Multidisciplinary approach to reach a foetal diagnosis of Walker-Warburg syndrome: From autopsy to genetics and back

The diagnosis of central nervous system anomalies is a challenge for pathologists, especially in the context of stillbirth. A multidisciplinary approach including gestational data, ultrasound, and genetic tests not only increases diagnostic efficacy, but also enhances the quality of care provided to families. We report the case of a legal termination of pregnancy due to encephalic malformation in a couple with a previous history of multiple miscarriages. The initial foetal autopsy guided the genetic tests, leading to the identification of a pathogenic variant responsible for Walker-Warburg syndrome – an infrequent and relatively unknown syndromic complex. By using a reverse phenotyping strategy, it was possible not only to confirm the diagnosis suggested by the genetic tests in the foetus, but also to identify the same genetic alteration in a previous miscarriage. This provided an unidentified diagnosis and enabled the provision of genetic counselling to the couple.