Megalocornea

Clinical Characteristics
Ocular Features: 

The corneal diameter is enlarged at birth to between 13.0 and 16.5 mm and the anterior chamber is deep.  Male patients may develop early arcus, and eventually a crocodile shagreen pattern in the cornea.  Presenile cataracts, iris thinning, and iridodenesis have also been reported.  Glaucoma does not seem to be a part of this syndrome.  The ERG has revealed mild cone system dysfunction in some patients.. 

Systemic Features: 

Isolated megalocornea is not associated with systemic disease by definition but systemic evaluation must be performed to rule out other syndromes.

Some patients have been reported to have a focal loss of white matter myelination with superior cognitive abilities.

Genetics

Only a few pedigrees have been reported.  X-linked (male only) inheritance is most common.  Carrier females do not have ocular disease.  Multiple mutations in CHRDL1 (Xq23) have been found in at least 7 families. The gene encodes ventroptin, a morphogenic protein antagonist with multiple functions including specification of topographic retinotectal projections..  The gene is expressed in corneal development, anterior segment, and retina as well as brain.

Notably, megalocornea not only occurs as an isolated trait but also may be a part of systemic syndromes such as the Marfan syndrome (154700), Down syndrome andRieger syndrome (180500 ).  It is also a part of an autosomal recessive mental retardation syndrome, sometimes called Neuhauser syndrome (249310).

Autosomal inheritance (usually recessive) has also been suggested but no locus has been found on autosomes.

Homozygous mutations in LTBP2 have been reported in consanguineous families in which sibs have congenital Megalocornea, Ectopia Lentis, and Spherophakia.

Treatment
Treatment Options: 

There is no treatment for the overall condition but correction of refractive errors, cataract surgery, and low vision aids could be helpful.
 

References
Article Title: 

Association of CHRDL1 Mutations and Variants with X-linked Megalocornea, Neuhäuser Syndrome and Central Corneal Thickness

Davidson AE, Cheong SS, Hysi PG, Venturini C, Plagnol V, Ruddle JB, Ali H, Carnt N, Gardner JC, Hassan H, Gade E, Kearns L, Jelsig AM, Restori M, Webb TR, Laws D, Cosgrove M, Hertz JM, Russell-Eggitt I, Pilz DT, Hammond CJ, Tuft SJ, Hardcastle AJ. Association of CHRDL1 Mutations and Variants with X-linked Megalocornea, Neuhauser Syndrome and Central Corneal Thickness. PLoS One. 2014 Aug 5.

PubMed ID: 
25093588

X-Linked Megalocornea Caused by Mutations in CHRDL1 Identifies an Essential Role for Ventroptin in Anterior Segment Development

Webb TR, Matarin M, Gardner JC, Kelberman D, Hassan H, Ang W, Michaelides M, Ruddle JB, Pennell CE, Yazar S, Khor CC, Aung T, Yogarajah M, Robson AG, Holder GE, Cheetham ME, Traboulsi EI, Moore AT, Sowden JC, Sisodiya SM, Mackey DA, Tuft SJ, Hardcastle AJ. X-Linked Megalocornea Caused by Mutations in CHRDL1 Identifies an Essential Role for Ventroptin in Anterior Segment Development. Am J Hum Genet. 2012 Jan 24. [Epub ahead of print].

PubMed ID: 
22284829

References

Davidson AE, Cheong SS, Hysi PG, Venturini C, Plagnol V, Ruddle JB, Ali H, Carnt N, Gardner JC, Hassan H, Gade E, Kearns L, Jelsig AM, Restori M, Webb TR, Laws D, Cosgrove M, Hertz JM, Russell-Eggitt I, Pilz DT, Hammond CJ, Tuft SJ, Hardcastle AJ. Association of CHRDL1 Mutations and Variants with X-linked Megalocornea, Neuhauser Syndrome and Central Corneal Thickness. PLoS One. 2014 Aug 5.

PubMedID: 25093588

Webb TR, Matarin M, Gardner JC, Kelberman D, Hassan H, Ang W, Michaelides M, Ruddle JB, Pennell CE, Yazar S, Khor CC, Aung T, Yogarajah M, Robson AG, Holder GE, Cheetham ME, Traboulsi EI, Moore AT, Sowden JC, Sisodiya SM, Mackey DA, Tuft SJ, Hardcastle AJ. X-Linked Megalocornea Caused by Mutations in CHRDL1 Identifies an Essential Role for Ventroptin in Anterior Segment Development. Am J Hum Genet. 2012 Jan 24. [Epub ahead of print].

PubMedID: 22284829

Khan AO, Aldahmesh MA, Alkuraya FS. Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations. Mol Vis. 2011;17:2570-9.

PubMedID: 22025892

Mackey, D. A.; Buttery, R. G.; Wise, G. M.; Denton, M. J. : Description of X-linked megalocornea with identification of the gene locus. Arch. Ophthal. 109: 829-833, 1991.

PubMedID: 2043071

Chen, J. D.; Mackey, D.; Fuller, H.; Serravalle, S.; Olsson, J.; Denton, M. J. : X-linked megalocornea: close linkage to DXS87 and DXS94. Hum. Genet. 83: 292-294, 1989.

PubMedID: 2571565

Neuhauser, G.; Kaveggia, E. G.; France, T. D.; Opitz, J. M.: Syndrome of mental retardation, seizures, hypotonic cerebral palsy and megalocorneae, recessively inherited. Z. Kinderheilk. 120: 1-18, 1975.

PubMedID: 1172332