Use of Next-generation Sequencing for Prenatal Diagnosis of Hypophosphatasia

We report on a patient who had recurrent skeletal dysplasia in three of four of her pregnancies which all resulted in termination of pregnancies. The ultrasound and / or histological findings of her first and fourth pregnancy were suggestive of osteogenesis imperfecta while those in her second pregnancy were more suggestive of achondrogenesis. The exact diagnosis could not be made clinically at that time. With the emergence of next-generation sequencing (NGS), the stored placental tissue from her second pregnancy was retrieved for testing 4 years after the pregnancy was terminated. NGS detected two heterozygous pathogenic variants in the ALPL gene which were associated with autosomal recessive hypophosphatasia. This case demonstrated the usefulness of NGS in making an exact diagnosis on the type of skeletal dysplasia which was important in counselling the patients on the risk of recurrence, and offering prenatal diagnosis in their future pregnancies.