Prenatal manifestation and management of a mother and child affected by spondyloperipheral dysplasia with a C-propeptide mutation in COL2A1: case report

Abstract

It is not unusual for patients with "rare" conditions, such as skeletal dysplasias, to remain undiagnosed until adulthood. In such cases, a pregnancy may unexpectedly reveal hidden problems and special needs. A 28 year old primigravida was referred to us at 17 weeks for counselling with an undiagnosed skeletal dysplasia with specific skeletal anomalies suggesting the collagen 2 disorder, spondyloperipheral dysplasia (SPD; MIM 156550).She was counselled about the probability of dominant inheritance and was offered a prenatal diagnosis by sonography. US examination at 17, 18 and 20 weeks revealed fetal macrocephaly, a narrow thorax, and shortening and bowing of long bones. The parents elected to continue the pregnancy. At birth the baby showed severe respiratory distress for four weeks which then resolved. Mutation analysis of both mother and child revealed a hitherto undescribed heterozygous nonsense mutation in the C-propeptide coding region of COL2A1 confirming the diagnosis of SPD while reinforcing the genotype-phenotype correlations between C-propeptide COL2A1 mutations and the SPD-Torrance spectrum. This case demonstrates the importance of a correct diagnosis even in adulthood, enabling individuals affected by rare conditions to be made aware about recurrence and pregnancy-associated risks, and potential complications in the newborn.

Figure 1

Radiographs of hands. Note mild shortening of the fifth metacarpal of the hands.

Figure 2

Radiographs of feet. Note the 2^nd and 4^th metatarsal bones and the great toe.

Figure 3

Radiographs of patient 1. A. 4 years. B. 28 years. Note short iliac bones, flattened femoral heads, short and broad femoral neck. Short femoral and tibial diaphysys, methaphyseal widening and broad femoral ends.

Figure 4

Radiographs of patient 1. A. 6 years. B. 28 years. Note generalized platyspondyly, thoracolumbar scoliosis.

Figure 5

Fetal auxological measurements showing the shortening of the femur beginning with the 15th the week of gestation.

Figure 6

Patient 2, 2 years. Note flat mid-face, depressed nasal bridge.

Figure 7

Radiological features of patient 2. There is retarded ossification of the skeleton with absence of the ossification centres of pubic bones and distal femoral and proximal tibial epiphyses. Mild platyspondyly with ovoid-pear-shaped vertebral bodies. The tubular bones are short and broad with splayed ends and cupped metaphyses and mild bowing of the tibiae.