Microphthalmia

Microphthalmia (Greek: μικρός mikros = small; ὀφθαλμός ophthalmos = eye), also referred as microphthalmos, is a developmental disorder of the eye in which one (unilateral microphthalmia) or both (bilateral microphthalmia) 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 (CMV), but the evidence is inconclusive. Genetic causes of microphthalmia include chromosomal abnormalities (Trisomy 13 (Patau syndrome), Triploid Syndrome, 13q deletion syndrome, and Wolf-Hirschhorn Syndrome) 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	300166	MCOPS2
BMP4	Induces cartilage and bone formation	607932	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 (sex determining region Y)-box 2	206900	MCOPS3
VSX1	visual system homeobox 1 VSX1	visual system homeobox 1
RAB18	Ras-related protein 18
VSX2 (CHX10)	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 (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 microphthalmia. 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.

Epidemiology

The most extensive epidemiological survey on this congenital malformation has been carried out by Dharmasena et al and using English National Hospital Episode Statistics, they calculated the annual incidence of anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus from 1999 to 2011. According to this study the annual incidence of congenital microphthalmia in the United Kingdom was 10.8 (8.2 to 13.5) in 1999 and 10.0 (7.6 to 12.4) in 2011.

See also

• Abdominal Musculature Absent With Microphthalmia And Joint Laxity

Further reading

• GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
• GeneReviews/NCBI/NIH/UW entry on Microphthalmia with Linear Skin Defects Syndrome
• OMIM-Online Mendelian Inheritance in Man

External links

Classification	ICD-10: Q11.2 ICD-9-CM: 743.1 DiseasesDB: 29618
External resources	eMedicine: oph/572 GeneReviews: Anophthalmia / Microphthalmia Overview