Sir,

The association of Peters' anomaly with persistent hyperplastic primary vitreous (PHPV) has been reported clinically and histopathologically,1 but a genetic cause for the clinically uncommon complexation of these two malformations has not been reported.

A male child (3090 g) was born by normal gestation and delivery, and had no systemic abnormalities. His parents noted leukocoria in the right eye at the age of 7 days. Slit-lamp examination and ultrasound biomicroscopy showed central corneal opacity with anterior iris synechia, a shallow anterior chamber, lens subluxation, and elongated ciliary processes in the right eye (Figure 1a–c). Computed tomography showed right microphthalmos.

Figure 1
figure 1

Slit-lamp, ultrasound biomicroscopy, and endoscopic findings of the right eye. (a and b) Slit-lamp photograph shows central corneal opacity with anterior iris synechia and lens subluxation. Zonule of Zinn is lacking and elongated ciliary processes (arrowheads) are observed nasally. (c) Ultrasound biomicroscopy (UBM) shows anterior iris synechia towards the central cornea (arrows), anterior displacement of the lens (asterisk) between the cornea and the elongated ciliary process (arrowheads), which was also observed by slit-lamp examination (b, arrowheads). (d) A persistent hyaloid artery is observed from the optic disc to the fibrovascular tissue behind the lens.

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Pars plana lensectomy and anterior vitrectomy were performed in the right eye at the age of 7 months to manage the pupillary block. Endoscopic findings revealed a persistent hyaloid artery towards the fibrovascular tissue behind the lens (Figure 1d). On the basis of these findings, we diagnosed the child with Peters' anomaly-complicated PHPV.

After obtaining informed consent, molecular genetic analysis of the PITX2 gene by direct sequencing of all the coding regions revealed a novel 649C>A mutation in the proband (Figure 2). This substitution was not detected either in parents or in 72 healthy controls.

Figure 2
figure 2

Electrophorogram of the sense strand of genomic DNA. (Top) A novel heterozygous missense mutation of C to A at 649 bp in PITX2 (Pro217Thr) from the patient. The arrow indicates the portion of the mutation that is absent in a healthy control (bottom).

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We postulate that the novel PITX2 gene mutation leads to migratory disorders of neural crest cells, which may result in both Peters' anomaly and PHPV, given the common mechanism underlying migratory disorders of neural crest cells and that which occurs during the critical period described for the diseases.2 This hypothesis is consistent with recent findings that PITX2 expression in neural crest cells is observed not only in the anterior segment but also in the vitreous cavity at embryonic day 12.5 in mice.3 Moreover, the deletion of 6p25, on which FOXC1 is located, which has a functional link with PITX2,4 was reported to be associated with PHPV and Axenfeld–Rieger syndrome,5 a syndrome thought to present the same spectrum of defects as Peters' anomaly.

We should carefully inspect the posterior segment in addition to the anterior segment in patients with congenital central corneal opacity. Molecular genetic analysis of PITX2 can help provide an accurate diagnosis of the diseases.