Microphthalmia
Microphthalmia also referred to as
microphthalmos,
nanophthalmia or
nanophthalmos,
is a developmental disorder of the eye that literally means small eye
(micros = small; ophthalmos = eye). One (Unilateral Microphthalmia) or
both (Bilateral Microphthalmia) eyes may be involved.
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.
Microphthalmia in newborns is sometimes associated with
fetal alcohol syndrome or infections during pregnancy, particularly
herpes simplex virus,
rubella and
cytomegalovirus (CMV), but the evidence is inconclusive. Genetic causes of microphthalmia include chromosomal abnormalities (
trisomy 13 (
Patau syndrome),
Triploid Syndrome, and
Wolf-Hirschhorn Syndrome)
or monogenetic Mendelian disorders. The latter may be autosomal
dominant, autosomal recessive or X linked. Genes that have been
implicated in microphthamia include many transcription and regulatory
factors.
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 (absence of eyeball) which
originates much earlier during foetal development. SOX2 has been
implicated in a substantial number (10-15%) of cases and in many other
cases failure to develop the ocular lens often results in microphthamia.
Microphthalmia-associated transcription factor (MITF) located on
chromosome 14q32 is associated with one form of isolated microphthalmia
(MCOP1. In
mammals the failure of expression of the transcription factor, MITF (
microphthalmia-associated transcription factor), 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 (MITF) is a member of the
basic helix-loop-helix-leucine zipper (bHLH-ZIP) family.
Waardenburg syndrome type 2 (WS 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 (aka mouse mi or microphthalmia 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.