Microphthalmia, AR Clinical CharacteristicsOcular Features: The most consistent feature associated with mutations in the VSX2 gene is, of course, microphthalmia/anophthalmia. Other anomalies include dysplasia of the retina, cataracts and/or dislocated lenses, and iris anomalies ranging from hypoplasia to colobomas and absence of the pupils. Colobomas may also involve the posterior uveal tract as well as the optic nerve. The majority of patients are blind. Systemic Features: No systemic features are associated. GeneticsThis is an autosomal recessive disorder resulting from mutations in the VSX2 (formerly CHX10) gene located at 14q24.3. The gene is expressed in progenitor cells of the developing neuroretina and in inner nuclear cells of the adult retina. Most parents are consanguineous. Pedigree: Autosomal recessiveTreatmentTreatment Options: None other than rehabilitation. ReferencesArticle Title: VSX2 mutations in autosomal recessive microphthalmia Reis LM, Khan A, Kariminejad A, Ebadi F, Tyler RC, Semina EV. VSX2 mutations in autosomal recessive microphthalmia. Mol Vis. 2011;17:2527-32. PubMed ID: 2197693 CHX10 mutations cause non-syndromic microphthalmia/ anophthalmia in Arab and Jewish kindreds Bar-Yosef U, Abuelaish I, Harel T, Hendler N, Ofir R, Birk OS. CHX10 mutations cause non-syndromic microphthalmia/ anophthalmia in Arab and Jewish kindreds. Hum Genet. 2004 Sep;115(4):302-9. PubMed ID: 15257456 Autosomal recessive colobomatous microphthalmia Zlotogora J, Legum C, Raz J, Merin S, BenEzra D. Autosomal recessive colobomatous microphthalmia. Am J Med Genet. 1994 Feb 1;49(3):261-2. PubMed ID: 8209881 Read more about Microphthalmia, AR
VSX2 mutations in autosomal recessive microphthalmia Reis LM, Khan A, Kariminejad A, Ebadi F, Tyler RC, Semina EV. VSX2 mutations in autosomal recessive microphthalmia. Mol Vis. 2011;17:2527-32. PubMed ID: 2197693
CHX10 mutations cause non-syndromic microphthalmia/ anophthalmia in Arab and Jewish kindreds Bar-Yosef U, Abuelaish I, Harel T, Hendler N, Ofir R, Birk OS. CHX10 mutations cause non-syndromic microphthalmia/ anophthalmia in Arab and Jewish kindreds. Hum Genet. 2004 Sep;115(4):302-9. PubMed ID: 15257456
Autosomal recessive colobomatous microphthalmia Zlotogora J, Legum C, Raz J, Merin S, BenEzra D. Autosomal recessive colobomatous microphthalmia. Am J Med Genet. 1994 Feb 1;49(3):261-2. PubMed ID: 8209881
Cornea Plana Clinical CharacteristicsOcular Features: Enlargement of the cornea with flattening is characteristic of cornea plana although corneal diameters vary widely. Corneal thinning may be present. The mean corneal refraction value at the horizontal median has been measured at 37.8 D for the dominant form (CNA 1) of the disease, compared with 29.9 D for the recessive form (CNA 2) and 43.4 D for controls accounting for the hyperopia found among many patients. The limbal margin may be widened with blurring of the corneolimbal junction. Recessive cases can often be distinguished from the dominant ones by the presence of a central 5 mm area of thickening and clouding. Recessively inherited cases are also more likely to have anterior synechiae and other iris anomalies. Early onset arcus has been reported. Vision in mild cases may be as good as 20/25 or 20/30 but considerably worse in recessive cases with central opacification. Glaucoma may occur in older individuals. Systemic Features: None reported. GeneticsMultiple families in Finland have been reported with inheritance patterns suggesting autosomal recessive inheritance (CNA2). The gene has been mapped to chromosome 12 (12q21) in a region containing the KERA gene. A Cuban family with autosomal dominant cornea plana (CDA1) also yielded linkage to 12q where the recessive gene is located. However, this locus could be excluded in two Finnish families suggesting that at least 3 autosomal mutations may be responsible. Pedigree: Autosomal dominantAutosomal recessiveTreatmentTreatment Options: Correction of the hyperopia may be helpful. Patients need to be followed and treated for glaucoma if it develops. Outcomes of penetrating keratoplasty are not available but the procedure carries increased risk since the stroma is often thinner than normal. ReferencesArticle Title: Dominantly and recessively inherited cornea plan congenita map to the same small region of chromosome 12. Tahvanainen, E.; Villanueva, A. S.; Forsius, H.; Salo, P.; de la Chapelle, A. : Dominantly and recessively inherited cornea plana congenita map to the same small region of chromosome 12. Genome Res. 6: 249-254, 1996. PubMed ID: 8723718 The genetics of cornea plana congenita Tahvanainen, E.; Forsius, H.; Kolehmainen, J.; Damsten, M.; Fellman, J.; de la Chapelle, A. : The genetics of cornea plana congenita. J. Med. Genet. 33: 116-119, 1996. PubMed ID: 8929947 Mutations in KERA, encoding keratocan, cause cornea plana Pellegata, N. S.; Dieguez-Lucena, J. L.; Joensuu, T.; Lau, S.; Montgomery, K. T.; Krahe, R.; Kivela, T.; Kucherlapati, R.; Forsius, H.; de la Chapelle, A. : Mutations in KERA, encoding keratocan, cause cornea plana. Nature Genet. 25: 91-95, 2000. PubMed ID: 10802664 Read more about Cornea Plana
Dominantly and recessively inherited cornea plan congenita map to the same small region of chromosome 12. Tahvanainen, E.; Villanueva, A. S.; Forsius, H.; Salo, P.; de la Chapelle, A. : Dominantly and recessively inherited cornea plana congenita map to the same small region of chromosome 12. Genome Res. 6: 249-254, 1996. PubMed ID: 8723718
The genetics of cornea plana congenita Tahvanainen, E.; Forsius, H.; Kolehmainen, J.; Damsten, M.; Fellman, J.; de la Chapelle, A. : The genetics of cornea plana congenita. J. Med. Genet. 33: 116-119, 1996. PubMed ID: 8929947
Mutations in KERA, encoding keratocan, cause cornea plana Pellegata, N. S.; Dieguez-Lucena, J. L.; Joensuu, T.; Lau, S.; Montgomery, K. T.; Krahe, R.; Kivela, T.; Kucherlapati, R.; Forsius, H.; de la Chapelle, A. : Mutations in KERA, encoding keratocan, cause cornea plana. Nature Genet. 25: 91-95, 2000. PubMed ID: 10802664
