Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy (original) (raw)
Related papers
Biventricular Hypertrophic Cardiomyopathy in a Child with LEOPARD Syndrome: a Case Report
Journal of Interdisciplinary Medicine
Background:LEOPARD syndrome is a complex dysmorphogenetic disorder of inconstant penetrance and various morphologic expressions. The syndrome is an autosomal dominant disease that features multiple lentigines, electrocardiographic changes, eye hypertelorism, pulmonary valve stenosis or hypertrophic cardiomyopathy, genital malformations, and a delayed constitutional growth hearing loss, which can be associated with rapidly progressive severe biventricular obstructive hypertrophic cardiomyopathy. No epidemiologic data are available on the real incidence of LEOPARD syndrome; however, this seems to be a rare disease, being often underdiagnosed, as many of its features are mild.Case presentation:We report the case of a 10-year-old female pediatric patient, diagnosed with obstructive hypertrophic cardiomyopathy at the age of 3 months, and recently diagnosed with LEOPARD syndrome. The patient first presented for a cardiologic examination at the age of 3 months, due to a murmur. She present...
Severe, early onset hypertrophic cardiomyopathy in a family with LEOPARD syndrome
Journal of prenatal medicine, 2008
Leopard syndrome is an acronym (multiple Lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) describing an autosomal dominant disease due to mutations in the raS-MapK pathway. Here, we describe a family (mother and daughter) with clinical and molecular diagnosis of Leopard syndrome 1 and HCM, and we report the prenatal diagnosis of HCM in a fetus at risk for Leopard syndrome. An echocardiography was conducted showing a significant hypertrophy of both ventricles (left and right ventricular wall thickness 9mm and 3 mm). After a multidisciplinary counseling the couple opted for the termination of pregnancy Further genotype-phenotype studies are warranted to fully elucidate the impact of the genotype on the natural history of patients with LS and LVH.
American Journal of Cardiology, 2007
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.
A Case of Lentiginosis Associated with LEOPARD Syndrome
2018
Noonan Syndrome with multiple lentigines (formerly called LEOPARD syndrome) is a rare hereditary disorder. It is mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, Electrocardiogram (ECG) conduction abnormalities, Ocular hypertension, Pulmonic stenosis, Abnormal genitalia, of growth Retardation and sensorineural Deafness. We report the case of 4-year-old boy with LEOPARD syndrome, diagnosed clinically and confirmed by molecular technology. Physical examination revealed short stature, multiple lentigines on the head and upper trunk, pectus carinatum and a systolic murmur in mitral area. Echocardiogram revealed Pulmonary Stenosis (PS), Atrial Septal Defect (ASD) and hypertrophic cardiomyopathy. Hearing test screening was normal. He has met the clinical criteria for LEOPARD syndrome. A pathogenic variant of the PTPN11 gene was detected using molecular analysis for confirming the diagnosis. He has been treated with propranolol. The prognosis of LEOPARD syndrome is determined mainly by the severity of cardiac defects, which is also the most common cause of mortality. Early diagnosis and intervention with a multidisciplinary team could decrease mortality, allowing patients to have a normal life. Genetic counseling is recommended for prenatal screening.
Circulation: Heart Failure, 2018
EOPARD syndrome (LS) is a form of RASopathy caused by mutations in the PTPN11 gene an upstream regulator of RAS/MAPK signaling. Although hypertrophic cardiomyopathy (HCM) is a shared cardiac phenotype among RASopathies, HCM complicating patients with LS is characteristic for its unique early-onset and progressive features. We herein report a neonate with LS who presented with an extremely severe form of HCM. Autopsy revealed remarkable evidence of active cardiomyocyte proliferation contributing to the overt cardiomegaly. The case suggests an intriguing association between the observed dramatic increase in cardiomyocyte mitotic activity and the fatal clinical course of LS-associated HCM. CASE PRESENTATION The patient was the second daughter born to nonconsanguineous parents with no significant family history. Marked biventricular hypertrophy was noted on fetal echocardiography at the 28th week of gestation. After an uneventful delivery, the patient was immediately admitted to the neonatal intensive care unit. Physical examination at birth revealed multiple dysmorphic features, including a wide forehead, low set ears, hypertelorism, and wide set nipples. No skin lesions, such as café-au-lait spots or lentigines, were noticed, whereas mild hearing loss was detected by newborn screening. The findings were suggestive of LS. Imaging studies were remarkable for cardiomegaly (Figure [A]), and echocardiogram showed severe ventricular wall thickening (Z score of >5). Elevation of plasma brain natriuretic peptide levels accompanied clinical deterioration, rising from 1993 pg/mL at day 1 up to 7314 pg/mL at day 13. Outflow tract obstructions were severe and progressive, the estimated pressure gradients exceeding 50 mm Hg at day 16. Despite medical therapy with β-blockers and diuretics, she developed progressive cardiac failure and deceased at day 29. Sequencing of the patient's genomic DNA identified a Gly464Ala mutation in exon 12 of the PTPN11 gene, a previously well-described loss-of-function mutation, 1 establishing the molecular diagnosis of LS. Parental sequencing confirmed the de novo origin of the mutation. Autopsy examinations revealed multiple hallmark features of HCM, such as concentric hypertrophy, myocardial thickening, myofibrillar disarray, and enlarged hyperchromatic nuclei (Figure [B]). The extent of fibrosis was only modest, indicating that the hypertrophy had mainly resulted from the increased myocardial mass. Strikingly, immunohistochemical staining for Ki-67 (MIB-1), a widely accepted marker of cell proliferation, showed a marked increase in Ki-67 positive nuclei throughout all regions of the myocardium (Figure [C]). This unexpected finding clearly contrasted with the MIB-1 staining results from age-matched control specimens or cardiomyopathy samples of different etiologies, which showed no
Genotype–phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome
American Journal of Medical Genetics Part A, 2008
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. Phenotypical examination and diagnosis were performed by expert clinical geneticists. The entire PTPN11 and RAF1 coding regions were screened for mutations by DHPLC analysis, followed by sequencing. Patients without PTPN11 mutations (34%) showed a higher frequency of family history of sudden death (P ¼ 0.007), increased left atrial dimensions (P ¼ 0.05), bradyarrhythmias (P ¼ 0.04), episodes of supraventricular tachycardias (P ¼ 0.06), atrial fibrillation (P ¼ 0.009), and nonsustained ventricular tachycardias (P ¼ 0.05) during Holter monitoring. Six patients (25%) had adverse cardiac events during follow-up (including sudden deaths, resuscitated cardiac arrest, septal myectomy, and heart failure). LVH, New York Heart Association Class, left ventricular outflow tract obstruction, and nonsustained ventricular tachycardias were associated to adverse cardiac events. Of note, three patients with mutations in exon 13 showed a severe obstructive cardiomyopathy, with serious cardiac complications during follow-up (heart failure, septal myectomy, and sudden death). In conclusion, patients with LVH associated with LS seem to carry a relatively high risk of adverse (arrhythmic and nonarrhythmic) events. Further genotype-phenotype studies are warranted to fully elucidate the impact of the genotype on the natural history of patients with LS and LVH. ß
LEOPARD syndrome in an infant with severe hypertrophic cardiomyopathy and PTPN11 mutation
Annals of Pediatric Cardiology, 2011
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 genotypephenotype correlation.
FELINE HYPERTROPHIC CARDIOMYOPATHY: CASE REPORT (Atena Editora)
FELINE HYPERTROPHIC CARDIOMYOPATHY: CASE REPORT (Atena Editora), 2023
In domestic felines, cardiomyopathies are identified as structural and functional diseases of the heart muscle, among them, hypertrophic cardiomyopathy is the most prevalent, characterized by thickening of the left ventricle, which can vary from mild to severe, with diastolic dysfunction. Cats as young as three months old, with no sex or breed predilection, may be affected. Mutations in contractile protein genes, generating dysfunctional sarcomeres, have already been described in some pure breeds, therefore it can be considered a primary hereditary disease. Clinical signs are usually associated with dyspnea as a result of pulmonary edema and/or pleural effusion, in addition to the possibility of paresis or quadriplegia of the limbs as a result of arterial thrombi. The diagnosis has the echocardiographic examination as the gold standard. This work aims to describe the clinical signs, diagnosis and therapeutic approach of a young feline, mixed breed, 2 years old, with Hypertrophic Cardiomyopathy, attended at the Animal Health Unit Hospital Victória in the city of Porto Alegre, RS.