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International Journal of Dermatology May 2024
PubMed: 38716686
DOI: 10.1111/ijd.17219 -
Orphanet Journal of Rare Diseases May 2008LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym... (Review)
Review
LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4-5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable.
Topics: Adult; Cardiomyopathy, Hypertrophic; Child, Preschool; Face; Female; Humans; LEOPARD Syndrome; Mutation; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Skin
PubMed: 18505544
DOI: 10.1186/1750-1172-3-13 -
QJM : Monthly Journal of the... May 2023
Topics: Humans; LEOPARD Syndrome; Cardiomyopathy, Hypertrophic
PubMed: 36525376
DOI: 10.1093/qjmed/hcac277 -
Kardiologiia Mar 2020LEOPARD syndrome with multiple lentigines (cardiomyopathic lentiginosis) is a rare, genetically predetermined disease with autosomal dominant inheritance. Prevalence of...
LEOPARD syndrome with multiple lentigines (cardiomyopathic lentiginosis) is a rare, genetically predetermined disease with autosomal dominant inheritance. Prevalence of this syndrome is unknown. One of pathognomonic clinical manifestations of this syndrome is the presence of multiple lentiginous pigment spots all over the body. The most common cardiac manifestation (approximately 80%) is myocardial hypertrophy. We presented a rare clinical case of detecting LEOPARD syndrome with multiple lentigines in a 32-year old female patient with major manifestations evident as pronounces morpho-functional alterations, myocardial hypertrophy, and heart rhythm disorders.
Topics: Adult; Female; Heart; Humans; LEOPARD Syndrome
PubMed: 32375626
DOI: 10.18087/cardio.2020.3.n944 -
Dermatology Online Journal Oct 2015LEOPARD syndrome (LS) is an autosomal dominantly inherited or sporadic disorder of variable penetrance and expressivity. The acronym LEOPARD stands for its cardinal...
LEOPARD syndrome (LS) is an autosomal dominantly inherited or sporadic disorder of variable penetrance and expressivity. The acronym LEOPARD stands for its cardinal clinical features including Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, and Deafness. We present herein a patient with LEOPARD syndrome and distinctive features. It was noteworthy that our patient presented with the concern of generalized lentiginosis and subsequent evaluation revealed that the patient had LEOPARD syndrome. In this report we would like to highlight the importance of detailed clinical examination and appropriate imaging in patients with multiple lentigines.
Topics: Biopsy; Diagnosis, Differential; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; LEOPARD Syndrome; Skin; Ventricular Function, Left; Young Adult
PubMed: 26632807
DOI: No ID Found -
Cardiovascular Journal of Africa Jul 2012LEOPARD syndrome (LS) is a rare hereditary disorder, characterised mainly by skin, facial and cardiac abnormalities. We report on the case of a six-year-old Djiboutian...
LEOPARD syndrome (LS) is a rare hereditary disorder, characterised mainly by skin, facial and cardiac abnormalities. We report on the case of a six-year-old Djiboutian with typical features of LS. Multiple cardiovascular problems are described, including pulmonary infundibular, valvular and supra-valvular stenosis. A favourable course was observed after successful cardiac surgery. This is the first reported case of LS from the horn of Africa.
Topics: Cardiac Surgical Procedures; Child; Echocardiography, Doppler; Electrocardiography; Hemodynamics; Humans; LEOPARD Syndrome; Male; Pulmonary Subvalvular Stenosis; Pulmonary Valve Stenosis; Treatment Outcome
PubMed: 22832481
DOI: 10.5830/CVJA-2012-011 -
Best Practice & Research. Clinical... Feb 2011Noonan syndrome is a relatively common, clinically variable developmental disorder. Cardinal features include postnatally reduced growth, distinctive facial dysmorphism,... (Review)
Review
Noonan syndrome is a relatively common, clinically variable developmental disorder. Cardinal features include postnatally reduced growth, distinctive facial dysmorphism, congenital heart defects and hypertrophic cardiomyopathy, variable cognitive deficit and skeletal, ectodermal and hematologic anomalies. Noonan syndrome is transmitted as an autosomal dominant trait, and is genetically heterogeneous. So far, heterozygous mutations in nine genes (PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 and CBL) have been documented to underlie this disorder or clinically related phenotypes. Based on these recent discoveries, the diagnosis can now be confirmed molecularly in approximately 75% of affected individuals. Affected genes encode for proteins participating in the RAS-mitogen-activated protein kinases (MAPK) signal transduction pathway, which is implicated in several developmental processes controlling morphology determination, organogenesis, synaptic plasticity and growth. Here, we provide an overview of clinical aspects of this disorder and closely related conditions, the molecular mechanisms underlying pathogenesis, and major genotype-phenotype correlations.
Topics: Adolescent; Child; Costello Syndrome; Ectodermal Dysplasia; Facies; Failure to Thrive; Heart Defects, Congenital; Humans; Infant; Intracellular Signaling Peptides and Proteins; LEOPARD Syndrome; Loose Anagen Hair Syndrome; Mitogen-Activated Protein Kinases; Neurofibromatosis 1; Noonan Syndrome; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-cbl; Proto-Oncogene Proteins c-raf; SOS1 Protein
PubMed: 21396583
DOI: 10.1016/j.beem.2010.09.002 -
American Journal of Medical Genetics.... Dec 2022RASopathies comprise a group of clinically overlapping developmental disorders caused by genetic variations affecting components or modulators of the RAS-MAPK signaling... (Review)
Review
RASopathies comprise a group of clinically overlapping developmental disorders caused by genetic variations affecting components or modulators of the RAS-MAPK signaling cascade, which lead to dysregulation of signal flow through this pathway. Noonan syndrome and the less frequent, clinically related disorders, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, and Noonan syndrome-like disorder with loose anagen hair are part of the RASopathy spectrum and share a recognizable pattern of multisystem involvement. This review describes the "Noonan syndrome-like" phenotype as a common phenotypic signature of generalized developmental RAS pathway dysregulation. Distinctive features of the different entities are revisited against the background of the understanding of underlying genetic alterations and genotype correlations, which has evolved rapidly during the past 20 years, thereby leading to suggestions regarding the nosology of RASopathies.
Topics: Humans; Noonan Syndrome; Heart Defects, Congenital; Costello Syndrome; Failure to Thrive; Mutation
PubMed: 36428239
DOI: 10.1002/ajmg.c.32015 -
Anales de Pediatria Jul 2020Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other...
Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies». Despite the recent advances in molecular genetics, nearly 20% of patients still lack a genetic cause, and diagnosis is still made mainly on clinical grounds. NS is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, and affects multiple organs and systems. Therefore, it is essential that physicians involved in the care of these patients are familiarised with their manifestations and the management recommendations, including management of growth and development. Data on growth hormone treatment efficacy are sparse, and show a modest response in height gains, similar to that observed in Turner syndrome. The role of RAS/MAPK hyper-activation in the pathophysiology of this group of disorders offers a unique opportunity for the development of targeted approaches.
Topics: Diagnosis, Differential; Genetic Markers; Genotype; Humans; Mitogen-Activated Protein Kinases; Mutation; Noonan Syndrome; Phenotype; Proto-Oncogene Proteins p21(ras)
PubMed: 32493603
DOI: 10.1016/j.anpedi.2020.04.008 -
Singapore Medical Journal Jul 2001The Leopard syndrome is a complex of multisystemic congenital abnormalities characterised by lentiginosis, electrocardiographic conduction abnormalities, ocular... (Review)
Review
The Leopard syndrome is a complex of multisystemic congenital abnormalities characterised by lentiginosis, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth and deafness (sensorineural). Hypertrophic cardiomyopathy, though not included in the mnemonic, is often associated. Although the Leopard syndrome is rare, it is important to recognise it since it can be associated with serious cardiac disease. It is advisable to follow up patients with Leopard syndrome for new onset of cardiac abnormalities and to monitor the progression of existing cardiac disease. We present a case report and review of the literature of this syndrome.
Topics: Abnormalities, Multiple; Adult; Deafness; Genitalia; Growth Disorders; Humans; Hypertelorism; Lentigo; Male; Pulmonary Valve Stenosis; Syndrome
PubMed: 11599630
DOI: No ID Found