Left Ventricular Noncompaction in Sotos Syndrome
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.
Available from: Eva Klopocki
- "LVHT has been reported in association with epilepsy, facial dysmorphism or minor anomalies
[1,4,12-18]. Several chromosomal aberrations have been identified in LVHT associated with heart defects
[1,4,8,10,12,15-17]. We present a pediatric patient with LVHT and other right and left heart defects, epilepsy and minor facial anomalies in whom microarray-based comparative genomic hybridization (array CGH) detected new copy number variants (CNVs). "
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Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology which has been described in children as well as in adults with and without chromosomal aberrations. LVHT has been reported in association with various cardiac and extracardiac abnormalities like epilepsy and facial dysmorphism.
A unique combination of LVHT, atrial septal defect, pulmonary valve stenosis, aortic stenosis, epilepsy and minor facial anomalies is presented in a 5.5 years old girl. Microarray-based genomic hybridization (array-CGH) detected six previously not described copy number variants (CNVs) inherited from a clinically unaffected father and minimally affected mother, thus, most likely, not clinically significant but rare benign variants.
Despite this complex phenotype de novo microdeletions or microduplications were not detected by array CGH. Further investigations, such as whole exome sequencing, could reveal point mutations and small indels as the possible cause.
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ABSTRACT: Cobalamin C disease (cblC), a form of combined methylmalonic acidemia and hyperhomocysteinemia caused by mutations in the MMACHC gene, may be the most common inborn error of intracellular cobalamin metabolism. The clinical manifestations of cblC disease are diverse and range from intrauterine growth retardation to adult onset neurological disease. The occurrence of structural heart defects appears to be increased in cblC patients and may be related to the function of the MMACHC enzyme during cardiac embryogenesis, a concept supported by the observation that Mmachc is expressed in the bulbis cordis of the developing mouse heart. Here we report an infant who presented with hydrops fetalis, ventricular dysfunction, and echocardiographic evidence of LVNC, a rare congenital cardiomyopathy. Metabolic evaluations, complementation studies, and mutation analysis confirmed the diagnosis of cblC disease. These findings highlight an intrauterine cardiac phenotype that can be displayed in cblC disease in association with nonimmune hydrops.
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