title: Fetal akinesia deformation sequence due to a congenital disorder of glycosylation.
abstract: Congenital disorders of Glycosylation (CDG) are increasingly emerging as a major underlying etiology for patients with complex neurogenetic malformations and dysmorphic features. We describe a newborn female with arthrogryposis multiplex due to fetal akinesia secondary to CDG-DPAGT1. Pregnancy was complicated by reduced fetal movements. At birth, the patient was evaluated for intrauterine growth restriction, bilateral cataracts, and multiple joint contractures. She had markedly reduced spontaneous movements, hypotonia, weak cry, and poor suck. She had ventilator-dependent central respiratory depression. Brain MRI showed delayed myelination and an incomplete cerebellar vermis. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation. Sequencing revealed a homozygous missense mutation in dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1), exon 3, p.Leu118Val, consistent with DPAGT1-CDG. There have been seventeen previously reported cases of DPAGT1-CDG, including two similar cases with multiple contractures. This case highlights the importance of considering congenital disorders of glycosylation in the differential diagnosis for arthrogryposis.
authors.affiliation: Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Section of Biochemical Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ganetzky
authors.affiliation: Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Section of Biochemical Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.affiliation: The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Andrew
authors.initials: A
authors.lastname: Edmondson
authors.affiliation: Section of Biochemical Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Colleen Clarke
authors.initials: CC
authors.lastname: Muraresku
authors.affiliation: Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.affiliation: Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Matthew
authors.initials: M
authors.lastname: Deardorff
authors.affiliation: Genetics Program, Children's Regional Hospital, Cooper University Health Care.
authors.forename: Jaya
authors.initials: J
authors.lastname: Ganesh
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000595:Amino Acid Sequence; D001176:Arthrogryposis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002972:Cleft Palate / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018981:Congenital Disorders of Glycosylation / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003286:Contracture / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006801:Humans; D006849:Hydrocephalus / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D017351:N-Acetylglucosaminyltransferases; C047835:dolichyl-phosphate alpha-N-acetylglucosaminyltransferase
keywords: Congenital disorder of glycosylation type IJ; arthrogryposis; dolichyl-phosphate alpha-N-acetylglucosaminyltransferase