LEOPARD Syndrome Workup

1. Denny JW, Krishna S, Valiallah N, Fogo A, Natkunarajah J. Images of the month 2: A leopard never changes its spots. Clin Med (Lond). 2020 Mar. 20 (2):231-232. [QxMD MEDLINE Link].

2. Li R, Baskfield A, Lin Y, Beers J, Zou J, Liu C, et al. Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p.Q510P mutation in the PTPN11 gene. Stem Cell Res. 2019 Jan. 34:101374. [QxMD MEDLINE Link].

3. Alfurayh N, Alsaif F, Alballa N, Zeitouni L, Ramzan K, Imtiaz F, et al. LEOPARD Syndrome with PTPN11 Gene Mutation in Three Family Members Presenting with Different Phenotypes. J Pediatr Genet. 2020 Dec. 9 (4):246-251. [QxMD MEDLINE Link].

4. Duat-Rodriguez A, Hernandez-Martin A. [Update on the treatment of RASopathies]. Rev Neurol. 2017 May 17. 64 (s03):S13-S17. [QxMD MEDLINE Link].

5. 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. [QxMD MEDLINE Link]. [Full Text].

6. 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. [QxMD MEDLINE Link].

7. Wu J, Zhang H, Zhao G, Wang R. Allosteric inhibitors of SHP2: an updated patent review (2015-2020). Curr Med Chem. 2020 Sep 28. [QxMD MEDLINE Link].

8. 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. [QxMD MEDLINE Link].

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

10. 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. [QxMD MEDLINE Link].

11. 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. [QxMD MEDLINE Link].

12. 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. [QxMD MEDLINE Link].

13. 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. [QxMD MEDLINE Link].

14. 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. [QxMD MEDLINE Link].

15. 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. [QxMD MEDLINE Link].

16. 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. [QxMD MEDLINE Link].

17. 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. [QxMD MEDLINE Link].

18. 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. [QxMD MEDLINE Link].

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

20. 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. [QxMD MEDLINE Link].

21. Lee CL, Tan LTH, Lin HY, Hwu WL, Lee NC, Chien YH, et al. Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan. Am J Med Genet A. 2020 Feb. 182 (2):357-364. [QxMD MEDLINE Link].

22. 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. [QxMD MEDLINE Link].

23. Jurko T, Jurko A Jr, Krsiakova J, Jurko A, Minarik M, Mestanik M. Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy. Acta Clin Belg. 2018 May 2. 1-4. [QxMD MEDLINE Link].

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

25. 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. [QxMD MEDLINE Link].

26. 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. [QxMD MEDLINE Link].

27. 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. [QxMD MEDLINE Link].

28. 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. [QxMD MEDLINE Link].

29. Nakagama Y, Inuzuka R, Ichimura K, Hinata M, Takehara H, Takeda N, et al. Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy. Circ Heart Fail. 2018 Apr. 11 (4):e004660. [QxMD MEDLINE Link].

30. 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. [QxMD MEDLINE Link].

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

32. 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. [QxMD MEDLINE Link].

33. 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. [QxMD MEDLINE Link]. [Full Text].

34. García-Gil MF, Álvarez-Salafranca M, Valero-Torres A, Ara-Martín M. Melanoma in Noonan Syndrome With Multiple Lentigines (Leopard Syndrome): A New Case. Actas Dermosifiliogr. 2020 Sep. 111 (7):619-621. [QxMD MEDLINE Link].

35. 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. [QxMD MEDLINE Link].

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

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

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

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

Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

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.

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: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

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, The Scientific Research Honor Society, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

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