Arthrogryposis as neonatal presentation of Loeys-Dietz syndrome due to a novel TGFBR2 mutation.
Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized mainly by cardiovascular, craniofacial and skeletal features. We report on a patient with LDS, whose prenatal examination was compatible with the diagnosis of arthrogryposis multiplex congenita. Neonatal assessment showed craniofacial and cardiovascular findings suggestive of LDS whose diagnosis was confirmed by the detection of a novel mutation (HGVN: NM_003242.5 (TGFBR2): c.1381T > C (p.(Cys461Arg))) in the TGFBR2 gene. Few prenatal and neonatal cases of LDS have been reported in the literature. We reviewed all cases reported to date with perinatal onset to delineate the clinical manifestations that allow us to prompt diagnosis of this syndrome at an early stage to prevent fatal cardiovascular complications. Furthermore we discuss the multidisciplinary follow up required in these patients.
Department of Clinical and Molecular Genetics and Rare Disease Unit, University Hospital Vall d'Hebron, CIBERER, Barcelona, Spain.
Irene
I
Valenzuela
Department of Clinical and Molecular Genetics and Rare Disease Unit, University Hospital Vall d'Hebron, CIBERER, Barcelona, Spain.
Paula
P
Fernández-Alvarez
Neuropediatrics Service, University Hospital Vall d'Hebron, Barcelona, Spain.
Francina
F
Munell
Pediatric Radiology, University Hospital Vall d'Hebron, Barcelona, Spain.
Angel
A
Sanchez-Montanez
Pediatric Cardiology, University Hospital Vall d'Hebron, Barcelona, Spain.
Gemma
G
Giralt
Department of Clinical and Molecular Genetics and Rare Disease Unit, University Hospital Vall d'Hebron, CIBERER, Barcelona, Spain.
Teresa
T
Vendrell
Department of Clinical and Molecular Genetics and Rare Disease Unit, University Hospital Vall d'Hebron, CIBERER, Barcelona, Spain. Electronic address: etizzano@vhebron.net.
Eduardo F
EF
Tizzano
D001176:Arthrogryposis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D055947:Loeys-Dietz Syndrome / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
Aneurysm; Aortic root dilatation; Arterial tortuosity; Arthrogryposis multiplex congenita; Cleft palate; Connective tissue disorder; Loeys Dietz syndrome; TGFBR2 gene