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LEOPARD syndrome (PTPN11, T468M) in three boys fulfilling neurofibromatosis type 1 clinical criteria

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Abstract

Noonan syndrome (NS) and neurofibromatosis type 1 (NF1) are well-defined entities. The association of both disorders is called neurofibromatosis–Noonan syndrome (NFNS), a disorder that has been related to mutations in the NF1 gene. Both NS and NFNS display phenotypic overlapping with LEOPARD syndrome (LS), and differential diagnosis between these two entities often represents a challenge for clinicians. We report on three patients (two brothers and a not-related patient) diagnosed as having NFNS. They fulfilled NF1 diagnostic criteria and had some features of NS. The three of them had hypertophic cardiomyopathy while neurofibromas, Lisch nodules, and unidentified bright objects on MRI were absent. PTPN11 gene assays revealed a T468M mutation, typical of LS. Thorough clinical examinations of the patients revealed multiple lentigines, which were considered to be freckling in the initial evaluation. We conclude that NF1 clinical criteria should be used with caution in patients with features of NS. Patients with hyperpigmented cutaneous spots associated with cardiac anomalies, even if fulfilling the minimal NF1 criteria for diagnosis, should be strongly considered for LS diagnosis.

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Acknowledgments

The authors thank Ronan Kellegher for the revision of the English manuscript and Manuel Jaime from 11th Floor Productions for the artwork. This work was supported in part by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain (project FIS 061179).

Conflict of interest

The authors declare no conflict of financial interest with the organizations that sponsored the research of this article.

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Authors and Affiliations

  1. Pediatrics Department, Hospital Virgen de la Salud, Toledo, Spain

    Atilano Carcavilla

  2. Pediatrics Department, Hospital Severo Ochoa, Leganés, Madrid, Spain

    Isabel Pinto

  3. Molecular Genetics Department, Hospital Gregorio Marañón, Madrid, Spain

    Atilano Carcavilla, Rafael Muñoz-Pacheco & Begoña Ezquieta

  4. Pediatrics Department, Hospital Ramón y Cajal, Madrid, Spain

    Raquel Barrio & Maria Martin-Frías

  5. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III, Madrid, Spain

    Begoña Ezquieta

  6. Avenida Barber, 30, 45004, Toledo, Spain

    Atilano Carcavilla

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  1. Atilano Carcavilla
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  2. Isabel Pinto
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  3. Rafael Muñoz-Pacheco
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Correspondence to Atilano Carcavilla.

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Carcavilla, A., Pinto, I., Muñoz-Pacheco, R. et al. LEOPARD syndrome (PTPN11, T468M) in three boys fulfilling neurofibromatosis type 1 clinical criteria. Eur J Pediatr 170, 1069–1074 (2011). https://doi.org/10.1007/s00431-011-1418-5

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  • DOI: https://doi.org/10.1007/s00431-011-1418-5

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