Earliest ultrasound findings and description of splicing mutations in Meckel-Gruber syndrome

To describe early ultrasound findings in Meckel-Gruber syndrome (MKS) in first and second trimester of three families, detailed ultrasound findings have been documented in addition to pathoanatomical findings and results of DNA studies. A splice site mutation in the MKS4 gene could be detected. Clinical management accounting risk assessment for future pregnancies is discussed and early ultrasound markers in MKS are described. All cases were examined in a tertiary center for prenatal diagnosis by ultrasound. Necroscopy confirmed the clinical diagnosis. Fetal DNA analysis was accomplished in a reference center for MKS. In addition, ultrasound findings in early pregnancy of two further cases are described. Three couples presented with pregnancies complicated by MKS. The earliest diagnosis was suspected in 11 + 6 weeks of gestation and was confirmed in 13 + 0 weeks by ultrasound revealing a large occipital encephalocele and polycystic kidneys. Another case with recurrent MKS in two consecutive pregnancies was diagnosed in 20 weeks and 14 weeks of gestation, respectively. Here a close molecular genetic follow-up was performed leading to the detection of two mutations in the MKS4 gene in both fetuses. The third case was diagnosed in 15 weeks of gestation. Ultrasound findings in all pregnancies were doubtless and autopsies confirmed the diagnosis. Detection of MKS is already possible in the first trimester. Knowledge of the underlying genetic defect helps counseling the couples with recurrence of MKS and chorionic villi sampling in the first trimester of pregnancy can be offered.