title: Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation.
abstract: Autosomal recessive cutis laxa is a genetically heterogeneous condition. Its molecular basis is largely unknown. Recently, a combined disorder of N- and O-linked glycosylation was described in children with congenital cutis laxa in association with severe central nervous system involvement, brain migration defects, seizures and hearing loss. We report on seven additional patients with similar clinical features in combination with congenital disorder of glycosylation type IIx. On the basis of phenotype in 10 patients, we define an autosomal recessive cutis laxa syndrome. The patients have a complex phenotype of neonatal cutis laxa, transient feeding intolerance, late closure of the fontanel, characteristic facial features including down-slanting palpebral fissures, short nose and small mouth, and developmental delay. There is a variable degree of the central nervous system involvement and variable systemic presentation. The biochemical analysis using transferrin isoelectric focusing gives false negative results in some of the youngest patients. Analysis of the apolipoprotein C-III isoelectric focusing, however, is diagnostic in all cases.
authors.affiliation: Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. E.Morava@cukz.umcn.nl
authors.forename: E
authors.initials: E
authors.lastname: Morava
authors.forename: D J
authors.initials: DJ
authors.lastname: Lefeber
authors.forename: Z
authors.initials: Z
authors.lastname: Urban
authors.forename: L
authors.initials: L
authors.lastname: de Meirleir
authors.forename: P
authors.initials: P
authors.lastname: Meinecke
authors.forename: G
authors.initials: G
authors.lastname: Gillessen Kaesbach
authors.forename: J
authors.initials: J
authors.lastname: Sykut-Cegielska
authors.forename: M
authors.initials: M
authors.lastname: Adamowicz
authors.forename: I
authors.initials: I
authors.lastname: Salafsky
authors.forename: J
authors.initials: J
authors.lastname: Ranells
authors.forename: E
authors.initials: E
authors.lastname: Lemyre
authors.forename: J
authors.initials: J
authors.lastname: van Reeuwijk
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003483:Cutis Laxa / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006031:Glycosylation; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome