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Megalocornea
Introduction
Megalocornea, also known as anterior megalophthalmos, X-linked megalocornea, and macrocornea, is a rare bilateral nonprogressive congenital defect that is characterized by an increased corneal diameter greater than 12.5 to 13 mm at birth and a deep anterior chamber with normal intraocular pressures.[1][2] Thinning of the cornea has also been frequently associated.[3] The defect falls under the category of anterior segment dysgenesis and is associated with several other conditions, including Axenfeld-Rieger syndrome, Peters anomaly, primary congenital glaucoma, aniridia, congenital hereditary endothelial dystrophy, and sclerocornea.[2] In addition, it is a component of many different congenital syndromes.
There are two patterns of clinical presentation. Primary megalocornea is an isolated megalocornea with no additional ocular or systemic manifestations. The second clinical presentation is megalocornea with other associated ocular and systemic abnormalities. This article will focus on primary congenital megalocornea (hereafter referred to as megalocornea) and will discuss possible comorbid conditions and syndromes in the ‘differential diagnosis’ section.
Primary megalocornea was first described in 1869, but the genetic basis of this disease has only been elucidated in the past decade.[1][3] The disease is usually inherited in an X-linked fashion, but other inheritance patterns have been described.[4][5] The disease is generally asymptomatic in childhood though astigmatism from the large cornea may result in blurred vision.[4][6] Adults may experience premature cataract formation, typically between the ages of 30 and 50, glaucoma, arcus juvenilis, lens subluxation, and mosaic corneal dystrophy.[4][7][8] Other described comorbidities include iris atrophy, coloboma, abnormalities in zonular fibers, transillumination of the irides, lens dislocation, retinal detachment, and asymmetry in corneal size.[1][4][7][9][10][11][12]
Etiology
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Etiology
Since multiple diseases can present with an enlarged cornea or globe, there are numerous associated causes and potential genetic inheritance patterns. Also, not all studies state whether the patient in question had other genetic abnormalities or if the defect was noted in isolation. X-linked megalocornea has been the most studied and best described in the literature and is most frequently associated with megalocornea. In 1991, the affected gene was noted to be located at the Xq13-q25 region of the X-chromosome[7][10], but due to the large size of that region (about 24.3 Mb), it wasn’t until 2012 that the Chordin-like 1 (CHRDL1) gene was identified as the causative locus.[3] Various mutations in this gene have been observed that give rise to the classic phenotype.[3][6][9][13]
In addition to X-chromosome mutations that can lead to megalocornea, autosomal chromosomes have been associated with the defect as well. Duplications in the 16p chromosomal region have resulted in megalocornea without other congenital or acquired defects.[14]
Epidemiology
Though many published reports describe the condition as “rare,” to our knowledge there are no epidemiologic studies on the incidence or prevalence of megalocornea. Conditions associated with megalocornea may have their own epidemiologic information.
Pathophysiology
CHRDL1 codes for a protein called ventroptin, a bone morphogenic protein (BMP) antagonist which has full penetrance. In the eye, the gene is expressed in the human cornea, lens, and retina as early as gestational week seven, and expression persists into adulthood.[3][9] Also, ventroptin has embryologic functions elsewhere and plays a role in many parts of the body. The absence of ventroptin may lead to BMP excess and unregulated corneal proliferation. Imbalances in the ventroptin to BMP ratio are hypothesized to cause accelerated differentiation and proliferation of limbal stem cells, causing the observed phenotype.[9] This is consistent with the understanding that a decrease in BMP levels can lead to microphthalmia.[15][16] The low levels of BMP may lead to BMP receptor downregulation, the amount of which may explain variation between affected individuals.[9] In addition, the corneal epithelium displays normal morphology and density. Thus, the gene disruption seems to result in total corneal hyperplasia.[17] This normal density of cells in the cornea also supports the theory that megalocornea is the result of the failure of the anterior cup to fuse at the appropriate time, allowing for excess growth in an irregular ratio. The optic cup originates as a bell-shaped structure before becoming more spherical. A delay in this change may allow for a permanent increase in the diameter of the anterior structures of the eye. This overgrowth may be the cause of the lens and iris being positioned more posteriorly in some cases.[18]
History and Physical
Children with megalocornea may not have visual complaints, and cases of missed diagnosis, even in the presence of outpatient ophthalmic care, have been reported. Though a deep anterior chamber is a prominent feature of the disease, the vitreous chamber length is decreased, and the overall axial length remains normal.[4] The iris and the lens are positioned more posteriorly.[18] Wide, open iridocorneal angles are expected, and excessive pigmentation of the trabecular meshwork may be noted.[4] In some cases, corneal optical aberration may be observable with the ability to view angle structures without gonioscopy.[19] Finally, it has been reported that cornea globosa is a pathognomonic characteristic specific to X-linked megalocornea, and biometric findings differ in these patients.[18] In patients with complications from congenital megalocornea (e.g., cataracts, retinal detachment), symptoms will resemble the immediate concern (e.g., blurry vision, glare, flashes or floaters, etc.).
Evaluation
Congenital megalocornea may be asymptomatic for some patients. Thus, the diagnosis may not be made until complications arise.[4] Although ventroptin is associated with retinal development, patients with CHRDL1 associated megalocornea generally have normal fundi and optic discs. Electroretinograms have shown some generalized cone system dysfunction in select patients, and visual evoked potentials may show delays in pathway conduction, which may be explained by a decrease in white matter myelination. However, the patient's cognitive ability remains intact, or slightly above average.[3] Thus, diagnosis in patients with mildly enlarged corneas may be difficult.
Due to the variety of discovered mutations thus far, and the likelihood of additional mutations existing, genetic testing across the entire coding region in the X chromosome is the most definitive diagnostic measure to establish a correct diagnosis and allow for the best possible patient care.[3][6][9]. Other genetic or diagnostic testing may be appropriate if an associated syndrome or condition is suspected.
Treatment / Management
Since the underlying defect is anatomic, there is no cure or treatment for the enlarged corneas seen in megalocornea. Complications as a result of the underlying defect can also be challenging to treat due to abnormal anatomy. For example, a large ciliary ring and capsular bag with normal-sized lens and weak zonular fibers can complicate cataract surgery, the most common intervention in these patients.[20] In such cases, ultrasound biomicroscopy may help determine capsular bag size.[21] Though there is an increase in surgical difficulty, many have been successfully completed. Older literature reports intracapsular lens extraction, with manual extracapsular cataract extraction (ECCE) techniques being reported later. Within the last ten years, there have been multiple reports of phacoemulsification as an effective modality.[22](B3)
Determining the appropriate power of the lens can be difficult since the normal anatomy that is assumed when using third-generation intraocular lens formulas is not present. In deciding on a formula, one that incorporates the anterior chamber depth and corneal curvature should be used as the anterior chamber is generally excessively deep, and the corneal curvature tends to be more divergent in patients with megalocornea (>2 standard deviations). The Holladay II formula has been shown to be superior to SRK-T, though neither remained at the ideal power, and further follow up is needed since lens power may not differ between the two.[22][23][24] Targeting more myopic refraction should, therefore, be encouraged as patients tend to have residual hyperopia[22]. One report indicated that the Haigis formula might be the best choice when choosing an intraocular lens.[25](B3)
Due to the increased size of the structures, standard intraocular lenses may decenter, and iris suturing, scleral fixation, or an iris-claw intraocular lens may be required.[26][27][28] However, 3-piece intraocular lenses have been reported to be effective.[22] Additionally, since wound leakage, guttata, and low endothelial cell counts may be more common in patients with megalocornea, attempts to limit corneal trauma using scleral tunnel incisions with sutures may be suggested for anterior chamber access, and suturing the wound has been suggested to prevent possible postoperative hypotony.[22][28] With these potential complications in mind, a number of possible approaches to cataract surgery in these patients have been reported, each often specific to the patient’s individual needs. However, an iris-claw intraocular lens tends to be the generally recommended treatment option to allow for the best long-term visual outcomes without the need for additional procedures.[21](B3)
Differential Diagnosis
The most commonly encountered differential diagnosis in the infant with megalocornea is infantile glaucoma. On examination, the child with megalocornea will likely have many of the features previously described in this article, most distinguishingly, normal intraocular pressures, a positive family history, and an intact Descemet’s membrane. On the other hand, patients with congenital glaucoma characteristically have elevated intraocular pressures and breaks in Descemet’s membrane and may present with corneal edema. Additionally, features of primary megalocornea such as pigment dispersion and iris transillumination will be absent in patients with infantile glaucoma.[9][11][13] Other ocular enlargements also need to be distinguished from megalocornea. These include keratoglobus and megalophthalmos.[21]
Other syndromes, diseases, or conditions associated with megalocornea are summarized below.
- Neuhäuser syndrome, also known as megalocornea-mental retardation (MMR) syndrome, may present with intellectual disability, seizures, hypotonia, and characteristic facial features.[13]
- Frank-Ter Haar syndrome is an additional condition that affects the eyes, heart, and bones. This autosomal recessive condition is commonly associated with skeletal, facial, and various congenital heart defects.[29][30]
- Buphthalmus, or enlargement of the entire eyeball, may also present with megalocornea. It can be differentiated by the presence of glaucoma and the lack of family history.[31]
- Crouzon syndrome is the premature closure of a cranial suture leading to cranial morphologic defects. It is inherited in an autosomal dominant manner and may present with proptosis and shallow orbits.[32]
- Marfan syndrome, a connective tissue disorder, is the result of a mutation in fibrillin and has been reportedly associated with megalocornea.[33] Other conditions with marfanoid habitus have also been associated with megalocornea.[34]
- Albinism, in some cases, has been associated with megalocornea in addition to other comorbidities.[35][36]
- Ritscher-Schinzel syndrome (also called cranio-cerebello-cardiac dysplasia and 3C syndrome) manifests with various ocular, cardiac, and craniofacial anomalies. Megalocornea has been reported as the most common ocular manifestation.[37]
- Wolfram-like syndrome is an autosomal dominant disease that presents with ocular atrophy, diabetes mellitus, and progressive congenital hearing loss. Various ocular concerns, including megalocornea, are associated.[38]
- Lamellar ichthyosis is generally recognized as a cutaneous disorder, but associated megalocornea has been reported.[39]
- Osteogenesis imperfecta, a collagen-based connective tissue disease, is classically associated with ‘brittle’ bones and may have blue sclera. Megalocornea has been associated in one case.[40]
Prognosis
The prognosis in a patient with megalocornea depends on whether or not there is an associated disease or syndrome that results in additional comorbidities. In cases of primary megalocornea, the prognosis is good, as associated conditions may be corrected either with glasses, medication, or surgical intervention with high success.
Complications
Megalocornea is most often asymptomatic in children, and visual acuity is generally preserved. However, vision may be diminished due to a large cornea resulting in astigmatism. Photorefractive keratectomy has been recommended as a possible fix for these patients.[41] Other complications include presenile cataract formation, which is a complicated ocular procedure due to changes in anatomy. However, success is still likely, and surgical outcomes are good. Glaucoma, arcus juvenilis, lens subluxation, and mosaic corneal dystrophy are also commonly associated complications that may develop.[7]
Deterrence and Patient Education
Congenital megalocornea may be associated with other underlying genetic malformations, and patients, or their parents in the case of infants and young children, should be appropriately advised. As nearly all causes of megalocornea are rare, testing (including genetic testing), may be appropriate for the proper diagnosis. Additionally, providers should limit unnecessary testing where possible. Patients and families should be informed about potential additional ocular effects that may occur later in life, and genetic counseling should be offered in many cases as appropriate.
Pearls and Other Issues
- Primary congenital megalocornea is characterized by enlarged corneas and deep anterior chambers without an increase in intraocular pressure.
- This rare genetic defect has been localized to the chordin-like 1 (CHRDL1) gene, which synthesizes the protein ventroptin, a BMP antagonist expressed in ocular structures early in development.
- This defect is located at the X chromosome, and the disease is generally inherited in an X-linked recessive pattern, though other inheritances have been reported
- Since megalocornea is associated with numerous other genetic syndromes and diseases, a thorough workup should be completed to assess for potential underlying causes.
- Patients may be asymptomatic or have astigmatism at birth. Presenile cataracts, ectopia lentis, and glaucoma may arise and are the most serious complications.
Enhancing Healthcare Team Outcomes
Infants born with megalocornea should be referred to pediatricians or specialists who can appropriately diagnose and treat the underlying syndromes or other associated conditions if present. A pediatric ophthalmologist should be part of the team to assess for congenital or acquired ocular defects with eventual transfer to a general or cornea specialist as the child ages. Anesthesia professionals should also be a part of the team because complete ocular examinations may require sedating infants and very young children. Ophthalmology nurses assist in evaluation, patient education, and follow-up care. Nurses should communicate effectively with treating physicians to coordinate care and enhance patient outcomes. [Level 5]
References
Meire FM. Megalocornea. Clinical and genetic aspects. Documenta ophthalmologica. Advances in ophthalmology. 1994:87(1):1-121 [PubMed PMID: 7835180]
Level 3 (low-level) evidenceIto YA, Walter MA. Genomics and anterior segment dysgenesis: a review. Clinical & experimental ophthalmology. 2014 Jan-Feb:42(1):13-24. doi: 10.1111/ceo.12152. Epub 2013 Jul 29 [PubMed PMID: 24433355]
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. American journal of human genetics. 2012 Feb 10:90(2):247-59. doi: 10.1016/j.ajhg.2011.12.019. Epub 2012 Jan 26 [PubMed PMID: 22284829]
Chlasta-Twardzik E, Nowińska A, Wąs P, Jakubowska A, Wylęgała E. Traumatic cataract in patient with anterior megalophthalmos: Case report. Medicine. 2017 Jul:96(30):e7160. doi: 10.1097/MD.0000000000007160. Epub [PubMed PMID: 28746174]
Level 3 (low-level) evidencePearce WG. Autosomal dominant megalocornea with congenital glaucoma: evidence for germ-line mosaicism. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie. 1991 Feb:26(1):21-6 [PubMed PMID: 2013021]
Level 3 (low-level) evidenceHan J, Young JW, Frausto RF, Isenberg SJ, Aldave AJ. X-linked Megalocornea Associated with the Novel CHRDL1 Gene Mutation p.(Pro56Leu*8). Ophthalmic genetics. 2015 Jun:36(2):145-8. doi: 10.3109/13816810.2013.837187. Epub 2013 Sep 27 [PubMed PMID: 24073597]
Mackey DA, Buttery RG, Wise GM, Denton MJ. Description of X-linked megalocornea with identification of the gene locus. Archives of ophthalmology (Chicago, Ill. : 1960). 1991 Jun:109(6):829-33 [PubMed PMID: 2043071]
Saatci AO, Söylev M, Kavukçu S, Durak I, Saatci I, Memişoğlu B. Bilateral megalocornea with unilateral lens subluxation. Ophthalmic genetics. 1997 Mar:18(1):35-8 [PubMed PMID: 9134548]
Level 3 (low-level) evidencePfirrmann T, Emmerich D, Ruokonen P, Quandt D, Buchen R, Fischer-Zirnsak B, Hecht J, Krawitz P, Meyer P, Klopocki E, Stricker S, Lausch E, Seliger B, Hollemann T, Reinhard T, Auw-Haedrich C, Zabel B, Hoffmann K, Villavicencio-Lorini P. Molecular mechanism of CHRDL1-mediated X-linked megalocornea in humans and in Xenopus model. Human molecular genetics. 2015 Jun 1:24(11):3119-32. doi: 10.1093/hmg/ddv063. Epub 2015 Feb 23 [PubMed PMID: 25712132]
Level 3 (low-level) evidenceMeire FM, Bleeker-Wagemakers EM, Oehler M, Gal A, Delleman JW. X-linked megalocornea. Ocular findings and linkage analysis. Ophthalmic paediatrics and genetics. 1991 Sep:12(3):153-7 [PubMed PMID: 1754164]
Ho CL, Walton DS. Primary megalocornea: clinical features for differentiation from infantile glaucoma. Journal of pediatric ophthalmology and strabismus. 2004 Jan-Feb:41(1):11-7; quiz 46-7 [PubMed PMID: 14974829]
Guixeres Esteve MC, Pardo Saiz AO, Martínez-Costa L, González-Ocampo Dorta S, Sanz Solana P. Surgical Management of a Patient with Anterior Megalophthalmos, Lens Subluxation, and a High Risk of Retinal Detachment. Case reports in ophthalmology. 2017 Jan-Apr:8(1):61-66. doi: 10.1159/000456068. Epub 2017 Jan 26 [PubMed PMID: 28203198]
