Miscellaneous
Prevalence and Clinical Significance of Cardiovascular Abnormalities in Patients With the LEOPARD Syndrome

https://doi.org/10.1016/j.amjcard.2007.03.093Get rights and content

The aim of this study was to characterize cardiovascular involvement in a large number of patients with LEOPARD syndrome. Twenty-six patients (age range 0 to 63 years, median age at the time of the study evaluation 17 years) underwent clinical and genetic investigations. Familial disease was ascertained in 9 patients. Nineteen patients (73%) showed electrocardiographic abnormalities. Left ventricular (LV) hypertrophy was present in 19 patients (73%), including 9 with LV outflow tract obstructions; right ventricular hypertrophy was present in 8 patients (30%). Valve (57%) and coronary artery (15%) anomalies were also observed. Single patients showed LV apical aneurysm, LV noncompaction, isolated LV dilation, and atrioventricular canal defect. During follow-up (9.1 ± 4.5 years), 2 patients died suddenly, and 2 patients had cardiac arrest. These patients had LV hypertrophy. Despite the limited number of subjects studied, genotype-phenotype correlations were observed in familial cases. In conclusion, most patients with LEOPARD syndrome showed LV hypertrophy, often in association with other valvular or congenital defects. A spectrum of underrecognized cardiac anomalies were also observed. Long-term prognosis was benign, but the occurrence of 4 fatal events in patients with LV hypertrophy indicates that such patients require careful risk assessment and, in some cases, consideration for prophylaxis against sudden death.

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Methods

This was an observational study involving 3 Italian centers and 2 centers in the United Kingdom. Twenty-six European-derived patients referred to these institutions since 1990 were enrolled in the study. Informed consent was obtained for all participants according to a protocol proposed by the ethics committee at Monaldi Hospital (Naples, Italy) and approved by the other institutions.

Phenotypical examination for major and minor dysmorphisms was performed by 2 clinical geneticists (MCD, MP).

Results

The study cohort comprised 26 subjects (7 male and 19 female subjects; age range 0 to 63 years, median age at the time of the study evaluation 17 years). The median age at the diagnosis of LS was 13 years (range 0 to 62, 25th percentile 3.25, 75th percentile 18.7). Familial disease was ascertained by the investigators in 9 patients; the others (17 patients [65%]) had sporadic cases. Multiple lentigines (Figure 1) and structural heart defects were the most common features in the 26 patients

Discussion

This is the first systematic analysis of cardiovascular phenotype in large cohort of patients with LS. Since the original description, ECG abnormalities and pulmonary stenosis have been part of the clinical picture of the disease, while LV hypertrophy and other cardiac defects have been successively characterized.1, 2, 3, 15

LV hypertrophy, mainly asymmetric (79%), was the most common cardiac anomaly in our series. Apical and concentric hypertrophy, not previously reported, were observed in our

Acknowledgment

We thank the patients and families who participated in this study.

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This work was supported in part by grants from the Italian Ministry of Health (RC 2004, RC 2005, Rome, Italy). Dr. Dallapiccola was supported by the Italian Ministry of Instruction, University and Research, Rome, Italy.

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