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Isolated congenital megalocornea(MGC1)

MedGen UID:
1385311
Concept ID:
C4518341
Congenital Abnormality
Synonym: MGC1
SNOMED CT: Isolated congenital megalocornea (734026006); Congenital anterior megalophthalmia (734026006)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): CHRDL1 (Xq23)
 
Monarch Initiative: MONDO:0010649
OMIM®: 309300
Orphanet: ORPHA91489

Definition

Isolated congenital megalocornea is a genetic, non-syndromic developmental defect of the anterior eye segment. The disease has characteristics of bilateral enlargement of the corneal diameter and a deep anterior eye chamber, without an elevation in intraocular pressure. It can manifest with mild to moderate myopia as well as photophobia and iridodonesis (due to iris hypoplasia). Associated complications include lens dislocation, retinal detachment, presenile cataract development and secondary glaucoma. There is evidence this disease is caused by mutation in the CHRDL1 gene on chromosome Xq23. [from SNOMEDCT_US]

Clinical features

From HPO
Arcus senilis
MedGen UID:
8179
Concept ID:
C0003742
Finding
A hazy, grayish-white ring about 2 mm in width located close to but separated from the limbus (the corneoscleral junction). Corneal arcus generally occurs bilaterally, and is related to lipid deposition in the cornea. Corneal arcus can occur in elderly persons as a part of the aging process but may be associated with hypercholesterolemia in people under the age of 50 years.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
Lens subluxation
MedGen UID:
9718
Concept ID:
C0023316
Disease or Syndrome
Partial dislocation of the lens of the eye.
Miosis
MedGen UID:
6409
Concept ID:
C0026205
Disease or Syndrome
Abnormal (non-physiological) constriction of the pupil.
Retinal detachment
MedGen UID:
19759
Concept ID:
C0035305
Disease or Syndrome
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Megalocornea
MedGen UID:
138008
Concept ID:
C0344530
Congenital Abnormality
Megalocornea is an inherited eye disorder in which the corneal diameter is bilaterally enlarged (greater than 13 mm) without an increase in intraocular pressure. It may also be referred to as 'anterior megalophthalmos,' since the entire anterior segment is larger than normal. Features of megalocornea in addition to a deep anterior chamber include astigmatic refractive errors, atrophy of the iris stroma, miosis secondary to decreased function of the dilator muscle, iridodonesis, and tremulousness, subluxation, or dislocation of the lens. Whereas most affected individuals exhibit normal ocular function, complications include cataract development and glaucoma following lenticular dislocation or subluxation. X-linked recessive inheritance is the most common pattern, accounting for the male preponderance of the disorder (summary by Skuta et al., 1983). Megalocornea sometimes occurs as part of the Marfan syndrome (154700). Genetic Heterogeneity of Megalocornea Autosomal recessive megalocornea has been reported (249300).
Deep anterior chamber
MedGen UID:
602219
Concept ID:
C0423280
Finding
Increased depth of the anterior chamber, i.e., the anteroposterior distance between the cornea and the iris is increased.
Iridodonesis
MedGen UID:
451052
Concept ID:
C0423320
Disease or Syndrome
Tremulousness of the iris on movement of the eye, occurring in subluxation of the lens.
Abnormal intraocular pressure
MedGen UID:
636377
Concept ID:
C0520999
Finding
An anomaly in the amount of force per unit area exerted by the intraocular fluid within the eye.
Iris transillumination defect
MedGen UID:
786045
Concept ID:
C1096099
Anatomical Abnormality
Transmission of light through the iris as visualized upon slit lamp examination or infrared iris transillumination videography. The light passes through defects in the pigmentation of the iris.
Decreased corneal thickness
MedGen UID:
473349
Concept ID:
C1096274
Finding
A decreased anteroposterior thickness of the cornea.
Mosaic corneal dystrophy
MedGen UID:
870342
Concept ID:
C4024786
Disease or Syndrome

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Weiner C, Hecht I, Kotlyar A, Shoshany N, Zadok D, Elbaz U, Segev F, Maytal A, Hachmo Y, Michiels C, De Backer O, Shomron N, Einan-Lifshitz A, Pras E
JAMA Ophthalmol 2021 Oct 1;139(10):1089-1095. doi: 10.1001/jamaophthalmol.2021.3172. PMID: 34410316Free PMC Article
Edward DP, Morales J, Bouhenni RA, Patil J, Edward PR, Cummings TJ, Chaudhry IA, Alkatan H
Ophthalmology 2012 Jul;119(7):1485-94. Epub 2012 Apr 4 doi: 10.1016/j.ophtha.2012.01.027. PMID: 22480745

Diagnosis

Edward DP, Morales J, Bouhenni RA, Patil J, Edward PR, Cummings TJ, Chaudhry IA, Alkatan H
Ophthalmology 2012 Jul;119(7):1485-94. Epub 2012 Apr 4 doi: 10.1016/j.ophtha.2012.01.027. PMID: 22480745

Prognosis

Edward DP, Morales J, Bouhenni RA, Patil J, Edward PR, Cummings TJ, Chaudhry IA, Alkatan H
Ophthalmology 2012 Jul;119(7):1485-94. Epub 2012 Apr 4 doi: 10.1016/j.ophtha.2012.01.027. PMID: 22480745

Clinical prediction guides

Gutiérrez-Amavizca BE, Juárez-Vázquez CI, Orozco-Castellanos R, Arnaud L, Macías-Gómez NM, Barros-Nuñez P
Genet Couns 2013;24(2):185-91. PMID: 24032289
Edward DP, Morales J, Bouhenni RA, Patil J, Edward PR, Cummings TJ, Chaudhry IA, Alkatan H
Ophthalmology 2012 Jul;119(7):1485-94. Epub 2012 Apr 4 doi: 10.1016/j.ophtha.2012.01.027. PMID: 22480745

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