Level 3 (low-level) evidenceDavidson 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, Neuhäuser syndrome and central corneal thickness. PloS one. 2014:9(8):e104163. doi: 10.1371/journal.pone.0104163. Epub 2014 Aug 5 [PubMed PMID: 25093588]
Samalia P, Buller A. Megalocornea associated with microduplications on chromosome 16. Ophthalmic genetics. 2018 Jan-Feb:39(1):129-130. doi: 10.1080/13816810.2017.1317818. Epub 2017 Apr 28 [PubMed PMID: 28453371]
Bakrania P, Efthymiou M, Klein JC, Salt A, Bunyan DJ, Wyatt A, Ponting CP, Martin A, Williams S, Lindley V, Gilmore J, Restori M, Robson AG, Neveu MM, Holder GE, Collin JR, Robinson DO, Farndon P, Johansen-Berg H, Gerrelli D, Ragge NK. Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. American journal of human genetics. 2008 Feb:82(2):304-19. doi: 10.1016/j.ajhg.2007.09.023. Epub 2008 Jan 31 [PubMed PMID: 18252212]
Level 2 (mid-level) evidenceReis LM, Tyler RC, Schilter KF, Abdul-Rahman O, Innis JW, Kozel BA, Schneider AS, Bardakjian TM, Lose EJ, Martin DM, Broeckel U, Semina EV. BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome. Human genetics. 2011 Oct:130(4):495-504. doi: 10.1007/s00439-011-0968-y. Epub 2011 Feb 22 [PubMed PMID: 21340693]
Level 3 (low-level) evidenceSkuta GL, Sugar J, Ericson ES. Corneal endothelial cell measurements in megalocornea. Archives of ophthalmology (Chicago, Ill. : 1960). 1983 Jan:101(1):51-3 [PubMed PMID: 6849653]
Meire FM, Delleman JW. Biometry in X linked megalocornea: pathognomonic findings. The British journal of ophthalmology. 1994 Oct:78(10):781-5 [PubMed PMID: 7803356]
Yeo DCM, Figg S, Moore W. Direct View of the Angle Structures in Bilateral Congenital Megalocornea. Ophthalmology. 2018 May:125(5):700. doi: 10.1016/j.ophtha.2018.01.008. Epub [PubMed PMID: 29681294]
Sharan S, Billson FA. Anterior megalophthalmos in a family with 3 female siblings. Journal of cataract and refractive surgery. 2005 Jul:31(7):1433-6 [PubMed PMID: 16105619]
Level 3 (low-level) evidenceGalvis V, Tello A, M Rangel C. Cataract Surgery in Anterior Megalophthalmos: A Review. Medical hypothesis, discovery & innovation ophthalmology journal. 2015 Fall:4(3):101-8 [PubMed PMID: 27350950]
Assia EI, Segev F, Michaeli A. Cataract surgery in megalocornea Comparison of 2 surgical approaches in a single patient. Journal of cataract and refractive surgery. 2009 Dec:35(12):2042-6. doi: 10.1016/j.jcrs.2009.06.043. Epub [PubMed PMID: 19969205]
Level 3 (low-level) evidenceDe la Parra-Colín P, Barrientos-Gutierrez T, Mian SI. Axial length's role in intraocular lens power calculation error in X-linked megalocornea: a case-series analysis. Ophthalmic genetics. 2014 Sep:35(3):180-3. doi: 10.3109/13816810.2013.804099. Epub 2013 Sep 3 [PubMed PMID: 24001017]
Level 3 (low-level) evidencede Sanctis U, Grignolo FM. Cataract extraction in X-linked megalocornea: a case report. Cornea. 2004 Jul:23(5):533-5 [PubMed PMID: 15220744]
Level 3 (low-level) evidenceMiao A, Zhang K, Yu J, He W, Lu Y, Zhu X. How many challenges we may encounter in anterior megalophthalmos with white cataract: a case report. BMC ophthalmology. 2019 May 30:19(1):122. doi: 10.1186/s12886-019-1133-y. Epub 2019 May 30 [PubMed PMID: 31146719]
Level 3 (low-level) evidenceMessina M, Ross AR, Pocobelli G, Said DG, Dua HS. Cataract surgery with intraocular lens implantation in 3 brothers with megalocornea: Long-term follow-up. Journal of cataract and refractive surgery. 2018 Mar:44(3):399-402. doi: 10.1016/j.jcrs.2018.01.020. Epub [PubMed PMID: 29703292]
