Prenatal Ultrasound Diagnosis in 51 Cases of Holoprosencephaly: Craniofacial Anatomy, Associated Malformations, and Genetics

Objective To analyze the prenatal ultrasound findings of the craniofacial and extracephalic anatomy, the postnatal pathological findings, and the genetic anomalies in 51 cases of holoprosencephaly (HPE). Materials and Methods Between 1990 and 2005, a collective of 51 fetuses with tentative ultrasound diagnosis of HPE was recruited at two tertiary referral centers for prenatal ultrasound diagnostics via the Pia Fetal Database (GE Medical Systems, Webling, Germany). Cephalic as well as extracephalic anomalies were investigated, and all cases were subdivided into the subgroups lobar, alobar, and semilobar HPE. In addition to the ultrasound investigation, 45 fetuses were analyzed for genetic anomalies and 21 fetuses underwent an autopsy. Results The average age at diagnosis was 21.9 weeks of gestation. There was a greater number of female fetuses, with an overall ratio of 2.67:1. In 61% of all cases, there was a reduction of growth in comparison with healthy fetuses of the same age. Within the second trimenon, the cephalic anomalies became evident when investigating the diameter of the fetal head (second trimenon: 71% below the fifth percentile; third trimenon: 92% below the fifth percentile). In 82% of the cases, extracephalic anomalies were diagnosed additionally. In 63%, the diagnosis of holoprosencephaly led to a termination of pregnancy. Ten percent of the fetuses were born alive. In 81% of the cases, the diagnosis of HPE was confirmed postnatally. The remaining 19% showed other severe cephalic and extracephalic anomalies. Chromosomal anomalies were detected in 79% of the fetuses, most frequently trisomy 13 (59%). Discussion Because of recent advances in the development and improvement of high-resolution ultrasound, early diagnosis of congenital anomalies such as HPE is now possible. In this study, which represents the largest collection of prenatally diagnosed HPE reported in the literature to date, the average age at diagnosis was earlier than in other studies. The ultrasound devices of today provide excellent images of the fetus that allow an exact diagnosis of craniomaxillofacial anomalies as well as extracephalic anomalies. Apart from a very few cases, the diagnosis of HPE is incompatible with life.