In children, DCM is a diverse disorder with outcomes that depend largely on cause, age, and heart failure status at presentation. Race, sex, and age affect the incidence of disease. Most children do not have a known cause of DCM, which limits the potential for disease-specific therapies.

In germ cells and the early embryo, the mammalian genome undergoes widespread epigenetic reprogramming. Animal studies suggest that this process is vulnerable to external factors. We report two children who were conceived by intracytoplasmic sperm injection (ICSI) and who developed Angelman syndrome. Molecular studies, including DNA methylation and microsatellite and quantitative Southern blot analysis, revealed a sporadic imprinting defect in both patients. We discuss the possibility that ICSI may interfere with the establishment of the maternal imprint in the oocyte or pre-embryo.

Background-Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. Methods and Results-The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. We identified the various causes of HCM in childhood and determined the relationship between outcomes, cause, and age at presentation. Of 855 patients Ͻ18 years of age with HCM, 8.7% (nϭ74) had inborn errors of metabolism, 9.0% (nϭ77) had malformation syndromes, 7.5% (nϭ64) had neuromuscular disorders, and 74.2% (nϭ634) had idiopathic HCM. Children with HCM associated with inborn errors of metabolism and malformation syndromes have significantly worse survival than the other 2 groups. Patients with idiopathic HCM diagnosed before 1 year of age (nϭ227) had worse survival from the time of diagnosis than those diagnosed after 1 year of age (nϭ407). Patients with idiopathic HCM who survived to at least 1 year of age, however, had an annual mortality rate of 1% that was similar regardless of whether they were diagnosed before or after 1 year of age. Conclusions-In children, HCM is a diverse disorder with outcomes that depend largely on cause and age. Patients presenting before 1 year of age have the broadest spectrum of causes and the poorest outcome. In those children with idiopathic HCM who survive beyond age 1, however, survival is independent of age at diagnosis, with an annual mortality rate (1%) that is much lower than previously reported in children and is not different from has been found in population-based studies in adults.

The estimated incidence of pediatric cardiomyopathy in two large regions of the United States is 1.13 cases per 100,000 children. Most cases are identified at an early age, and the incidence varies according to sex, region, and racial or ethnic origin.

This trial demonstrates the long-term clinical benefit and safety of laronidase in attenuated patients with mucopolysaccharidosis I and highlights the magnitude and chronology of treatment effects. Prompt diagnosis and early treatment will maximize treatment outcomes.

Background Segmental duplications at breakpoints (BP4–BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or EEG abnormalities. Patients DNA samples from 1,445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children’s Hospital Boston and DNA samples from 1,441 individuals with Autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. Results We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4–BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4–BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, ADHD, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4–BP5 covers ~1.5Mb (chr15:28.719–30.298Mb) and includes 6 reference genes and 1 miRNA gene, while the smaller duplications cover ~500 kb (chr15:28.902–29.404 Mb) and contain 3 reference genes and one miRNA gene. The BP4–BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. Conclusions The phenotype of chromosome 15q13.2q13.3 BP4–BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying etiology of this syndrome.

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