Medscape is available in 5 Language Editions – Choose your Edition here.


LEOPARD Syndrome Treatment & Management

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
Updated: Jun 22, 2016

Medical Care

Cryosurgery and laser treatment may be beneficial for isolated lentigines; however, because of the large number of lentigines it may be time consuming. For some patients, treatment with tretinoin cream and hydroquinone cream may be helpful.

Therapeutic regimens include beta-adrenergic receptor or calcium channel blocking agents to reduce outflow tract obstruction and adrenergic responsiveness in patients with structural cardiac anomalies.

Antiarrhythmic treatment may be required in cases with life-threatening ventricular ectopy.


Surgical Care

Surgical treatment may be necessary in cases with severe outflow tract obstruction or in patients with cryptorchidism, hypospadias, or severe skeletal deformity.



Genetic counseling should be offered to all patients with LEOPARD syndrome. Frequent presentation of forme fruste requires careful examination of all family members.

Consult a cardiologist, endocrinologist, and orthopedist as dictated by history and physical examination findings.



Advise patients with outflow tract obstruction or significant cardiac dysrhythmias to avoid strenuous physical exercises.



Genetic counseling and examination of other family members is indicated.


Long-Term Monitoring

All patients with the LEOPARD syndrome should undergo periodic cardiac assessment with echocardiography and electrocardiographic examination because the heart conduction impairment tends to occur gradually but progressively.

Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.


Sergiusz Jozwiak, MD, PhD Professor and Head of Pediatric Neurology, Warsaw Medical University, Poland

Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi

Disclosure: Received honoraria from Novartis for speaking and teaching.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD Associate Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

James J Nordlund, MD Professor Emeritus, Department of Dermatology, University of Cincinnati College of Medicine

James J Nordlund, MD is a member of the following medical societies: American Academy of Dermatology, Sigma Xi, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

  1. Kim J, Kim MR, Kim HJ, Lee KA, Lee MG. LEOPARD Syndrome with PTPN11 Gene Mutation Showing Six Cardinal Symptoms of LEOPARD. Ann Dermatol. 2011 May. 23(2):232-5. [Medline]. [Full Text].

  2. Motegi SI, Yokoyama Y, Ogino S, Yamada K, Uchiyama A, Takeuchi Y, et al. Pathogenesis of Multiple Lentigines in LEOPARD Syndrome with PTPN11 Gene Mutation. Acta Derm Venereol. 2015 Apr 28. [Medline].

  3. Noda S, Takahashi A, Hayashi T, Tanuma S, Hatakeyama M. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling. Biochem Biophys Res Commun. 2016 Jan 22. 469 (4):1133-9. [Medline].

  4. Ogata T, Yoshida R. PTPN11 mutations and genotype-phenotype correlations in Noonan and LEOPARD syndromes. Pediatr Endocrinol Rev. 2005 Jun. 2(4):669-74. [Medline].

  5. Hanna N, Montagner A, Lee WH, Miteva M, Vidal M, Vidaud M, et al. Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS Lett. 2006 May 1. 580(10):2477-82. [Medline].

  6. Kontaridis MI, Swanson KD, David FS, Barford D, Neel BG. PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. J Biol Chem. 2006 Mar 10. 281(10):6785-92. [Medline].

  7. Wang Y, Chen C, Wang DW. Leopard syndrome caused by heterozygous missense mutation of Tyr 279 Cys in the PTPN11 gene in a sporadic case of Chinese Han. Int J Cardiol. 2014 Jul 1. 174(3):e101-4. [Medline].

  8. Begic F, Tahirovic H, Kardaševic M, Kalev I, Muru K. Leopard syndrome: a report of five cases from one family in two generations. Eur J Pediatr. 2014 Jun. 173(6):819-22. [Medline].

  9. Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am J Hum Genet. 2006 Feb. 78(2):279-90. [Medline].

  10. Ucar C, Calyskan U, Martini S, Heinritz W. Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive). J Pediatr Hematol Oncol. 2006 Mar. 28(3):123-5. [Medline].

  11. Laux D, Kratz C, Sauerbrey A. Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome. J Pediatr Hematol Oncol. 2008 Aug. 30(8):602-4. [Medline].

  12. Kalidas K, Shaw AC, Crosby AH, Newbury-Ecob R, Greenhalgh L, Temple IK, et al. Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. J Hum Genet. 2005. 50(1):21-5. [Medline].

