Microphthalmia
Microphthalmia, also referred as microphthalmos, is a developmental disorder of the eye in which one or both eyes are abnormally small and have anatomic malformations. It is different from nanophthalmos in which the eye is small in size but has no anatomical alterations.
Presentation
The presence of a small eye within the orbit can be a normal incidental finding but in most cases it is abnormal and results in blindness. The incidence is 14 per 100,000 and the condition affects 3-11% of blind children.Causes
Microphthalmia in newborns is sometimes associated with fetal alcohol syndrome or infections during pregnancy, particularly herpes simplex virus, rubella and cytomegalovirus, but the evidence is inconclusive. Genetic causes of microphthalmia include chromosomal abnormalities or monogenetic Mendelian disorders. The latter may be autosomal dominant, autosomal recessive or X linked.The following genes have been implicated in microphthalmia, many of which are transcription and regulatory factors:
| HGNC symbol | Description | OMIM | Type |
| BCOR | BCL6 corepressor | MCOPS2 | |
| BMP4 | Induces cartilage and bone formation | MCOPS6 | |
| CRYBA4 | crystallin, beta A4 | - | - |
| FOXE3 | forkhead box E3 | - | - |
| GDF3 | growth differentiation factor 3 | - | - |
| GDF6 | growth differentiation factor 6 | - | - |
| MITF | microphthalmia-associated transcription factor | - | - |
| OTX2 | orthodenticle homeobox 2 | - | - |
| PAX6 | paired box 6 | - | - |
| PITX3 | Paired-like homeodomain transcription factor 3 | - | - |
| RAX | retina and anterior neural fold homeobox | - | - |
| SHH | sonic hedgehog homolog | - | - |
| SIX6 | SIX homeobox 6 | - | - |
| SOX2 | SRY -box 2 | MCOPS3 | |
| VSX1 | visual system homeobox 1 VSX1 | visual system homeobox 1 | - |
| RAB18 | Ras-related protein 18 | - | - |
| VSX2 | visual system homeobox 2 | - | - |
How these genes result in the eye disorder is unknown but it has been postulated that interference with the process of eye growth after birth may be involved in contrast to anophthalmia which originates much earlier during foetal development. SOX2 has been implicated in a substantial number of cases and in many other cases failure to develop the ocular lens often results in microphthalmia. Microphthalmia-associated transcription factor located on chromosome 14q32 is associated with one form of isolated microphthalmia, in the pigmented retina prevents this structure from fully differentiating. This in turn causes a malformation of the choroid fissure of the eye, resulting in the drainage of vitreous humor fluid. Without this fluid, the eye fails to enlarge, thus the name microphthalmia.The gene encoding the microphthalmia-associated transcription factor is a member of the basic helix-loop-helix-leucine zipper family. Waardenburg syndrome type 2 in humans is also a type of microphthalmia syndrome. Mutations in MITF gene are thought to be responsible for this syndrome. The human MITF gene is homologous to the mouse MITF gene ; mouse with mutations in this gene are hypopigmented in their fur. The identification of the genetics of WS type 2 owes a lot to observations of phenotypes of MITF mutant mice.