3-D ultrasound imaging of a prenatally diagnosed Beckwith–Wiedemann syndrome

Abstract

Imprinting disorders resulting in different syndromes such as Beckwith–Wiedemann syndrome (BWS), Silver–Russel syndrome or Angelman syndrome should be of great interest in prenatal diagnosis with respect to counseling the patients. BWS is an overgrowth syndrome associated with congenital malformations such as macroglossia, abdominal wall defects and increased incidence of embryonic tumors. The disorder has been linked to the chromosomal region 11p15.5, a region that harbours two clusters of imprinted genes (IC1 and IC2). With the exception of CDKN1C gene mutations, all alterations result from defects of the epigenetic regulation of 11p15 gene expression [1]. We present a fetus where the prenatally suspected diagnosis of BWS was confirmed postnatally by karyotyping. The pregnancy of our patient was complicated by unclear maternal anaemia, polyhydramnios and gestational diabetes. Prenatal ultrasound at 28 weeks suggested the fetus to suffer from BWS. Postnatal molecular analysis showed hypomethylation of imprinting centre 2 in the chromosomal region 11p15 thereby confirming the prenatal diagnosis. Ultrasound findings with a 3-D ultrasound picture showing the characteristic features of the fetus at 28 weeks of gestation are presented. We report on a 30-year-old gravida VII para II. The proposita is mentally retarded. The family history is suspicious for a major problem with mental retardation through at least three generations. The patient has an 11-year-old daughter with mild mental retardation and an 11-month-old son who is reported to be healthy so far. All pregnancies result from different fathers, the recent father is slightly mentally retarded as well. Four abortions are documented. At 28 weeks of gestation, the patient was sent to our hospital with an unclear anaemia Ultrasound findings of the fetus revealed a hydropic placenta, large abdominal circumference [95th percentile, hepatomegaly, polyhydramnios (Fig. 1a, b) and normal ultrasound Doppler parameters without signs of anaemia in the mid cerebral artery. A 3-D image gave a typical aspect with macroglossia, thus a BWS was suspected (Fig. 2). Pregnancy was complicated by unclear maternal anemia and polyhydramnios (Hb 7, 4 g/dl). Gestational diabetes (BMI [30) and a Faktor V-Leiden mutation (heterozygous) were diagnosed. The persistent anaemia was treated with transfusions, diabetes needed treatment with insulin. At 34 ? 0 weeks of pregnancy early onset of labour could not be stopped resulting in a caesarean section. The birth weight of the male newborn was 4,200 g (1.2 kg above the 97 percentile), birth length was 55 cm (4 cm above the 97 percentile) and head circumference was 35 cm (97 percentile) revealing severe macrosomia. Apgar was 6/7/8 and umbilical cord pH was 7.26. Due to the family history a karyotyping of the patient was initiated already at 28 weeks with the idea that chromosome 11 might be abnormal. As the critical region for BWS is located on chromosome 11 and the patient revealed an unclear anaemia, a possible reason was suspected to be a mutation in this region. Chromosome banding analysis revealed the mother to carry regular female (46, XX) karyotype, postnatal clinical findings in the male newborn showed typical dysmorphic characteristics for BWS. Cytogenetic analysis on blood lymphocytes revealed a C. Eckmann-Scholz (&) W. Jonat Universitatsklinikum Schleswig-Holstein, Frauenklinik Campus Kiel, Arnold-Heller-Str.24, Haus 3, 24105 Kiel, Germany e-mail: christel.eckmann@uksh.de