eMedicine Specialties > Dermatology > Internal Medicine

LEOPARD Syndrome: Treatment & Medication

Author: Sergiusz Jozwiak, MD, PhD, Head, Professor, Department of Child Neurology, The Children's Memorial Health Institute of Warsaw, Poland
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Jan 7, 2009

Treatment

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.

Consultations

  • 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.

Activity

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

Medication

The combination of tretinoin and hydroquinone can be used as a skin lightening agent.

Retinoids

Decrease cohesiveness of abnormal hyperproliferative keratinocytes and may reduce potential for malignant degeneration. Modulate keratinocyte differentiation. Have been shown to reduce risk of skin cancer formation in renal transplant patients. In this case, the combination with hydroquinone is good for topical use.


Tretinoin (Avita, Retin-A)

Keratolytic agent. Acts by increasing epidermal cell mitosis and turnover while suppressing keratin synthesis. May help lighten lentigines, particularly when used in combination with hydroquinone.

Adult

Apply 0.1% cream qhs; hydroquinone cream may be applied afterwards

Pediatric

Not established

Irritation increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose, mouth or eyes (may cause excessive irritation); adverse effects include crusting, severe burning or redness, and swelling of skin

Depigmenting agents

Blocks melanogenesis and works well in combination with tretinoin.


Hydroquinone USP 4%

Lightens hyperpigmented skin by inhibiting enzymatic oxidation of tyrosine and suppressing other melanocyte metabolic processes, thereby further inhibiting melanogenesis. Exposure to sun reverses effects and causes repigmentation.

Adult

Apply to affected areas bid (may be applied after tretinoin application)

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Concurrent use of hydrogen peroxide inactivates hydroquinone, which is labile in the presence of oxygen.

Documented hypersensitivity to drug or related products

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include erythema, stinging, irritation, sensitization, and contact dermatitis in sensitive individuals; application area should not exceed that of face, neck, hands, or arms.

More on LEOPARD Syndrome

Overview: LEOPARD Syndrome
Differential Diagnoses & Workup: LEOPARD Syndrome
Treatment & Medication: LEOPARD Syndrome
Follow-up: LEOPARD Syndrome
Multimedia: LEOPARD Syndrome
References
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References

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

  2. 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. May 1 2006;580(10):2477-82. [Medline].

  3. 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. Mar 10 2006;281(10):6785-92. [Medline].

  4. 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. Feb 2006;78(2):279-90. [Medline].

  5. 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. Mar 2006;28(3):123-5. [Medline].

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

  7. 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].

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

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

  10. 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. Apr 1 2006;140(7):740-6. [Medline].

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

  12. 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. Jul 2005;117(2-3):154-9. [Medline].

  13. 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. Mar 1 2008;146A(5):620-8. [Medline].

  14. 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. Aug 15 2007;100(4):736-41. [Medline].

  15. 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. Apr 2004;39(4):897-900. [Medline].

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

  17. 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. Nov 2001;98(11):1101-3. [Medline].

  18. Ahlbom BE, Dahl N, Zetterqvist P, Anneren G. Noonan syndrome with cafe-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus. Clin Genet. Aug 1995;48(2):85-9. [Medline].

  19. Arnsmeier SL, Paller AS. Pigmentary anomalies in the multiple lentigines syndrome: Is it distinct from LEOPARD syndrome?. Pediatr Dermatol. Mar-Apr 1996;13(2):100-4. [Medline].

  20. Bonioli E, Di Stefano A, Costabel S, Bellini C. Partial agenesis of corpus callosum in LEOPARD syndrome. Int J Dermatol. Nov 1999;38(11):855-62. [Medline].

  21. Cetinkaya E, Gunal N, Sonmez N, Aycan Z, Vidinlisan S, Kahramanyol O, et al. LEOPARD syndrome and hypertrophic obstructive cardiomyopathy: a case report. Turk J Pediatr. Oct-Dec 2004;46(4):373-6. [Medline].

  22. Chan HH, Fung WK, Ying SY, Kono T. An in vivo trial comparing the use of different types of 532 nm Nd:YAG lasers in the treatment of facial lentigines in Oriental patients. Dermatol Surg. Aug 2000;26(8):743-9. [Medline].

  23. Choi WW, Yoo JY, Park KC, Kim KH. LEOPARD syndrome with a new association of congenital corneal tumor, choristoma. Pediatr Dermatol. Mar-Apr 2003;20(2):158-60. [Medline].

