins. The differential diagnosis of cutaneous tumors. Arch Dermatol. 1985;121(6):736–41.PubMedCrossRefGoogle Scholar
  28. 28.
    McGinley KM, Bryant S, Kattine AA, et al. Cutaneous leiomyomas lack estrogen and progesterone receptor immunoreactivity. J Cutan Pathol. 1997;24(4):241–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Pithukpakorn M, Toro JR. Hereditary leiomyomatosis and renal cell cancer. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. Genereviews. Seattle, Washington: University of Washington; 1993–2006.Google Scholar
  30. 30.
    Rongioletti F, Fausti V, Ferrando B, et al. A novel missense mutation in fumarate hydratase in an Italian patient with a diffuse variant of cutaneous leiomyomatosis (Reed’s syndrome). Dermatology. 2010;221(4):378–80.PubMedCrossRefGoogle Scholar
  31. 31.
    Fisher WC, Helwig EB. Leiomyomas of the skin. Arch Dermatol. 1963;88:510–20.PubMedCrossRefGoogle Scholar
  32. 32.
    Montgomery H, Winkelmann RK. Smooth-muscle tumors of the skin. AMA Arch Derm. 1959;79(1):32–40.PubMedCrossRefGoogle Scholar
  33. 33.
    George S, Pulimood S, Jacob M, Chandi SM. Pain in multiple leiomyomas alleviated by nifedipine. Pain. 1997;73(1):101–2.PubMedCrossRefGoogle Scholar
  34. 34.
    Thompson JA. Jr Therapy for painful cutaneous leiomyomas. J Am Acad Dermatol. 1985;13(5 Pt 2):865–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Batchelor RJ, Lyon CC, Highet AS. Successful treatment of pain in two patients with cutaneous leiomyomata with the oral alpha-1 adrenoceptor antagonist, doxazosin. Br J Dermatol. 2004;150(4):775–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Thyresson HN, Su WP. Familial cutaneous leiomyomatosis. J Am Acad Dermatol. 1981; 4(4):430–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Haugen RN, Tharp MD. The use of gabapentin for recurrent painful attacks with multiple piloleiomyomas. J Drugs Dermatol. 2008;7(4):401–2.PubMedGoogle Scholar
  38. 38.
    Sifaki MK, Krueger-Krasagakis S, Koutsopoulos A, et al. Botulinum toxin type A-treatment of a patient with multiple cutaneous piloleiomyomas. Dermatology. 2009;218(1):44–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Onder M, Adien E. A new indication of botulinum toxin: leiomyoma-related pain. J Am Acad Dermatol. 2009;60(2):325–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Christenson LJ, Smith K, Arpey CJ. Treatment of multiple cutaneous leiomyomas with CO2 laser ablation. Dermatol Surg. 2000;26(4):319–22.PubMedCrossRefGoogle Scholar
  41. 41.
    Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005;26(5):785–93.PubMedCrossRefGoogle Scholar
  42. 42.
    Aoki KR. Pharmacology and immunology of botulinum toxin type A. Clin Dermatol. 2003; 21(6):476–80.PubMedCrossRefGoogle Scholar
  43. 43.
    Hindley JT, Law PA, Hickey M, et al. Clinical outcomes following percutaneous magnetic resonance image guided laser ablation of symptomatic uterine fibroids. Hum Reprod. 2002; 17(10):2737–41.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of DermatologyMount Sinai School of MedicineNew YorkUSA

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