Journal of the Formosan Medical Association
Volume 108, Issue 10 , Pages 803-807, October 2009

PTPN11 Mutations in LEOPARD Syndrome: Report of Four Cases in Taiwan

  • I-Shou Lin

      Affiliations

    • Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
    • ,
  • Jieh-Neng Wang

      Affiliations

    • Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
    • ,
  • Sheau-Chiou Chao

      Affiliations

    • Department of Dermatology, National Cheng Kung University Hospital, Tainan, Taiwan
    • ,
  • Jing-Ming Wu

      Affiliations

    • Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
    • ,
  • Shio-Jean Lin

      Affiliations

    • Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Shio-Jean Lin, Department of Pediatrics, National Cheng Kung University Hospital, 138 Sheng Li Road, Tainan 704, Taiwan

Received 17 November 2008; received in revised form 6 February 2009; accepted 10 April 2009.

Article Outline

Background/Purpose

LEOPARD syndrome (LS) is a rare, autosomal dominant disorder. The typical clinical presentation includes multiple lentigines and cardiac defects. Mutation analysis of the PTPN11 gene is feasible. We report four cases of LS, which were confirmed by molecular genetic study.

Methods

The clinical features and mutations of the four patients were summarized.

Results

The diagnosis of all four patients was made when lentigines appeared during childhood. Three cases had hypertrophic cardiomyopathy. No electrocardiographic conduction abnormality was noted in any of the cases. Three patients had hypertelorism and three had short stature. Two patients, identical twins, presented with the atypical phenotype of tongue protrusion and hepatosplenomegaly at birth. Twin B had mild mental retardation. Case 4 had moderate hearing impairment. Point mutation of the PTPN11 gene was found in all patients.

Conclusion

LS has typical skin manifestations. All patients should undergo a comprehensive examination, especially echocardiography and electrocardiography. The diagnosis can be confirmed by genetic study.

Key Words:  hypertrophic cardiomyopathy , LEOPARD syndrome , mutation , PTPN11 protein

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Gorlin RJ , Anderson RC , Blaw M . Multiple lentigines syndrome . Am J Dis Child . 1969;117:652–662
  2. Voron DA , Hatfield HH , Kalkhoff RK . Multiple lentigines syndrome. Case report and review of the literature . Am J Med . 1976;60:447–456
  3. Gorlin RJ , Cohen MM , Hennekam RCM . Syndromes of the Head and Neck . New York: Oxford University Press; 2001;
  4. Keren B , Hadchouel A , Saba S , et al.   PTPN11 mutations in patients with LEOPARD syndrome: a French multicentric experience . J Med Genet . 2004;41:e117
  5. Sarkozy A , Conti E , Digilio MC , et al.   Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome . J Med Genet . 2004;41:e68
  6. Digilio MC , Conti E , Sarkozy A , et al.   Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene . Am J Hum Genet . 2002;71:389–394
  7. Legius E , Schrander-Stumpel C , Schollen E , et al.   PTPN11 mutations in LEOPARD syndrome . J Med Genet . 2002;39:571–574
  8. Digilio MC , Sarkozy A , de Zorzi A , et al.   LEOPARD syndrome: clinical diagnosis in the first year of life . Am J Med Genet A . 2006;140:740–746
  9. Jozwiak S , Schwartz RA , Janniger CK , et al.   Familial occurrence of the LEOPARD syndrome . Int J Dermatol . 1998;37:48–51
  10. Woywodt A , Welzel J , Haase H , et al.   Cardiomyopathic lentiginosis/LEOPARD syndrome presenting as sudden cardiac arrest . Chest . 1998;113:1415–1417
  11. Limongelli G , Pacileo G , Calabro R . Is sudden cardiac death predictable in LEOPARD syndrome? . Cardiol Young . 2006;16:599–601
  12. Chong WS , Klanwarin W , Giam YC . Generalized lentiginosis in two children lacking systemic associations: case report and review of the literature . Pediatr Dermatol . 2004;21:139–145
  13. Colomb D , Morel JP . Multiple lentigines syndrome. Apropos of 2 cases. Critical study of the leopard syndrome . Ann Dermatol Venereol . 1984;111:371–381 [In French]
  14. Tartaglia M , Martinelli S , Stella L , et al.   Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease . Am J Hum Genet . 2006;78:279–290
  15. Tartaglia M , Niemeyer CM , Fragale A , et al.   Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia . Nat Genet . 2003;34:148–150

PII: S0929-6646(09)60408-3

doi:10.1016/S0929-6646(09)60408-3

Journal of the Formosan Medical Association
Volume 108, Issue 10 , Pages 803-807, October 2009

Article Tools