  24. Chong WS, Klanwarin W, Giam YC. Generalized lentiginosis in two children lacking systemic associations: case report and review of the literature. Pediatr Dermatol. Mar-Apr 2004;21(2):139-45. [Medline].

  25. Conti E, Dottorini T, Sarkozy A, Tiller GE, Esposito G, Pizzuti A, et al. A novel PTPN11 mutation in LEOPARD syndrome. Hum Mutat. Jun 2003;21(6):654. [Medline].

  26. Coppin BD, Temple IK. Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis). J Med Genet. Jul 1997;34(7):582-6. [Medline].

  27. Dacey MJ, Kulp-Shorten CL, Callen JP. LEOPARD syndrome in a patient with morphea and acro-osteolysis. J Cutan Med Surg. Jul 1998;3(1):25-8. [Medline].

  28. Digilio MC, Capolino R, Marino B, Sarkozy A, Dallapiccola B. Congenital intrahepatic portosystemic venous shunt: an unusual feature in LEOPARD syndrome and in neurofibromatosis type 1. Am J Med Genet A. May 1 2005;134(4):457-8. [Medline].

  29. Digilio MC, Conti E, Sarkozy A, Mingarelli R, Dottorini T, Marino B, et al. Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. Am J Hum Genet. Aug 2002;71(2):389-94. [Medline].

  30. Digilio MC, Pacileo G, Sarkozy A, Limongelli G, Conti E, Cerrato F, et al. Familial aggregation of genetically heterogeneous hypertrophic cardiomyopathy: a boy with LEOPARD syndrome due to PTPN11 mutation and his nonsyndromic father lacking PTPN11 mutations. Birth Defects Res A Clin Mol Teratol. Feb 2004;70(2):95-8. [Medline].

  31. Froster UG, Glander HJ, Heinritz W. [Molecular genetic mutation analysis of the PTPN11 gene in the multiple lentigines (LEOPARD) syndrome]. Hautarzt. Dec 2003;54(12):1190-2. [Medline].

  32. Goyal SB, Aragam JR. Aortic root dilatation with redundancy of mitral and aortic leaflets associated with the LEOPARD syndrome. Int J Cardiol. Jun 7 2006;110(1):110-1. [Medline].

  33. Gupta P, Loiwal V, Rai R, Baruah MC, Mishra K, Krishna A. Leopard syndrome: a tropical rarity. J Dermatol. May 1998;25(5):341-3. [Medline].

  34. Hagspiel KD, Candinas RC, Hagspiel HJ, Amann FW. LEOPARD syndrome: cardiac imaging findings. AJR Am J Roentgenol. Mar 2005;184(3 Suppl):S21-4. [Medline].

  35. Ishigami T, Wakamatsu A, Kishida T, Yokoyama K, Sugiyama K. [ECG changes during emergence from anesthesia in a patient with LEOPARD syndrome]. Masui. Oct 2003;52(10):1115-7. [Medline].

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

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

  38. Keren B, Hadchouel A, Saba S, Sznajer Y, Bonneau D, Leheup B, et al. PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience. J Med Genet. Nov 2004;41(11):e117. [Medline].

  39. Kontoes PP, Vlachos SP, Marayiannis KV. Intense pulsed light for the treatment of lentigines in LEOPARD syndrome. Br J Plast Surg. Sep 2003;56(6):607-10. [Medline].

  40. Legius E, Schrander-Stumpel C, Schollen E, Pulles-Heintzberger C, Gewillig M, Fryns JP. PTPN11 mutations in LEOPARD syndrome. J Med Genet. Aug 2002;39(8):571-4. [Medline].

  41. Merks JH, Caron HN, Hennekam RC. High incidence of malformation syndromes in a series of 1,073 children with cancer. Am J Med Genet A. Apr 15 2005;134A(2):132-43. [Medline].

  42. Munshi A, Munshi AK. Leopard syndrome--report of a variant case. J Indian Soc Pedod Prev Dent. Mar 1999;17(1):5-8. [Medline].

  43. National Center for Biotechnology Information. Online Mendelian Inheritance in Man. Available at http://www.ncbi.nlm.nih.gov/omim/.

