Waardenburg anophthalmia syndrome: Report and review

To the Editor

We report on a case of Waardenburg anophthalmia syndrome, an autosomal recessive disorder comprising anopthalmia, distal limb abnormalities, and sometimes mental retardation; we review the other cases published to date.

An 8-year-old girl has been followed since she was age of 5 months (Fig. 1). She was hospitalized because of a urinary tract infection. She was born with a weight of 2,250 g to a consanguineous married couple after an uncomplicated term pregnancy. Her birth length was unknown. She was the only child of the family. At age 8 years, she weighed 17 kg (3rd centile) and was 114 cm tall (below 3rd centile). Her face was small, and she had bilateral anophthalmia, short palpebral fissures, closed eyelids, syndactyly between the 4th and 5th fingers, which were operated on, and absence of the 5th toe (Fig. 2). Her motor and mental development was normal. Laboratory findings of blood and urine were normal. X-ray examination showed proximal 4th and 5th metacarpal synostosis, hypoplasia of the 5th finger, coalition of capitate and hamate, and absence of 5th metatarsals and toes (Figs. 3 and 4). Computed tomography scan was normal. Karyotype was 46,XX.

Anophthalmia is an extreme form of microphthalmia, which can be isolated or associated with congenital abnormalities such as distal limb defects. The Waardenburg anophthalmia syndrome was first described by Waardenburg in 1961. This syndrome is a very rare autosomal recessive disorder comprising anophthalmia, which is generally bilateral, limb abnormalities such as syndactyly, brachydactyly, camptodactyly, synostosis, hip dislocation, absence, or hypoplasia of fibula, and bowed tibia [Le Merrer et al., 1988; Richieri-Costa et al., 1983; Sayli et al., 1995; Suyugül et al., 1996]. There is a vestige of the eye microscopically inside in this syndrome, and in our case we refer the clinical anophthalmia although the possibility of that condition exists. To date, approximately seven families with this syndrome have been described. The combination of ocular and limb defects together constitutes Waardenburg anophthalmia syndrome with differential diagnosis of oculo-facio-skeletal syndrome, Lenz microphthalmia syndrome, and Fraser syndrome. Those syndromes are also associated with some other anomalies, such as cerebral findings in oculo-facio-skeletal syndrome, urogenital, cardiac anomalies in Lenz microphthalmia syndrome, and urogenital, cerebral findings in fraser-cryptophthalmos syndrome. One patient of Waardenburg et al. [1961] had unilateral anophthalmia and the other had anophthalmia of one eye and microphthalmia of the other. In the Richieri-Costa et al. [1983] case the left eye was absent and the right was normal. Absence of the fifth toes and syndactyly of the fourth and fifth metacarpals are typical limb defects, which have been described by all authors in this syndrome [Le Merrer et al., 1988; Richieri-Costa et al., 1983; Sayli et al., 1995; Suyugül et al., 1996; Waardenburg, 1961]. Carpal synostosis is the other finding as hand malformation in our case. Fibula hypoplasia and bowed tibia, tarsal fusion, and valgus deformity may be seen in some cases [Le Merrer et al., 1988; Sayli et al., 1995]. Deafness and cleft palate were also described by Waardenburg [1961].

Although mental retardation is accepted as one of the main signs of the syndrome by Suyugül et al. [1996], this is not a constant finding of Waardenburg anophthalmia syndrome. It was reported in some cases, however, other cases and our case had no mental retardation [Le Merrer et al., 1988; Richieri-Costa et al., 1983; Sayli et al., 1995; Waardenburg, 1961].

Since consanguinity, which has been previously described in all cases is also seen in the presented case, autosomal recessive transmission seems substantiated. Two of seven case reports, which have been described since Waardenburg's case in 1961, are from Turkey [Sayli et al., 1995; Suyugül et al., 1996]. Higher incidence of consanguineous marriages is considered to be the reason for that the disorder is seen more often in Turkey.