| Popis: |
Background: Phelan-McDermid syndrome (PMS), or 22q13.3 deletion syndrome, is a neurodevelopmental disorder with an estimated prevalence of 1 in 10,000 to 20,000 newborns. It usually occurs de novo, but an unexpectedly high recurrence risk is observed in some families. Our aim is to provide an overview of the underlying causes of recurrence in families with PMS and to summarize the available detection methods used to assess increased recurrence risk. Methods: We report clinical and (cyto)genetic data for five families with a high recurrence risk for PMS and provide an overview of Dutch families and cases from literature. We also outline a comprehensive work-up of additional cytogenetic testing to follow initial diagnosis in a proband. Results: Using fluorescent in situ hybridization (FISH), we confirmed a paternal translocation in two and a maternal mosaicism in three of our reported families. Of 34 cytogenetically investigated Dutch families, 16 to 20% have a high recurrence risk based on a parental chromosomal rearrangement. We found 18 additional families in the literature. Conclusions: Parental translocations and mosaicisms are not rare events in families with PMS, making follow-up FISH testing necessary. However, existing methods may still miss low-grade parental mosaicisms, and prenatal testing should always be offered. |
