Retrospective diagnosis and subsequent prenatal diagnosis of Nijmegen breakage syndrome

We report on the retrospective diagnosis of Nijmegen breakage syndrome (NBS) confirmed by molecular genetic analysis and consecutive prenatal diagnosis in the same family.

Thirteen years after the death of their daughter due to fatal recurrent infections, a couple presented in our genetic counselling unit asking for the recurrence risk of their daughter's disease. Retrospective analysis of the medical record suggested that the girl might have suffered from NBS. Therefore, molecular genetic analysis for NBS was performed in the parents.

After the diagnosis, NBS could be indirectly proven by molecular genetic heterozygosity testing of the parents, and a reliable prenatal diagnosis for a new pregnancy could be offered. In a following pregnancy, a massive hydrocephalus was diagnosed by ultrasound investigation. Amniocentesis was performed, and molecular analysis of the fetal DNA revealed homozygosity for the NBS1 mutation 657del5.

The analysis of this family allows a further delineation of the prenatal NBS phenotype including hydrocephalus and dystopic kidneys that are helpful parameters to recognise NBS prenatally, also by ultrasound investigations in pregnancy. Additionally, we conclude that hydrocephalus might be more common in NBS patients than previously suggested.