Prenatal sonographic appearance of cryptophthalmos in Fraser syndrome

Abstract

Cryptophthalmos (hidden eye) is characterized by the continuous passage of skin from the forehead to the cheek and absence of the palpebral fissure. Cryptophthalmos is the leading feature of Fraser syndrome and has been described in 84 to 93% of affected patients1,2. Cryptophthalmos–syndactyly syndrome or Fraser syndrome is an inherited disorder characterized by variable expression of cryptophthalmos, renal agenesis, laryngeal stenosis, syndactyly, abnormalities of the ears and external genitalia and other minor anomalies. Because of the marked variability of expression in patients with cryptophthalmos, Thomas et al.1 established strict diagnostic criteria (major and minor) for the diagnosis of Fraser syndrome after birth. They outlined the following major criteria: cryptophthalmos, syndactyly, abnormal genitalia and sib with cryptophthalmos syndrome. The minor criteria are malformations of the nose, ears, or larynx, cleft lip and/or palate, umbilical hernia, renal agenesis, skeletal defects and mental retardation. Cases are diagnosed on the basis of at least two major criteria and one minor criterion or on the basis of one major criterion and at least four minor criteria. Because of the difficulty of demonstrating the major criteria, the prenatal diagnosis of the syndrome relies almost entirely on the detection of some of the easily detectable minor criteria like laryngeal atresia and renal agenesis. Many of the reports of prenatal diagnosis of this syndrome have been in the follow-up of a pregnancy with a previous sibling having had the same syndrome3–7. Of all the reports regarding the diagnosis of Fraser syndrome in families with a negative history, the final diagnosis was reached prenatally only in five instances8–11. In four of these reports the prenatal sonographic findings reported were obstructive uropathy8, hydrocephalus8, severe oligohydramnios9 and pulmonary hyperplasia10, but a definitive prenatal diagnosis of Fraser syndrome was not made. Maruotti et al.11 reported the prospective prenatal diagnosis of Fraser syndrome in a fetus at 21 weeks’ gestation based on oligohydramnios, laryngeal atresia, bilateral renal agenesis, bilateral microphthalmos and rhizomelic shortening of bones. In this report we describe the high-resolution sonographic appearance of cryptophthalmos and abnormality of the ocular globes in Fraser syndrome. A 24-year-old woman, gravida 2 para 1, was referred for sonography to rule out fetal anomalies. Her first male child had been delivered normally at term, but died on the second day owing to congenital heart disease. She was in her 26th week of gestation. Sonography was performed using convex 2–5-MHz and 4–7-MHz and linear 5–12MHz probes. Fetal biometry corresponded to a gestational age of 24 weeks, but the amniotic fluid volume was normal. The fetus showed agenesis of the right kidney, a small omphalocele and unilateral microphthalmos. On high-resolution ultrasound examination skin was seen to be continuous over the eyeballs on both sides and the palpebral fissure could not be identified (Figure 1). Echoes from the lens and ciliary apparatus could not be seen within the eyeballs, which revealed a single cavity (Figure 1). The fetus was also found to have bilateral cutaneous syndactyly of all fingers. The ears were small and deformed. The penis was short and lacked preputial cover. A prenatal diagnosis of Fraser syndrome was made and the parents chose to terminate the pregnancy. Externally the fetus showed bilateral cryptophthalmos, low frontal hairline (Figure 2), and bilateral low-set ears with abnormal pinna, broad abnormal nose, micrognathia, normal scrotum, micropenis, imperforate anus and syndactyly of the fingers. On autopsy the right kidney was absent and the left kidney was normal. There was a small omphalocele containing a Meckel’s diverticulum. The right eyeball was smaller than the left. On histopathology the eyeballs revealed only portions of lenses and ciliary bodies, and retinal dysplasia on both sides. These features confirmed the prenatal diagnosis of Fraser syndrome. In the longitudinal scan of the orbit of a normal fetus, the palpebral fissure is seen as a thin gap between the upper and lower eyelids (Figure 1c). In the fetus with Fraser syndrome described here, the cryptophthalmos