American journal of medical genetics. Part A
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Am. J. Med. Genet. A · Feb 2015
Obstructive sleep apnea in young infants with Down syndrome evaluated in a Down syndrome specialty clinic.
Children with Down syndrome (DS) experience congenital and functional medical issues that predispose them to obstructive sleep apnea (OSA). Research utilizing stringent age criteria among samples of infants with DS and OSA is limited. This study examines clinical correlates of OSA among infants with DS. ⋯ Obstructive sleep apnea is relatively common in young infants with DS and often severe. Medical factors including GI conditions, dysphagia and CHD may help to identify infants who are at greater risk and may warrant evaluation. Further studies are needed to assess the impact of OSA in infants with DS.
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Am. J. Med. Genet. A · Oct 2014
CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases.
Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. ⋯ Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present.
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Am. J. Med. Genet. A · Oct 2014
Case ReportsAtypical Aicardi-Goutieres syndrome: is the WRN locus a modifier?
We describe a 28-year-old Turkish man with consanguineous parents who presented with an aged appearance with prematurely gray hair and scleroderma-like skin, spastic paraplegia, and apparent disability. The proband and each of his parents were heterozygous for a mutation in WRN, which could not explain his symptoms. Exome sequencing of the proband's blood DNA showed a homozygous c.626-1G > C mutation in intron 5 of the SAMHD1 gene, which encodes a triphosphohydrolase involved in the regulation of intracellular dNTP pools and which is mutated in Aicardi-Goutieres syndrome. ⋯ We conclude that mutations in SAMHD1 - in addition to causing an early-onset form of encephalopathy in Aicardi-Goutieres syndrome - may present with modest signs of accelerated aging similar to Werner syndrome. The extent to which heterozygosity at the WRN locus may modify the effect of biallelic SAMHD1 mutations is unknown. It is conceivable that synergistic effects of these two mutations might be responsible for the unusual phenotype.
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Am. J. Med. Genet. A · Aug 2014
Fatigue in adults with Marfan syndrome, occurrence and associations to pain and other factors.
This study aims to investigate how fatigue affects adults with verified Marfan syndrome (MFS) in their daily lives, by examining fatigue levels and prevalence of severe fatigue compared to the general Norwegian population and individuals with other comparable chronic conditions. We investigated associations between socio-demographic characteristics, Marfan-related health problems, pain and fatigue. A cross-sectional study was conducted, using a postal questionnaire including the Fatigue Severity Scale (FSS) and questions on socio-demographic characteristics, Marfan-related health problems and pain. ⋯ Chronic pain and employment status show significant associations to fatigue. This implies that fatigue is important to address when meeting MFS patients in clinical practice. There is need for more research on fatigue in Marfan syndrome.
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Am. J. Med. Genet. A · Aug 2014
The spectrum of ZEB2 mutations causing the Mowat-Wilson syndrome in Japanese populations.
Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by moderate or severe intellectual disability, a characteristic facial appearance, microcephaly, epilepsy, agenesis or hypoplasia of the corpus callosum, congenital heart defects, Hirschsprung disease, and urogenital/renal anomalies. It is caused by de novo heterozygous loss of function mutations including nonsense mutations, frameshift mutations, and deletions in ZEB2 at 2q22. ZEB2 encodes the zinc finger E-box binding homeobox 2 protein consisting of 1,214 amino acids. ⋯ A transfection study demonstrated that the cellular level of the longest form of the mutant ZEB2 protein harboring the p. D1204Rfs*29 mutation was remarkably low. The results showed that the 3'-end frameshift mutation of ZEB2 causes MWS due to ZEB2 instability.