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Left Unilateral Microphthalmia
SpecialtyMedical genetics Edit this on Wikidata

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. Microphthalmia is a distinct condition from anophthalmia and nanophthalmia. Although sometimes referred to as 'simple microphthalmia', nanophthalmia is a condition in which the size of the eye is small but no anatomical alterations are present.[1][2]


Microphthalmia is congenital disorder in which the globe of the eye is as unusually small and structurally disorganized.[1][3] While the axis of an adult human eye has an average length of about 23.8 mm, a diagnosis of microphthalmia generally corresponds to an axial length below 21 mm in adults.[2][4] Additionally, the diameter of the cornea is about 9-10.5 mm in affected newborns and 10.5-12 mm in adults with the condition.[2] The presence of a small eye within the orbit can be a normal incidental finding but in many cases it is atypical and results in visual impairment. The prevalence of this conditions is around 1 in 10,000 births, and it affects roughly 3-11% of blind children.[2][5][6]


Microphthalmia in newborns is sometimes associated with fetal alcohol syndrome[1] 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.[citation needed] 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[7] Induces cartilage and bone formation 607932 MCOPS6
CRYBA4 crystallin, beta A4
FOXE3 forkhead box E3
GDF3[8] growth differentiation factor 3
GDF6[8] 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.[citation needed]


Depiction of Infant with Microphthalmia

Microphthalmia is often diagnosed soon after birth. An initial diagnosis usually occurs after the eyes are inspected through the lids.[2] In addition to visual examinations, measurements of the cornea are used in the diagnosis of this condition.[2] An ultrasound may also be conducted to confirm whether the axial length of the eye is clinically below average (i.e. at least 2 standard deviations below the age-adjusted mean).[2][4]

When a case of microphthalmia is detected, the patient should visit an eye specialist as soon as possible. It is important for an ophthalmologist to conduct a thorough examination within 2 weeks after birth.[9] The ophthalmologist will confirm the preliminary diagnosis and look for signs of other anomalies in both eyes. These abnormalities may include coloboma, optic nerve hypoplasia, retinal dystrophy, and cataract.[9] Ultrasound may also be used to determine the presence of any internal eye issues, which may not otherwise be visible.[9] It is possible for individuals with microphthalmia to have some vision in the affected eye(s). For this reason, the vision of infants with microphthalmia should be evaluated early on, even in severe cases.[9] Pediatric visions tests along with electro-diagnostics are typically used to assess visual acuity.[9]


Microphthalmia cannot be cured. When the eye function is maintained, a patient's vision can be improved (sometimes up to good state) by plus lenses, as a small eye is usually hyperopic.[citation needed]


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.[6]

See also[edit]


  1. ^ a b c "Definition of Microphthalmia". MedicineNet. Retrieved 2009-01-01.
  2. ^ a b c d e f g Verma AS, Fitzpatrick DR (November 2007). "Anophthalmia and microphthalmia". Orphanet Journal of Rare Diseases. 2 (1): 47. doi:10.1186/1750-1172-2-47. PMC 2246098. PMID 18039390.
  3. ^ Williams AL, Bohnsack BL (June 2015). "Neural crest derivatives in ocular development: discerning the eye of the storm". Birth Defects Research. Part C, Embryo Today. 105 (2): 87–95. doi:10.1002/bdrc.21095. PMC 5262495. PMID 26043871.
  4. ^ a b Groot AL, Kuijten MM, Remmers J, Gilani A, Mourits DL, Kraal-Biezen E, et al. (February 2020). "Classification for treatment urgency for the microphthalmia/anophthalmia spectrum using clinical and biometrical characteristics". Acta Ophthalmologica. 98 (5): 514–520. doi:10.1111/aos.14364. PMC 7497250. PMID 32100474.
  5. ^ "Microphthalmia: MedlinePlus Genetics". medlineplus.gov. Retrieved 2021-04-16.
  6. ^ a b Dharmasena A, Keenan T, Goldacre R, Hall N, Goldacre MJ (June 2017). "Trends over time in the incidence of congenital anophthalmia, microphthalmia and orbital malformation in England: database study". The British Journal of Ophthalmology. 101 (6): 735–739. doi:10.1136/bjophthalmol-2016-308952. PMID 27601422.
  7. ^ "Genetics Home Reference". National Library of Medicine. Retrieved 19 January 2015.
  8. ^ a b "Genetics Home Reference". National Library of Medicine. Retrieved 19 January 2015.
  9. ^ a b c d e Ragge, N K; Subak-Sharpe, I D; Collin, J R O (October 2007). "A practical guide to the management of anophthalmia and microphthalmia". Eye. 21 (10): 1290–1300. doi:10.1038/sj.eye.6702858. ISSN 0950-222X.

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