Galvis V, Tello A, Rangel CM, Carreño NI, Berrospi RD, Niño CA. Iris-clip versus iris-claw intraocular lenses. Journal of cataract and refractive surgery. 2018 Nov:44(11):1407. doi: 10.1016/j.jcrs.2018.08.007. Epub [PubMed PMID: 30368364]
Sati A, Murthy SI, Arjun S, Rathi VM. Anterior megalophthalmos: Is visual restoration possible? Oman journal of ophthalmology. 2018 May-Aug:11(2):184-186. doi: 10.4103/ojo.OJO_165_2015. Epub [PubMed PMID: 29930460]
Chang TC, Bauer M, Puerta HS, Greenberg MB, Cavuoto KM. Ophthalmic findings in Frank-ter Haar syndrome: report of a sibling pair. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus. 2017 Dec:21(6):514-516. doi: 10.1016/j.jaapos.2017.07.216. Epub 2017 Oct 31 [PubMed PMID: 29100834]
Saeed M, Shair QA, Saleem SM. Frank-Ter Haar Syndrome. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2011 Apr:21(4):252-3 [PubMed PMID: 21453629]
Level 3 (low-level) evidencePletz C, Hentsch R. [Hereditary anterior megalophthalmus--a genealogical study of 12 patients in 4 generations]. Klinische Monatsblatter fur Augenheilkunde. 2000 Nov:217(5):284-8 [PubMed PMID: 11146827]
Level 3 (low-level) evidenceAlshamrani AA, Al-Shahwan S. Glaucoma With Crouzon Syndrome. Journal of glaucoma. 2018 Jun:27(6):e110-e112. doi: 10.1097/IJG.0000000000000946. Epub [PubMed PMID: 29557836]
Consul BN,Mehrotra AS,Mathur GB, Marfan's syndrome with bilateral megalocornea and subluxated cataractous lenses. Journal of the All-India Ophthalmological Society. 1966 Dec; [PubMed PMID: 5990447]
Morlino S, Alesi V, Calì F, Lepri FR, Secinaro A, Grammatico P, Novelli A, Drago F, Castori M, Baban A. LTBP2-related "Marfan-like" phenotype in two Roma/Gypsy subjects with the LTBP2 homozygous p.R299X variant. American journal of medical genetics. Part A. 2019 Jan:179(1):104-112. doi: 10.1002/ajmg.a.10. Epub 2018 Dec 18 [PubMed PMID: 30565850]
Dubé P, Der Kaloustian VM, Demczuk S, Saabti H, Koenekoop RK. A new association of congenital hydrocephalus, albinism, megalocornea, and retinal coloboma in a syndromic child: a clinical and genetic study. Ophthalmic genetics. 2000 Dec:21(4):211-6 [PubMed PMID: 11135491]
Level 3 (low-level) evidenceShiono T, Tsunoda M, Chida Y, Nakazawa M, Tamai M. X linked ocular albinism in Japanese patients. The British journal of ophthalmology. 1995 Feb:79(2):139-43 [PubMed PMID: 7696233]
Pira-Paredes SM, Montoya-Villada JH, Franco-Restrepo JL, Moncada-Velez M, Cornejo JW. [A phenotypic description of 26 patients with Ritscher-Schinzel syndrome (cranio-cerebello-cardiac dysplasia or 3C syndrome)]. Revista de neurologia. 2017 Jun 1:64(11):481-488 [PubMed PMID: 28555453]
Prochazkova D, Hruba Z, Konecna P, Skotakova J, Fajkusova L. A p.(Glu809Lys) Mutation in the WFS1 Gene Associated with Wolfram-like Syndrome: A Case Report. Journal of clinical research in pediatric endocrinology. 2016 Dec 1:8(4):482-483. doi: 10.4274/jcrpe.3021. Epub 2016 May 23 [PubMed PMID: 27217304]
Level 3 (low-level) evidenceMansour AM, Traboulsi EI, Frangieh GT, Jarudi N. Unilateral megalocornea in lamellar ichthyosis. Annals of ophthalmology. 1985 Aug:17(8):466-8, 470 [PubMed PMID: 4051379]
Level 3 (low-level) evidenceBohnsack BL. Infantile-onset glaucoma and anterior megalophthalmos in osteogenesis imperfecta. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus. 2016 Apr:20(2):170-2. doi: 10.1016/j.jaapos.2015.11.005. Epub 2016 Mar 16 [PubMed PMID: 26994503]
Gallyas E, Hidasi V, Ferincz I, Kolozsvári L. Photorefractive keratectomy in megalophthalmos anterior. Journal of refractive surgery (Thorofare, N.J. : 1995). 2006 Apr:22(4):408-11 [PubMed PMID: 16629077]
Level 3 (low-level) evidence