Severe nasomaxillary hypoplasia (Binder phenotype) on prenatal US/MRI: an important marker for the prenatal diagnosis of chondrodysplasia punctata

Chondrodysplasia punctata is a skeletal dysplasia caused by a diverse spectrum of etiologies, with outcomes ranging from antenatal demise to a normal life span. Prenatal detection can be challenging.

To review a series of cases of chondrodysplasia punctata associated with nasomaxillary hypoplasia, known as the Binder phenotype, and to highlight prenatal ultrasound and MRI findings, as well as postnatal MRI and radiographic findings.

We retrospectively reviewed ultrasound, MRI and radiographic imaging findings in postnatally confirmed cases of chondrodysplasia punctata from 2001 to 2017. We analyzed prenatal findings and correlated them with maternal history, postnatal imaging, phenotype, genetics and outcome.

We identified eight cases, all with prenatal US and six of eight with prenatal MRI between 18 weeks and 32 weeks of gestational age. Reasons for referral included midface hypoplasia in four cases; family history in one case; intrauterine growth restriction in one case; short long-bones, intrauterine growth restriction and multicystic kidney in one case; and multiple anomalies in one case. In six cases, postnatal radiographs were performed. In four cases, postnatal spine MRI imaging was performed. The diagnosis of chondrodysplasia punctata was suggested in prenatal reports in six of eight fetuses. Seven of eight fetuses had Binder phenotype with severe nasomaxillary hypoplasia. Limb length was mildly symmetrically short in four of eight cases and normal in four of eight fetuses. Two of eight fetuses had epiphyseal stippling identified prenatally by US; this was present postnatally in six neonates on radiographs. Hand and foot abnormalities of brachytelephalangy were not detected on the prenatal US or MRI but were present in six of eigth fetuses on postnatal radiographs or physical exam. Four of eight fetuses had prenatal spine irregularity on US from subtle stippling. Six of eight had spine stippling on postnatal radiographs. One fetus had cervicothoracic kyphosis on prenatal US and MRI, and this was postnatally present in one additional neonate. One case had prenatally suspected C1 spinal stenosis with possible cord compression, and this was confirmed postnatally by MRI. There was a maternal history of systemic lupus erythematosus in two and hyperemesis gravidarum in one. Outcomes included one termination and seven survivors.

Chondrodysplasia punctata can be identified prenatally but findings are often subtle. The diagnosis should be considered when a fetus presents with a hypoplastic midface known as the Binder phenotype. Maternal history of lupus, or other autoimmune diseases or hyperemesis gravidarum can help support the diagnosis.