Syndromic Microphthalmia Type 5

Syndromic microphthalmia, type 5 is characterized by the association of a range of ocular anomalies (anophthalmia, microphthalmia and retinal abnormalities) with variable developmental delay and central nervous system malformations.

Epidemiology

Less than 20 cases have been reported in the literature so far.

Clinical description

The clinical picture is highly variable, even between affected members of the same family. Ocular findings ranged from bilateral anophthalmia, to severe or mild bi- or unilateral microphthalmia and retinal dystrophy. MRI may reveal optic nerve aplasia/hypoplasia, hippocampal malformations, structural abnormalities of the pituitary gland, and agenesis of the corpus callosum. Severe developmental delay was noted in some patients, whilst others showed normal cognitive development. Pituitary dysfunction, leading to growth hormone deficiency and short stature, or combined pituitary hormone deficiency (CPHD), has also been reported.

Etiology

The syndrome is caused by heterozygous mutations in the OTX2 gene (14q22.3).

Differential diagnosis

A similar phenotype with bilateral anophthalmia and pituitary abnormalities (with additional findings of limb defects, ear anomalies and facial dysmorphism) is found in patients carrying a deletion encompassing the OTX2 gene. Patients with the full clinical spectrum of ocular anomalies, central nervous system abnormalities and pituitary abnormalities also show significant overlap with septooptic dysplasia (see this term).