title: Sibling recurrence of total anomalous pulmonary venous drainage.
abstract: Many childhood syndromic disorders are associated with congenital heart defects, but few present specifically with total anomalous pulmonary venous drainage (TAPVD). Here, we report two siblings presenting with TAPVD, tracheo-oesophageal fistula and dysmorphic features in the neonatal period. Careful examination of the mother revealed subtle facial asymmetry and a pre-auricular tag, suggesting a potential variable expression of a dominant disorder. Whole exome sequencing identified a pathogenic heterozygous mutation in EFTUD2, a gene, normally associated with mandibulofacial dystosis Guion-Almedia type (MFDGA), in both siblings and the mother. This is the first report of TAPVD occurring as part of the MFDGA phenotype. It serves to highlight the importance of modern sequencing panels in identifying causative mutations for heterogeneous syndromes such as MFDGA and familial congenital heart defects whilst emphasising the relevance of variable expression when counselling parents.
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Central Manchester Foundation Trust, Oxford Road, Manchester, M13 9WL, United Kingdom. Electronic address: john.mcdermott2@cmft.nhs.uk.
authors.forename: J H
authors.initials: JH
authors.lastname: McDermott
authors.affiliation: Wellcome Trust Sanger Institute, Cambridgeshire, United Kingdom.
authors.forename: D D D
authors.initials: DD
authors.lastname: Study
authors.affiliation: Manchester Centre for Genomic Medicine, St. Mary's Hospital, Central Manchester Foundation Trust, Oxford Road, Manchester, M13 9WL, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Clayton-Smith
mesh_terms: D005260:Female; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006801:Humans; D008297:Male; D011667:Pulmonary Veins / Q000502:physiology*; D035781:Siblings
keywords: Cardiology; Congenital abnormalities; Congenital heart defects; Genetics; Total anomalous pulmonary venous return