Microphthalmia
Encyclopedia
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
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 maybe autosomal dominant, autosomal recessive or X linked.
Genes that have been implicated in microphthamia include many transcription and regulatory factors. Those identified from family studies include the following:
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 eye ball) 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 mammal
s 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 phenotype
s of MITF mutant mice.
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
The major causes for this disorder are genetic but environmental factors have also been implicated such as exposure to radiation, chemicals, or viruses. Microphthalmia in newborns is sometimes associated with fetal alcohol syndromeFetal alcohol syndrome
Fetal alcohol syndrome is a pattern of mental and physical defects that can develop in a fetus in association with high levels of alcohol consumption during pregnancy. Current research also implicates other lifestyle choices made by the prospective mother...
or infections during pregnancy, particularly herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
, rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
and cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
(CMV), but the evidence is inconclusive. Genetic causes of microphthalmia include chromosomal abnormalities (trisomy 13 (Patau syndrome
Patau syndrome
Patau syndrome, also known as trisomy 13 and trisomy D, is a chromosomal abnormality, a syndrome in which a patient has an additional chromosome 13 due to a nondisjunction of chromosomes during meiosis. Some are caused by Robertsonian translocations...
), Triploid Syndrome
Triploid Syndrome
Triploid Syndrome is an extremely rare chromosomal disorder. Individuals with triploid syndrome have three of every chromosome for a total of sixty-nine rather than the normal forty-six chromosomes....
, and Wolf-Hirschhorn Syndrome
Wolf-Hirschhorn syndrome
Wolf–Hirschhorn syndrome , also known as chromosome deletion 4p syndrome, Pitt-Rogers-Danks syndrome or Pitt syndrome, was first described in 1961 by Americans Herbert L...
) or monogenetic Mendelian disorders. The latter maybe autosomal dominant, autosomal recessive or X linked.
Genes that have been implicated in microphthamia include many transcription and regulatory factors. Those identified from family studies include the following:
| HGNC symbol | Description | OMIM | Type |
|---|---|---|---|
| BCOR BCOR BCL-6 corepressor is a protein that in humans is encoded by the BCOR gene.Mutations in the BCOR gene cause a form of syndromic microphthalmia called MCOPS2. This syndrome incorporates microphthalmia, congenital cataracts, cardiac defects, dental defects and skeletal anomalies... |
BCL6 BCL6 B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.- Function :The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain... corepressor |
MCOPS2 | |
| CRYBA4 CRYBA4 Beta-crystallin A4 is a protein that in humans is encoded by the CRYBA4 gene.-Further reading:... |
crystallin, beta A4 | ||
| FOXE3 FOXE3 Forkhead box protein E3 also known as forkhead-related transcription factor 8 is a protein that in humans is encoded by the FOXE3 gene located on the short arm of chromosome 1.- Function :... |
forkhead box E3 | ||
| GDF6 GDF6 Growth differentiation factor 6 is a protein that in humans is encoded by the GDF6 gene.belonging to the transforming growth factor beta superfamily that may regulate patterning of the ectoderm by interacting with bone morphogenetic proteins, and control eye development.... |
growth differentiation factor 6 | ||
| MITF | microphthalmia-associated transcription factor | ||
| OTX2 | orthodenticle homeobox 2 | ||
| PAX6 PAX6 Paired box protein Pax-6 also known as aniridia type II protein or oculorhombin is a protein that in humans is encoded by the PAX6 gene.- Function :PAX6 is a member of the Pax gene family... |
paired box 6 | ||
| PITX3 PITX3 Pituitary homeobox 3 is a protein that in humans is encoded by the PITX3 gene.-Further reading:... |
Paired-like homeodomain transcription factor 3 | ||
| RAX RAX Radio Aurora Explorer is the first National Science Foundation sponsored CubeSat mission . The RAX mission is a joint effort between in Menlo Park, California and the in Ann Arbor, Michigan. The chief scientist, Dr. Hasan Bahcivan, led his team at SRI to develop the payload while the chief... |
retina and anterior neural fold homeobox | ||
| SHH SHH SHH can refer to:* Summer Heights High, an Australian TV series* Sonic hedgehog, an important protein during vertebrate organogenesis* Students Helping Honduras, an international non-governmental organization operating in the U.S. and Honduras... |
sonic hedgehog homolog | ||
| SIX6 | SIX homeobox 6 | ||
| SOX2 SOX2 SRY -box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells.... |
SRY (sex determining region Y)-box 2 | MCOPS3 | |
| VSX1 VSX1 Visual system homeobox 1 is a protein that in humans is encoded by the VSX1 gene.The protein encoded by this gene contains a paired-like homeodomain and binds to the core of the locus control region of the red/green visual pigment gene cluster. The encoded protein may regulate expression of the... |
visual system homeobox 1 | ||
| VSX2 VSX2 Visual system homeobox 2 is a protein that in humans is encoded by the VSX2 gene.-Further reading:... (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 eye ball) 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 mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s the failure of expression of the transcription factor, MITF (microphthalmia-associated transcription factor
Microphthalmia-associated transcription factor
Microphthalmia-associated transcription factor is a basic helix-loop-helix leucine zipper transcription factor involved in melanocyte and osteoclast development.-Clinical significance:...
), in the pigmented retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
prevents this structure from fully differentiating. This in turn causes a malformation of the choroid fissure
Choroid fissure
The choroid is the middle, vascular coat of the eye which resides between the sclera and the retina. Early in development the choroid fissure is the slit observed between the two edges of the eye cup. During development it is through the choroid fissure that the retinal vessels enter the eye and...
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
Waardenburg syndrome
Waardenburg syndrome Waardenburg syndrome Waardenburg syndrome (also Waardenburg Shah Syndrome, Waardenburg-Klein syndrome, Mende's syndrome II, Van der Hoeve-Halbertsma-Waardenburg syndrome, Ptosis-Epicanthus syndrome, Van der Hoeve-Halbertsma-Gualdi syndrome, Waardenburg type Pierpont,[5] Van...
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
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
with mutations in this gene are hypopigmented
Hypopigmentation
Hypopigmentation is the loss of skin color. It is caused by melanocyte or melanin depletion, or a decrease in the amino acid tyrosine, which is used by melanocytes to make melanin.-Treatments:...
in their fur. The identification of the genetics of WS type 2 owes a lot to observations of phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s of MITF mutant mice.
External links
- GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
- Parent Support group for parents with Anophthalmic and Microphthalmic children MAPS
- Anophthalmia and Microphthalmia Resource Guide from the National Eye Institute (NEI).
- GeneReviews/NCBI/NIH/UW entry on Microphthalmia with Linear Skin Defects Syndrome
- MACS The Micro and Anophthalmic Childrens Society - Offers support and Information to families in the UK and around the world
- EnsemblEnsemblEnsembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent completion of the Human Genome Project...
- http://HGNCHUGO Gene Nomenclature Committee
- OMIM-Online Mendelian Inheritance in Man