A Medline/PubMed search was performed using the terms "nanophthalmos," "ocular development," and "genetics" and their combinations.
Nanophthalmos is a special subtype of microphthalmia, in which the eye, although small, has preserved functionality and organization (Figure 1) [13, 14].
Another diagnostic issue that has been debated in the literature is the distinction between nanophthalmos and posterior microphthalmos.
They also reported different tendencies to complications: the incidence of angle-closure glaucoma was 69.23% in the nanophthalmos group versus 0% in the posterior microphthalmos group, while the incidence of macular folds was 0% versus 24%, respectively .
However, it is unclear whether the abnormal scleral structure is a primary or secondary effect of the genetic changes that induce nanophthalmos as many of the genes implicated in this condition are expressed in retina and retinal pigment epithelium [14, 29-32].
In summary, the described anatomical features and histopathology of the nanophthalmic eye explain the severe visual consequences in individuals with nanophthalmos. If the axial hyperopia is not corrected in early childhood, then this results in irreversible amblyopia.
Nanophthalmos occurs due to arrested development of the eye in the early stages of embryogenesis.
To date, five genetic loci (Table 3) were reported to be linked to nanophthalmos: NNOS 2 is related to mutations in membrane frizzled-related protein (MFRP); NNOS 4 is related to mutations in TMEM98; MCOP6 is related to mutations in serine protease 56 (PRSS56) [50, 51]; and NNOS 1 and 3 were localized to chromosomal regions only (11p12-11q13 and 2q11-q14) [26, 29, 30].
A significant number of cases of recessive nanophthalmos have been assigned to mutations in the membrane-type frizzled-related protein gene (MFRP, OMIM 606227) .