Prenatal diagnosis and molecular genetic analysis of short rib-polydactyly syndrome type III (Verma-Naumoff) in a second-trimester fetus with a homozygous splice site mutation in intron 4 in the NEK1 gene
ABSTRACT To demonstrate perinatal imaging findings and to investigate the mutation in the NEK1 gene in a fetus with type III short rib-polydactyly syndrome (SRPS) (Verma-Naumoff).
A 34-year-old woman with no past history of fetal SRPS was referred to the hospital at 21 weeks of gestation because of sonographic diagnosis of short limbs in the fetus. Fetal ultrasound revealed a narrow thorax, short ribs, short limbs with marginal spurs, and postaxial hexadactyly in both the hands and feet. A diagnosis of SRPS III (Verma-Naumoff) was made. Amniocentesis was performed. The karyotype was 46,XY. Molecular genetic analysis of the amniotic fluid cells identified a homozygous splice site mutation in intron 4 (c.331-1 A > G) or IVS4-1 A > G in the NEK1 gene. The parents were heterozygous for the mutation. The pregnancy was subsequently terminated and a malformed fetus was delivered with prominent forehead, a flattened nasal bridge, a narrow and short trunk, a protuberant abdomen, bilateral postaxial polydactyly and syndactyly of the hands and feet, and micromelic limbs. No facial cleft or genital abnormality was noted. The radiograph was consistent with SRPS III.
Polydactyly, micromelia, metaphyseal spurs, widened humeral metaphyses, and shortened ribs can be prominent prenatal ultrasound findings of SRPS III. The present case provides evidence for a correlation of a mutation in the NEK1 gene with SRPS III.
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ABSTRACT: OBJECTIVE: To present the perinatal findings and first-trimester molecular and transabdominal ultrasound diagnosis of a fetus with Ellis-van Creveld (EvC) syndrome. CASE REPORT: A 35-year-old woman was referred for genetic counseling at 13 weeks of gestation because of a family history of skeletal dysplasia. She had experienced one spontaneous abortion, and delivered one male fetus and one female fetus with EvC syndrome. During this pregnancy, a prenatal transabdominal ultrasound at 13(+4) weeks of gestation revealed a nuchal translucency (NT) thickness of 2.0 mm, an endocardial cushion defect, postaxial polydactyly of bilateral hands, and mesomelic dysplasia of the long bones. Amniocentesis was performed at 13(+5) weeks of gestation. Results of a cytogenetic analysis revealed a karyotype of 46,XX and that of a molecular analysis revealed compound heterozygous mutations of c.1195C>T and c.871-2_894del26 in the EVC2 gene. Prenatal ultrasound at 16 weeks of gestation showed a fetus with short limbs, an endocardial cushion defect, and postaxial polydactyly of bilateral hands. The parents decided to terminate the pregnancy, and a 116-g female fetus was delivered with a narrow thorax, shortening limbs, and postaxial polydactyly of the hands. CONCLUSION: Prenatal diagnosis of an endocardial cushion defect with postaxial polydactyly should include a differential diagnosis of EvC syndrome in addition to short rib-polydactyly syndrome, Bardet-Biedl syndrome, orofaciodigital syndrome, Smith-Lemli-Opitz syndrome, and hydrolethalus syndrome.Taiwanese journal of obstetrics & gynecology 12/2012; 51(4):643-648. DOI:10.1016/j.tjog.2012.10.001 · 1.26 Impact Factor