American journal of medical genetics. Part A
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Am. J. Med. Genet. A · Jul 2013
Case ReportsSevere obstructive sleep apnea in Loeys-Dietz syndrome successfully treated using continuous positive airway pressure.
Loeys-Dietz syndrome is a recently recognized connective tissue disorder characterized by severe craniofacial and skeletal abnormalities as well as arterial tortuosity with aggressive aneurysm formation. Marfan syndrome, a classic connective tissue disorder, is known to be associated with a risk of obstructive sleep apnea, but sleep-related breathing disorders have not been previously documented in Loeys-Dietz syndrome. The propositus had the prototypic features of Loeys-Dietz syndrome with a de novo mutation in TGFBR2. ⋯ Despite the severity of obstructive sleep apnea in the propositus, the administration of continuous positive airway pressure was highly effective in alleviating his symptoms. In summary, severe obstructive sleep apnea was successfully treated using continuous positive airway pressure in a patient with Loeys-Dietz syndrome. Careful evaluation and aggressive intervention for the alleviation of obstructive sleep apnea is warranted in Loeys-Dietz syndrome.
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Am. J. Med. Genet. A · Jul 2013
Case ReportsDeletions of 16p11.2 and 19p13.2 in a family with intellectual disability and generalized epilepsy.
Rare copy number variants (CNVs) have been established as an important cause of various neurodevelopmental disorders, including intellectual disability (ID) and epilepsy. In some cases, a second CNV may contribute to a more severe clinical presentation. Here we present two siblings and their mother who have mild ID, short stature, obesity and seizures. ⋯ The second is a 0.9 Mb deletion of 19p13.2, which results in the deletion of a cluster of zinc finger genes. We suggest that, while the 16p11.2 deletion is likely the primary cause of the obesity and ID in this family, the 19p13.2 deletion may act as a modifier of the epilepsy phenotype, which is not a core feature of the 16p11.2 deletion syndrome. We investigate the potential role of ZNF44, a gene within the deleted region, in a cohort of patients with generalized epilepsy.
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Am. J. Med. Genet. A · Jun 2013
Review Case ReportsExpanding the phenotype of cardiovascular malformations in Adams-Oliver syndrome.
We describe a newborn with a phenotype consistent with Adams-Oliver syndrome and truncus arteriosus. Although cardiovascular malformations associated with this syndrome have been previously published in the literature, this is the first description of truncus arteriosus in a patient with Adams-Oliver syndrome. We review other reports of Adams-Oliver syndrome previously described with cardiovascular malformations, consider possible genetic and embryologic mechanisms, and emphasize the need for cardiology consultation when a diagnosis of Adams-Oliver syndrome is suspected in the differential diagnosis.
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Am. J. Med. Genet. A · Apr 2013
Case ReportsInversion upstream of FOXF1 in a case of lethal alveolar capillary dysplasia with misalignment of pulmonary veins.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a congenital malformation that leads to severe pulmonary hypertension and respiratory failure. It has been associated with deletion of, or mutation in, FOXF1 on 16q24.1, a gene encoding a forkhead transcription factor expressed in the mesenchyme of the developing lung. Here we report on the identification of a pericentric inversion on chromosome 16 (p11.2q24.1) in a case of lethal ACDMPV with atrioventricular septal defect and duodenal atresia. ⋯ Another putative insulator occurs just downstream of FOXF1. Our results further strengthen the association between FOXF1 and a spectrum of malformations that include ACDMPV, atrioventricular septal defects, and gastrointestinal atresia. Furthermore, the presented analysis aids in defining the critical genomic region for this syndrome.
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Am. J. Med. Genet. A · Feb 2013
Multicenter StudyEpilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.
Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. ⋯ Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.