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)
Sources
Abstract
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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References14
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#1Edina NemesH-Index: 1
#2Katalin Farkas (University of Szeged)H-Index: 19
Last. Márta Széll (University of Szeged)H-Index: 19
view all 10 authors...
LEOPARD syndrome (LS, OMIM 151100) is a rare monogenic disorder. The name is an acronym of its major features such as multiple lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth and sensorineural deafness. LS develops due to mutations in the protein-tyrosine phosphatase nonreceptor-type 11, PTPN11. Here, we have investigated a 51-year-old Hungarian male patient affected by LS. Direct sequencing of the P...
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#1Atilano Carcavilla (Hospital General Universitario Gregorio Marañón)H-Index: 6
#2José L. Santomé (Hospital General Universitario Gregorio Marañón)H-Index: 4
Last. Begoña EzquietaH-Index: 13
view all 8 authors...
A B S T R A C T Introduction and objectives: LEOPARD syndrome is an autosomal dominant condition related to Noonan syndrome, although it occurs less frequently. The aim of this study was to characterize the clinical and molecular features of a large series of LEOPARD syndrome patients. Methods: We collected clinical data from 19 patients in 10 hospitals. Bidirectional sequencing analysis of PTPN11, RAF1, and BRAF focused on exons carrying recurrent mutations. Results: After facial dysmorphism, s...
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#1Atilano CarcavillaH-Index: 6
#2José L. Santomé (Hospital General Universitario Gregorio Marañón)H-Index: 4
Last. Begoña Ezquieta (Hospital General Universitario Gregorio Marañón)H-Index: 13
view all 8 authors...
Resumen Introduccion y objetivos El sindrome LEOPARD es una enfermedad autosomica dominante relacionada con el sindrome de Noonan, aunque menos conocida. El objetivo del presente estudio es describir las caracteristicas clinicas y moleculares de una serie amplia de pacientes con sindrome LEOPARD. Metodos Se obtuvieron datos clinicos de 19 pacientes procedentes de 10 hospitales. Se estudiaron los genes PTPN11, RAF1 y BRAF mediante secuenciacion bidireccional de los exones mas recurrentes. Resulta...
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The RAS/MAPK pathway proteins with germline mutations in their respective genes are associated with some disorders such as Noonan, LEOPARD (LS), neurofibromatosis type 1, Costello and cardio-facio-cutaneous syndromes. LEOPARD is an acronym, mnemonic for the major manifestations of this disorder, characterized by multiple lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. Though it is not ...
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#1Madhusudan Ganigara (Madras Medical Mission)H-Index: 6
#2Atul Prabhu (Madras Medical Mission)H-Index: 4
Last. Raghvannair Suresh Kumar (Madras Medical Mission)H-Index: 1
view all 3 authors...
In LEOPARD syndrome, mutations affecting exon 13 of the PTPN11 gene have been correlated with a rapidly progressive severe biventricular obstructive hypertrophic cardiomyopathy (HCM). This is a report of early onset severe HCM in an infant with LEOPARD syndrome and an unusual mutation in exon 13, showing genotype-phenotype correlation.
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#1Giuseppe Limongelli (Seconda Università degli Studi di Napoli)H-Index: 58
#2Anna Sarkozy (Sapienza University of Rome)H-Index: 26
Last. Raffaele Calabrò (Seconda Università degli Studi di Napoli)H-Index: 69
view all 12 authors...
Because it is unclear whether the genotype may influence the clinical course in patients with LEOPARD syndrome (LS), we analyzed clinical and molecular predictors of adverse cardiac events in patients with left ventricular hypertrophy (LVH). A comprehensive cardiovascular evaluation, including baseline electrocardiogram, echocardiography, exercise test and 24 hr Holter monitoring at the time of clinical diagnosis and during follow-up was conducted on 24 patients referred to our departments. Phen...
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#1Maria I. Kontaridis (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 21
#2Kenneth D. SwansonH-Index: 24
Last. Benjamin G. NeelH-Index: 122
view all 5 authors...
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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#1Anna SarkozyH-Index: 26
#2Emanuela Conti (Casa Sollievo della Sofferenza)H-Index: 17
Last. Bruno DallapiccolaH-Index: 108
view all 10 authors...
Multiple lentigines LEOPARD syndrome (MIM 151100) is an autosomal dominant multiple congenital anomaly syndrome, with high penetrance and markedly variable expression.1 The acronym LEOPARD was coined by Gorlin et al. in 1971 as a mnemonic of the major features of this disorder: multiple l entigines, E CG conduction abnormalities, o cular hypertelorism, p ulmonic stenosis, a bnormal genitalia, r etardation of growth, and sensorineural d eafness.2 It is also known as cardiocutaneous syndrome, Moyn...
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#1Marco Tartaglia (ISS: Istituto Superiore di Sanità)H-Index: 68
#2Ernest L. Mehler (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 20
Last. Bruce D. Gelb (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 84
view all 14 authors...
Mutations in PTPN11 , encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome
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#1B D Coppin (Princess Anne Hospital)H-Index: 1
#2I K TempleH-Index: 1
The multiple lentigines syndrome is an autosomal dominant condition which has many similarities to Noonan syndrome, except in the most striking feature from which its name is derived. The less neutral but very apt mnemonic, LEOPARD syndrome, was first used by Gorlin et al to whom the major debt in the definition of this syndrome lies, that is, Lentigines, ECG abnormalities, Ocular hypertelorism/Obstructive cardiomyopathy, Pulmonary valve stenosis, Abnormalities of genitalia in males, Retardation...
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