Prenatal Diagnosis of Congenital Hypophosphatasia : A Report of 2 Consecutive Pregnancies

Abstract

Hypophosphatasia, an inherited autosomal recessive, is characterized by the demineralization of bones associated with deficiency of alkaline phosphatase. The incidence is 1 in 100,000 births. Accurate prenatal diagnosis of this lethal skeletal dysplasia is now possible, and the option of pregnancy termination can be offered. A 27 year-old primigravida, 25 weeks of gestation, presented with large-for-date uterine size. The obstetric ultrasound showed polyhydramnios, poorly ossified and globular thin cranium. The soft skull could be compressed transabdominally with ultrasound tranducer. All of bony structures were delicate, and diffusely demineralized. However, vertebral bodies, both femurs, and humerus had some degree of ossification, shortened, and bowed but had no apparent fracture. The sonographic findings were most likely related to hypophosphatasia. Two years later, the same patient presented to the antenatal clinic with the second pregnancy at 7 weeks' gestation. The screening ultrasound at 15 weeks revealed normal with exception for rather short femurs. The follow up ultrasound at 19 weeks showed a single fetus with micromelia without fractures, thin and poorly ossified cranium, ribs, vertebrae, and all of long bones. Only three abdominal vertebral bodies were somewhat ossified. Based on the sonographic findings and previous history of first pregnancy, the diagnosis of recurrent congenital hypophosphatasia was made. Both pregnancies were electively terminated. Postnatal radiographs, autopsies and serum alkaline phosphatase levels confirmed the prenatal diagnosis.