  44. Ohkura T, Ohnishi Y, Kawada A, Tajima S, Ishibashi A, Ono K. Leopard syndrome associated with hyperelastic skin: analysis of collagen metabolism in cultured skin fibroblasts. Dermatology. 1999;198(4):385-7. [Medline].

  45. Pacheco TR, Oreskovich N, Fain P. Genetic heterogeneity in the multiple lentigines/LEOPARD/Noonan syndromes. Am J Med Genet A. Jun 15 2004;127A(3):324-6. [Medline].

  46. Peter JR, Kemp JS. LEOPARD syndrome: death because of chronic respiratory insufficiency. Am J Med Genet. Nov 1990;37(3):340-1. [Medline].

  47. Petter G, Rytter M, Haustein UF. [Multiple lentigines (LEOPARD) syndrome. Case reports and review of the literature]. Hautarzt. Jun 2002;53(6):403-8. [Medline].

  48. Robain A, Perchet H, Fuhrman C. Flecainide-associated pneumonitis with acute respiratory failure in a patient with the LEOPARD syndrome. Acta Cardiol. Feb 2000;55(1):45-7. [Medline].

  49. Sarkozy A, Conti E, Digilio MC, Marino B, Morini E, Pacileo G, et al. Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. J Med Genet. May 2004;41(5):e68. [Medline].

  50. Sarkozy A, Obregon MG, Conti E, Esposito G, Mingarelli R, Pizzuti A, et al. A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. Eur J Hum Genet. Dec 2004;12(12):1069-72. [Medline].

  51. Schepis C, Greco D, Siragusa M, Batolo D, Romano C. An intriguing case of LEOPARD syndrome. Pediatr Dermatol. Mar-Apr 1998;15(2):125-8. [Medline].

  52. Shamsadini S, Abazardi H, Shamsadini F. Leopard syndrome. Lancet. Oct 30 1999;354(9189):1530. [Medline].

  53. Shibusawa Y, Tamura A, Mochiki E, Kamisaka K, Kimura H, Ishikawa O. c-kit Mutation in generalized lentigines associated with gastrointestinal stromal tumor. Dermatology. 2004;208(3):217-20. [Medline].

  54. Tartaglia M, Gelb BD. Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet. 2005;6:45-68. [Medline].

  55. Ton'sheva LN, Sidorova LD. [The Leopard syndrome in a patient with sebocystomatosis]. Klin Med (Mosk). 2001;79(6):65-7. [Medline].

  56. Tong KL, Ding ZP, Chua T. Leopard syndrome. Singapore Med J. Jul 2001;42(7):328-31. [Medline].

  57. Torres J, Russo P, Tobias JD. Anaesthetic implications of LEOPARD syndrome. Paediatr Anaesth. Apr 2004;14(4):352-6. [Medline].

  58. Tullu MS, Muranjan MN, Kantharia VC, Parmar RC, Sahu DR, Bavdekar SB, et al. Neurofibromatosis-Noonan syndrome or LEOPARD Syndrome? A clinical dilemma. J Postgrad Med. Apr-Jun 2000;46(2):98-100. [Medline].

  59. Wu R, Legius E, Robberecht W, Dumoulin M, Cassiman JJ, Fryns JP. Neurofibromatosis type I gene mutation in a patient with features of LEOPARD syndrome. Hum Mutat. 1996;8(1):51-6. [Medline].

  60. Yam AA, Faye M, Kane A, Diop F, Coulybaly-Ba D, Tamba-Ba A, et al. Oro-dental and craniofacial anomalies in LEOPARD syndrome. Oral Dis. May 2001;7(3):200-2. [Medline].

  61. Yoshida R, Nagai T, Hasegawa T, Kinoshita E, Tanaka T, Ogata T. Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome. Am J Med Genet A. Nov 1 2004;130A(4):432-4. [Medline].

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Further Reading

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Keywords

LEOPARD syndrome, cardiocutaneous lentiginosis syndrome, multiple lentigines syndrome, generalized lentiginosis, centrofacial lentiginosis, lentiginosis profusa syndrome, lentiginosis-deafness-cardiopathy syndrome, cardiocutaneous syndrome, progressive cardiomyopathic lentiginosis, Moynahan syndrome, OMIM 151100

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Contributor Information and Disclosures

Author

Sergiusz Jozwiak, MD, PhD, Head, Professor, Department of Child Neurology, The Children's Memorial Health Institute of Warsaw, Poland
Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

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, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University 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, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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