We report a case of two consecutive pregnancies in the same couple presenting with very low pregnancy-associated plasma protein A (PAPP-A), with both pregnancies affected by multiple anomalies of a similar phenotype identified during mid-trimester ultrasound, and eventual diagnosis of Peters-plus syndrome. This case is important in expanding the differential for very low PAPP-A. It also demonstrates the diagnostic value of whole-exome sequencing (WES) after prenatal diagnosis of recurrent fetal ultrasonographic findings. The importance and complexity of providing patient education to enable informed consent for next generation sequencing technologies is discussed.

 We report a case of two consecutive pregnancies in the same couple presenting with very low pregnancy-associated plasma protein A (PAPP-A), with both pregnancies affected by multiple anomalies of a similar phenotype identified during mid-trimester ultrasound, and eventual diagnosis of Peters-plus syndrome. This case is important in expanding the differential for very low PAPP-A. It also demonstrates the diagnostic value of whole-exome sequencing (WES) after prenatal diagnosis of recurrent fetal ultrasonographic findings. The importance and complexity of providing patient education to enable informed consent for next generation sequencing technologies is discussed.

BACKGROUND: Peters Plus syndrome (MIM 261540) is a rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor abnormalities. Mutations in the B3GALTL gene encoding the β-1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome.
METHODS: We report here a female patient with severe manifestations of Peters Plus syndrome including facial dysmorphism and bilateral corneal opacity associated with left renal pyelo-calicial dilatation and sexual ambiguity. Total sequencing of the B3GALTL gene revealed no mutation in the patient.
CONCLUSIONS: To our knowledge, sexual ambiguity has not previously been reported in Peters Plus syndrome so far, and renal malformation is also apparently rare in the syndrome.