  13. Writzl K, Hoovers J, Sistermans EA, Hennekam RC. LEOPARD syndrome with partly normal skin and sex chromosome mosaicism. Am J Med Genet A. 2007 Nov 1. 143A(21):2612-5. [Medline].

  14. Voron DA, Hatfield HH, Kalkhoff RK. Multiple lentigines syndrome. Case report and review of the literature. Am J Med. 1976 Mar. 60(3):447-56. [Medline].

  15. Digilio MC, Sarkozy A, de Zorzi A, Pacileo G, Limongelli G, Mingarelli R, et al. LEOPARD syndrome: clinical diagnosis in the first year of life. Am J Med Genet A. 2006 Apr 1. 140(7):740-6. [Medline].

  16. Bujaldon AR. LEOPARD syndrome: what are café noir spots?. Pediatr Dermatol. 2008 Jul-Aug. 25(4):444-8. [Medline].

  17. Xing Q, Chen X, Wang M, Bai W, Peng X, Gao R, et al. A locus for familial generalized lentiginosis without systemic involvement maps to chromosome 4q21.1-q22.3. Hum Genet. 2005 Jul. 117(2-3):154-9. [Medline].

  18. Aragüés IH, Domínguez MC, Blanco VP, Zubicaray BE, Fernández RS. LEOPARD syndrome and multiple granular cell tumors: An underreported association?. Indian J Dermatol Venereol Leprol. 2016 Jan-Feb. 82 (1):77-9. [Medline].

  19. Limongelli G, Sarkozy A, Pacileo G, Calabro P, Digilio MC, Maddaloni V, et al. Genotype-phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome. Am J Med Genet A. 2008 Mar 1. 146A(5):620-8. [Medline].

  20. Limongelli G, Pacileo G, Marino B, Digilio MC, Sarkozy A, Elliott P, et al. Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome. Am J Cardiol. 2007 Aug 15. 100(4):736-41. [Medline].

  21. Yagubyan M, Panneton JM, Lindor NM, Conti E, Sarkozy A, Pizzuti A. LEOPARD syndrome: a new polyaneurysm association and an update on the molecular genetics of the disease. J Vasc Surg. 2004 Apr. 39(4):897-900. [Medline].

  22. Porciello R, Divona L, Strano S, Carbone A, Calvieri C, Giustini S. Leopard syndrome. Dermatol Online J. 2008 Mar 15. 14(3):7. [Medline].

  23. Rudolph G, Haritoglou C, Kalpadakis P, Boergen KP, Meitinger T. [LEOPARD syndrome with iris-retina-choroid coloboma. Discordant findings in monozygotic twins (MIM # 151 100)]. Ophthalmologe. 2001 Nov. 98(11):1101-3. [Medline].

  24. Spatola M, Wider C, Kuntzer T, Croquelois A. PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain. BMC Neurol. 2015 Apr 16. 15:55. [Medline]. [Full Text].

  25. Lodish MB, Stratakis CA. The differential diagnosis of familial lentiginosis syndromes. Fam Cancer. 2011 Sep. 10(3):481-90. [Medline].

  26. Cheng YP, Chiu HY, Hsiao TL, Hsiao CH, Lin CC, Liao YH. Scalp melanoma in a woman with LEOPARD syndrome: possible implication of PTPN11 signaling in melanoma pathogenesis. J Am Acad Dermatol. 2013 Oct. 69(4):e186-7. [Medline].

  27. Jozwiak S, Schwartz RA, Janniger CK. LEOPARD syndrome (cardiocutaneous lentiginosis syndrome). Cutis. 1996 Apr. 57(4):208-14. [Medline].

  28. Jozwiak S, Schwartz RA, Janniger CK, Zaremba J. Familial occurrence of the LEOPARD syndrome. Int J Dermatol. 1998 Jan. 37(1):48-51. [Medline].

Multiple lentigines on the face of a child with LEOPARD syndrome.
Lentigines on the sclerae in a child with LEOPARD syndrome.
Area of disordered pigmentation on the trunk of a patient with LEOPARD syndrome.
Onychodystrophy in a child with LEOPARD syndrome.
Multiple, small lentigines evenly distributed over the trunk of an adult female with LEOPARD syndrome.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.