The term hypotelorism was used as early as 1960 to indicate a decrease in interorbital distance (Judisch et al., 1984). Ocular hypotelorism is defined as a decreased distance between the eyes or pupils, whereas orbital hypotelorism is defined as a shortened distance between the medial aspects of the orbital walls, with reduced inner and outer canthal distances (Converse et al., 1975; Judisch et al., 1984). The major concern regarding the finding of fetal hypotelorism is its association with midline craniofacial defects and major cerebral anomalies.

Orbital hypotelorism results from developmental abnormalities of the telencephalon, which is a derivative of the forebrain. It is strongly associated with holoprosencephaly (see Chapter 14) (Converse et al., 1975; Achiron et al., 1995). Frequently, hypotelorism is more obvious radiographically or sonographically than clinically. In one study, the normal range of interorbital distances was documented in anteroposterior facial radiographs obtained in 250 normal children. The mean values ranged from 15 mm in infancy to 23 mm at 12 years of age. The interorbital distance was found to be narrower for girls than for boys. The interorbital distance normally remains small until 18 months of age, when distance gradually increases in both sexes. Interorbital growth levels off in females at age 13 years, but in males this distance continues to increase until 21 years of age (Converse et al., 1975). Interorbital distances are closely related to ethnic background. Individuals who trace their ancestry to Eskimos or Mongolians may have hypotelorism as a normal genetic variation (Awan, 1977).

Hypotelorism is uncommon. Most references list the incidence of hypotelorism as unknown, but one reference documented hypotelorism in 1 in 1220 deliveries in Taiwan (a frequency of 0.08% livebirths) (Kuo et al., 1990).

Imaging of the fetal orbits and measurements of the interorbital distance are not routine in most centers that provide antenatal sonography. Measurement of the interorbital distance is not included in the American Institute of Ultrasound in Medicine (AIUM) or American College of Obstetrics and Gynecology (ACOG) guidelines for obstetrical sonography (American College of Obstetrics and Gynecology, 2008). Fetal orbital measurements should be taken in any pregnant woman with a previously affected child, or in the setting of a facial cleft, or with a central nervous system malformation such as hydrocephalus or holoprosencephaly. When orbital hypotelorism is discovered, the finding should be taken seriously, because of its strong association with cerebral abnormalities (Trout et al., 1994). In 1982, Jeanty and colleagues determined the ocular diameter, interocular distances, and binocular distances in a group of fetuses. They proposed the use of inner and outer canthal distances as an indication of fetal growth. In another study of 1108 pregnant women, the interorbital distances were analyzed in fetuses between 7 and 38 weeks of gestation. A chart consisting of normal growth percentiles for the intermalar and interethmoidal distances was created for fetuses between 10 and 40 weeks of gestation (de Elejalde and de Elejalde, 1985). These investigators thought that the intermalar and interethmoidal distances were comparable to postnatal measurements of inner and outer canthal distances. In 1982, Mayden and colleagues constructed a nomogram from measurements of fetal inner and outer orbital diameters obtained in 180 normal pregnancies. These investigators demonstrated that the outer orbital diameter was closely related to the biparietal diameter. After constructing this nomogram, they studied an additional 463 fetuses considered to be at high risk for anomalies. They diagnosed three cases of hypotelorism with fetal orbital measurements below the 95% confidence limits. In two of these three fetuses, hypotelorism was confirmed postnatally, and the other was lost to follow-up. This nomogram was also used to examine six fetuses at risk for ocular abnormalities due to prior affected children in the family. In all six cases, normal antenatal measurements were predicted and correlated with normal neonatal interocular distances (Mayden et al., 1982). Twelve years after this report, the validity of this nomogram was tested in a high-risk antenatal population. These later investigators obtained inner and outer canthal measurements of 422 fetuses studied prospectively at gestational ages of 12 to 37 weeks (Trout et al., 1994). Six cases of hypotelorism and two cases of cyclopia were identified. For all of these affected fetuses, both the inner and outer canthal measurements fell clearly more than 2 SD below the mean. Most cases had measurements that were 3 or 4 SD below the mean and were very clearly abnormal. In all the cases of hypotelorism, there were associated intracranial or extracranial abnormalities, including holoprosencephaly, encephalocele, cleft palate, cardiac anomalies, imperforate anus, congenital diaphragmatic hernia, and digital anomalies. These investigators recommended measurement of the interorbital distance at the level of the thalamus at the same time that the biparietal diameter was measured (Figure 26-1). They stated that bony orbits were seen reliably in transabdominal scans from 12 weeks of gestation and later.