Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome.
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.
Limongelli
Giuseppe
G
Second University of Naples, Monaldi Hospital, Naples, Italy. limongelligiuseppe@libero.it
Pacileo
Giuseppe
G
Marino
Bruno
B
Digilio
Maria Cristina
MC
Sarkozy
Anna
A
Elliott
Perry
P
Versacci
Paolo
P
Calabro
Paolo
P
De Zorzi
Andrea
A
Di Salvo
Giovanni
G
Syrris
Petros
P
Patton
Michael
M
McKenna
William J
WJ
Dallapiccola
Bruno
B
Calabro
Raffaele
R
D000293:Adolescent; D000328:Adult; D018376:Cardiovascular Abnormalities / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D044542:LEOPARD Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015996:Survival Rate; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; D004247:DNA; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases