Left Ventricular Noncompaction in Sotos Syndrome
ABSTRACT Sotos syndrome is an autosomal dominant condition characterized by pre- and postnatal overgrowth (tall stature and macrocephaly), a typical facial appearance, advanced bone age, and developmental delay. The syndrome is caused by mutations or deletions of the nuclear receptor binding SET domain protein 1 (NSD1) gene, which encodes a histone methyltransferase implicated in the regulation of chromatin. Left ventricular noncompaction (LVNC), also called left ventricular (LV) hypertrabeculation, is a rare disorder classified as a primary genetic cardiomyopathy by the American Heart Association. This condition is characterized by an altered myocardial wall due to arrest of embryonic compaction of the loose interwoven meshwork that makes up the fetal myocardial primordium. The cardiac manifestations of this cardiomyopathy are variable, ranging from an absence of symptoms to a progressive deterioration in cardiac function, with heart failure, arrhythmias, and systemic thromboemboli. We describe two unrelated patients who had LVNC, as based on echocardiographic findings, and Sotos syndrome, as based on physical features and molecular analysis. To our knowledge, the literature contains no previous reports of concomitant LVNC and Sotos syndrome. In the light of these two cases, we suggest that patients with Sotos syndrome be evaluated for LVNC cardiomyopathy when being screened for heart defects.
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ABSTRACT: Children with generalized overgrowth syndromes are large at birth, or have excessive postnatal growth. Many of these syndromes are associated with an increase in neoplasia. Consideration of the possibility of overgrowth syndrome in a pediatric patient who presents with increased growth parameters, variable malformations and neurodevelopmental phenotype, and distinctive features, is important for medical management, reproductive counseling, and tumor surveillance for some of the disorders. This review describes the clinical features and surveillance recommendations for the common generalized overgrowth syndromes the pediatrician may encounter. It also provides a glimpse into advances of recent years in understanding the molecular mechanisms responsible for the disrupted growth regulation in these disorders. Copyright © 2015 Mosby, Inc. All rights reserved.Current problems in pediatric and adolescent health care 04/2015; 45(4). DOI:10.1016/j.cppeds.2015.02.005 · 1.56 Impact Factor
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ABSTRACT: Noncompaction/hypertrabeculation is increasingly being recognized in children and adults, yet we understand little about the causes of disease. Genes associated with noncompaction/hypertrabeculation have been identified, but how can these assist in clinical management? Genomic technologies have also expanded tremendously, making testing more comprehensive, but they also present new questions given the tremendous diversity of phenotypes and variability of genomes. Here we present genetic evaluation strategies and assess clinical testing options for noncompaction/hypertrabeculation. We assess genes/gene panels offered by clinical laboratories and the potential for high-throughput sequencing to fuel further discovery. We discuss challenges in cardiovascular genetics, such as interpretation of genomic variants, prediction and disease penetrance. © 2013 Wiley Periodicals, Inc.American Journal of Medical Genetics Part C Seminars in Medical Genetics 08/2013; 163(3). DOI:10.1002/ajmg.c.31371 · 3.54 Impact Factor
- International journal of cardiology 02/2013; 168(1). DOI:10.1016/j.ijcard.2013.01.221 · 6.18 Impact Factor