title: Prenatal findings in carpenter syndrome and a novel mutation in RAB23.
abstract: Carpenter syndrome is caused by mutations of the RAB23 gene. To date, 12 distinct mutations have been identified among 34 patients from 26 unrelated families. We report on the prenatal findings in a fetus with Carpenter syndrome with a novel RAB23 mutation. Cystic hygroma, bowed femora, abnormal skull shape and a complex heart defect were seen on ultrasound scan, and Carpenter syndrome was diagnosed at birth. Craniosynostosis and preaxial hexadactyly of the feet were retrospectively detectable on the fetal CT scan. Sequencing of RAB23 identified a homozygous mutation leading to skipping of exon 6 and premature termination codon (c.481G>C; p.Val161Leufs*16). This observation illustrates the difficulty of prenatal ultrasound diagnosis of Carpenter syndrome. To our knowledge, this diagnosis was suggested on ultrasound scan in only one prior patient, although in five other patients abnormal skull shape and variable findings, mainly limb anomalies including bowed femora in one case, were described during the pregnancy. Heart defect and bowed femora are rare postnatal findings. The diagnosis of Carpenter syndrome should therefore be considered on prenatal imaging in cases of bowed femora and/or cardiac defect associated with abnormal skull shape.
authors.affiliation: Service de Génétique, Hôpital Bretonneau, Centre Hospitalier Universitaire, Tours, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Haye
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.forename: Catherine
authors.initials: C
authors.lastname: Sembely-Taveau
authors.forename: Georges
authors.initials: G
authors.lastname: Haddad
authors.forename: Christelle
authors.initials: C
authors.lastname: Denis
authors.forename: Nathalie
authors.initials: N
authors.lastname: Soulé
authors.forename: Annie-Laure
authors.initials: AL
authors.lastname: Suc
authors.forename: Antoine
authors.initials: A
authors.lastname: Listrat
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
mesh_terms: D000168:Acrocephalosyndactylia / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D017398:Alternative Splicing; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D056973:Four-Dimensional Computed Tomography; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012886:Skull / Q000002:abnormalities; D016216:Ultrasonography, Prenatal; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: C486614:RAB23 protein, human; D020691:rab GTP-Binding Proteins
keywords: RAB23 gene; acrocephalopolysyndactyly type II; bowed femora; carpenter syndrome; heart defect; prenatal diagnosis