Hypertelorism is a condition in which a larger-than-average distance exists between the orbits. The distances between the medial canthi and pupils are also increased (Kirkham et al., 1975). The term was first used by Greig in 1924, who described hypertelorism as a “great breadth between the eyes.” The orbits represent a bridge between the face and the cranium. Seven different bones are required to form the orbit (frontal, zygomatic, sphenoid, ethmoidal, maxillary, lacrimal, and palatine) (Dollfus and Verloes, 2004).

Ocular hypertelorism is defined as an increased distance between the medial orbital walls. This can be demonstrated either radiographically or clinically by an increased interpupillary distance. If the interpupillary distance is greater than 2 SD above the mean for the patient’s age, hypertelorism is said to exist (Brodsky et al., 1990). More recently, it has been recommended that the diagnosis of hypertelorism be made radiographically by interorbital measurements. The difficulty with using intercanthal distance to define hypertelorism is that soft tissue changes of the face can increase the inter-canthal distance without affecting the interorbital distance (Trout et al., 1994). Telecanthus is an increased distance between the inner canthi. This can either be primary, defined as an increase in soft tissue with normal interpupillary and interbony distance, or secondary, which is really orbital hypertelorism, with an increased interbony or interpupillary distance (Murphy and Laskin, 1990). The major concern regarding the fetal finding of hypertelorism is its association with median facial and brain defects, such as encephalocele, facial cleft, and craniosynostosis.

Hypertelorism is rare. Its exact incidence is unknown. Hypertelorism may occur as an isolated condition or in association with other anomalies.

Imaging of the fetal orbits and measurements of the interorbital distance are not routinely performed in most centers that offer targeted fetal sonographic studies. Measurement of the fetal interorbital distance is not included in either 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 performed in any pregnant woman known to have had a previously affected child with a condition associated with hypertelorism, such as Waardenburg, Opitz or Noonan syndromes. Detection of fetal hypertelorism in any structural survey should alert the sonographer to the possibility of other anomalies.

In 1985, de Elejalde and de Elejalde studied 1108 pregnant women and measured the interorbital distances in fetuses between 7 and 38 weeks of gestation. They derived normal growth percentiles for the intermalar and interethmoidal distances for fetuses between 10 and 40 weeks of gestation. The intermalar and interethmoidal distances were comparable to the postnatal measurements of inner and outer canthal distances. In 1982, Mayden et al. described fetal inner and outer orbital diameter measurements in 180 normal pregnancies. The outer orbital diameter was demonstrated to be closely related to the biparietal diameter. Fetal orbits were identified in three different head positions, including occipitotransverse, occipitoposterior, and occipitoanterior. Twelve years after this report, the validity of this nomogram was tested in a high-risk antenatal population by another group of investigators, who obtained inner and outer orbital measurements from 422 fetuses between 12 and 37 weeks of gestation (Trout et al., 1994). This group identified three cases of hypertelorism, with inner orbital measurements above the 95th percentile for gestational age and outer orbital distances within the normal limits but near the 95th percentile for gestational age. In the three cases of hypertelorism identified, all fetuses had serious associated abnormalities, including cleft palate, diaphragmatic hernia, imperforate anus, porencephaly, encephalocele, and truncus arteriosus. The three fetuses with hypertelorism were all diagnosed between 20 and 33 weeks of gestation. These investigators recommended routine measurement of the interorbital distance at the level of the thalamus at the same time that the conventional biparietal diameter measurement was taken. They measured outer orbital diameter from outer-to-outer bony margins of the orbit, whereas the inner orbital diameter was measured from inner-to-inner bony margin of the orbits. The bony orbits were seen reliably from 12 weeks of gestation onward. These investigators stressed that it was the inner orbital diameter measurement that was most clearly associated with postnatal hypertelorism. The three affected fetuses described in this study had inner orbital diameter measurements that were more than 2 SD from the mean for gestational age, whereas the outer orbital diameter measurements were borderline high.

In another report of 1600 fetuses screened by transvaginal sonography at 12 to 18 weeks of gestation, 8 ocular abnormalities were found, but no cases of hypertelorism were described (Bronshtein et al., 1991). To date, there have been no reports of fetal hypertelorism in the first trimester.

In one case report, a fetus at 20 weeks of gestation was diagnosed with Opitz syndrome (Hogdall et al., 1989). This syndrome consists primarily of hypertelorism and hypospadias, with either X-linked or autosomal dominant patterns of inheritance. In this report, the fetus was described as an “atrisk” member of a large kindred affected with the autosomal dominant form of Opitz syndrome. At 18 weeks of gestation, a prenatal sonogram was within normal limits. At that time, the outer orbital measurement was 30 mm (the normal mean for gestational age is 29 mm; range, 24–33 mm). The inner orbital measurement was 15 mm (mean for gestational age, 11 mm; range, 8–15 mm). At 20 weeks, the study was repeated and a small phallus with hypospadias was noted. In addition, the outer orbital measurement was 36 mm (mean for gestational age, 33 mm; range, 28–37 mm) (Figure 25-1). The inner orbital measurement was 17 mm (mean for gestational age, 13 mm; range, 10–16 mm). Because of the provisional diagnosis of an affected fetus with Opitz syndrome, the pregnancy was terminated. Perinatal autopsy studies revealed widely separated eyes and an enlarged fourth ventricle, as well as hypospadias, and imperforate anus. Thus, the fetus was confirmed as affected. This study also reinforced the findings of Trout et al. (1994), who determined that the inner orbital measurement is the more sensitive indicator of hypertelorism.

More recently, three-dimensional (3D) ultrasound imaging has been used to improve visualization of the fetal face. This has been especially helpful in the diagnosis of frontonasal dysplasia (Sleurs et al., 2004) and Binder syndrome (Cook et al., 2000).

Hypertelorism occurs in more than 550 disorders (Dollfus and Verloes, 2004). Hypertelorism is strongly associated with other abnormalities, especially of the frontal part of the brain, such as encephalocele and dacrocystocele. A number of conditions are associated with hypertelorism, and these are summarized in Table 25-1. Most significantly, these consist of chromosomal abnormalities, single-gene disorders, developmental abnormalities of the skull, such as craniosynostosis, and midface abnormalities such as frontonasal dysplasia.