Original articleLEOPARD Syndrome: A Variant of Noonan Syndrome Strongly Associated With Hypertrophic CardiomyopathySíndrome LEOPARD: una variante del síndrome de Noonan con fuerte asociación a miocardiopatía hipertrófica
Section snippets
INTRODUCTION
LEOPARD syndrome (LS), or Noonan syndrome (NS) with multiple lentigines (OMIM 151100), is an autosomal dominant disorder characterized by multiple lentigines or café au lait spots, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis or hypertrophic cardiomyopathy, genital abnormalities, constitutional growth delay, and deafness.1 LS shares many features with NS (OMIM 163950), which is characterized by an association with congenital heart disease, short stature,
Clinical Evaluation
Patients were evaluated by clinical geneticists and pediatric cardiologists or endocrinologists involved in a Spanish multicenter study of genotype-phenotype relationships, and were diagnosed with LS using the criteria described by Voron et al.12 Blood samples or patient DNA were sent to our center from participating hospitals by the attending clinicians, who had previously obtained informed consent from patients. An initial clinical evaluation based on the preanalytical questionnaire described
RESULTS
The study included 19 patients (13 men, 6 women; age at diagnosis, 11 months to 49 years; mean age, 7.4 years). Cases were referred from 9 hospitals in 5 Spanish regions and 1 hospital in Belgrade (Serbia). Five patients were identified as familial cases (families A and B; 26% of cases; 95% confidence interval [95%CI], 9.1%-51.2%), and the rest were considered sporadic. Table 1 summarizes the phenotypic and molecular findings. Of the total, 15 met Voron's clinical criteria and 4 were considered
DISCUSSION
As some authors have suggested, a classification of cardiomyopathies that takes into account their underlying molecular characteristics could contribute to more appropriate management.19 In the case of hypertrophic cardiomyopathy, the relevance of both NS and LS should be borne in mind.20 This is particularly true when, from a cardiological perspective, the accompanying phenotype can vary from fatal cases to completely asymptomatic patients. Only a high level of suspicion will allow the
CONCLUSIONS
Pulmonary valve stenosis and particularly hypertrophic cardiomyopathy are cardiological findings which may provide the key to identifying the syndrome. Given the potential clinical implications of hypertrophic cardiomyopathy, patients within the clinical spectrum of NS and particularly those with LS should be actively evaluated for this disease. The criteria originally described by Voron et al. in 1976 are still helpful in classifying these patients in terms of diagnosis. Nevertheless, the
FUNDING
Fondo de Investigaciones Sanitarias (PI 06/1179).
CONFLICTS OF INTEREST
None declared.
Acknowledgements
The authors would like to thank the patients and their families for collaborating on the study as well as the clinicians who could not be included as authors. They include Drs. López-Siguero (Hospital Carlos Haya, Málaga), Barrio, and García-Sagredo (Hospital Ramón y Cajal, Madrid), Kuburovic (Mother and Child Healthcare Institute, Serbia), Gracia (Hospital Universitario La Paz, Madrid), Gener Querol (Hospital Universitario de Cruces, Barakaldo, Vizcaya), González-Meneses (Hospital Virgen del
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