Familial LEOPARD Syndrome With Hypertrophic Cardiomyopathy

Published on Nov 15, 2020in American Journal of Cardiology2.778
· DOI :10.1016/J.AMJCARD.2020.08.027
Patrycja Galazka2
Estimated H-index: 2
(UW: University of Wisconsin-Madison),
Renuka Jain6
Estimated H-index: 6
(UW: University of Wisconsin-Madison)
+ 6 AuthorsA. Jamil Tajik16
Estimated H-index: 16
(UW: University of Wisconsin-Madison)
Multiple lentigines syndrome is an autosomal dominant inherited condition with variable expressivity that is also known as LEOPARD syndrome. LEOPARD stands for lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary valve stenosis, abnormalities of genitalia, retardation of growth, and deafness. LEOPARD syndrome most frequently develops secondary to a missense mutation of protein-tyrosine phosphatase nonreceptor type 11 gene, which encodes tyrosine phosphatase. The missense mutation p.Tyr279Cys can either occur as a de novo mutation or affect multiple family members. Although hypertrophic cardiomyopathy is not part of the LEOPARD acronym, it is the most frequent cardiac anomaly observed in this syndrome. The recognition of increased left or right ventricular wall thickness in patients with LEOPARD syndrome may have significant impact on their clinical course similar to classic hypertrophic cardiomyopathy, which may require septal reduction procedures for relief of left or right ventricular outflow tract obstruction or implantable cardioverter-defibrillator placement for sudden cardiac death prevention. We describe a case series of a family with diffuse lentigines and hypertrophic cardiomyopathy in which the son carries the protein-tyrosine phosphatase nonreceptor type 11 (p.Tyr279Cys) gene mutation and both the son and daughter underwent left ventricular myectomy at an early age. In conclusion, our case series of a family with LEOPARD syndrome illustrates the importance of recognizing hypertrophic cardiomyopathy as part of this syndrome.
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Abstract Multiple lentigines/LEOPARD syndrome (LS) is a rare, autosomal dominant disorder characterized by Lentigines, Electrocardiogram abnormalities, Ocular hypertelorism, Pulmonic valvular stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness. Like the more common Noonan syndrome (NS), LS is caused by germ line missense mutations in PTPN11, encoding the protein-tyrosine phosphatase Shp2. Enzymologic, structural, cell biological, and mouse genetic studies indicate that NS i...
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