iridodenesis

Anterior Segment Dysgenesis 6

Clinical Characteristics
Ocular Features: 

This is a congenital anterior segment dysplasia syndrome.  Iris hypoplasia with transillumination, corectopia, iridodenesis, and iridocorneal adhesions can be seen.  Increased intraocular pressure is a risk and ectopia lentis is often present.  Peters anomaly and defects in all layers of the cornea may be present.

No foveal hypoplasia is present.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

A single male patient of native American/French Canadian background has been reported with compound heterozygous mutations in the CYP1B1 gene (2p22.2).

See Anterior Chamber Dysgenesis 8 for another autosomal recessive disorder with somewhat similar clinical features.  Three families with 4 affected individuals have been reported with homozygous or compound heterozygous mutations in the CPAMD8 gene (19p13.11).

The genes FOXE3 and PAX6 are characterized as transcription factors and play important roles in ocular development.  However, while mutations in these are frequently found in patients with dysgenesis of the anterior chamber they often cause more widespread ocular and systemic anomalies (e.g., Gillespie syndrome [206700]).  Therefore in this database the anterior chamber constellations of anomalies associated with mutations in these genes are not considered to be simplex conditions.

See also related disorders iridogoniodysgenesis type 1 (601631) and type 2 (137600), and anterior segment mesenchymal dysgenesis (107250).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Lifelong pressure monitoring is important.

References
Article Title: 

Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly

Vincent A, Billingsley G, Priston M, Williams-Lyn D, Sutherland J, Glaser T, Oliver E, Walter MA, Heathcote G, Levin A, Heon E. Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly. J Med Genet. 2001 May;38(5):324-6. PubMed PMID: 11403040; PubMed Central PMCID: PMC1734880.

PubMed ID: 
11403040

Anterior Segment Dysgenesis 8

Clinical Characteristics
Ocular Features: 

This is a congenital anterior segment dysplasia syndrome with considerable clinical heterogeneity.  Iris hypoplasia with transillumination, corectopia, iridodenesis, and iridocorneal adhesions are often seen.  Intraocular pressure may be elevated in older individuals.  Ectopia lentis is often present.  Lenticular opacities consisting primarily of posterior cortical opacification are common.  Visual acuity varies from 6/6 to 6/24.

No foveal hypoplasia is present but one of four reported patients was described with bilateral optic nerve dysplasia.     

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

Three families with 4 affected individuals with similar clinical features have been reported with homozygous or compound heterozygous mutations in the CPAMD8 gene (19p13.11).

A single male patient of native American/French Canadian background with somewhat similar clinical features has been reported with compound heterozygous mutations in the CYP1B1 gene (2p22.2) but this is likely a unique condition (Anterior Segment Dysgenesis 6).

The genes FOXE3 and PAX6 are characterized as transcription factors and play important roles in ocular development.  However, while mutations in these are frequently found in patients with dysgenesis of the anterior chamber they often cause more widespread ocular and systemic anomalies (e.g., Gillespie syndrome [206700]).  Therefore in this database the anterior chamber constellations of anomalies associated with mutations in these genes are not considered to be simplex conditions. 

See also related disorders iridogoniodysgenesis type 1 (601631) and type 2 (137600), and anterior segment mesenchymal dysgenesis (107250).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Several patients have had cataract surgery.  Monitoring intraocular pressure throughout life is necessary and prompt treatment for glaucoma is important.

References
Article Title: 

Ectopia lentis, Isolated AD

Clinical Characteristics
Ocular Features: 

Ectopia lentis as an isolated finding has been known for many years although early reports did not rule out features of the Marfan syndrome (154700).  In more recent reports clinical evidence of the Marfan syndrome has been absent in a number of families and there seems little doubt that mutations in the FBN1 can be responsible for isolated ectopia lentis.  Iridodenesis may be noted at birth but the dislocated lens may not be diagnosed until late adulthood in mild cases.  Vision can be normal but nystagmus and strabismus have been noted in other patients. The lenses may be dislocated superiorly and may contain opacities.  Areas of missing zonules have been observed in some patients while others have posterior synechiae.

Systemic Features: 

Related family members have been observed to have polydactyly and craniosynostosis but without dislocated lenses.  It is important to rule out skeletal and cardiac manifestations of the Marfan syndrome because of the prognostic implications.

Genetics

This is an autosomal dominant disorder attributed to mutations in FBN1 (15q21), the same gene that is mutant in the Marfan syndrome (154700).  The dislocated lenses may represent variable expressivity or simply allelism.  The latter seems more likely in view of the fact that numerous thoroughly studied individuals have not had the skeletal or cardiovascular signs of the Marfan syndrome (154700).  However, the revised Ghent nosology now suggests that all patients with the FBN1 mutation and ectopia lentis be designated to have the Marfan syndrome when aortic dilation/dissection is present as well.  This should be extended to include all patients with FBN1 mutations and ectopia lentis plus at least one other phenotypic feature of the Marfan syndrome.

The same gene is mutant in the autosomal dominant form of the Weill-Marchesani 2 syndrome (608328) which is allelic to the Marfan syndrome. 

There is also an autosomal recessive condition of isolated ectopia lentis (225100) which results from homozygous nonsense mutations in ADAMTSL4 (225100). A patient with craniosynostosis and ectopia lentis has been reported in which there was a homozygous 20 bp deletion in the same gene.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Lens removal may be indicated when vision cannot otherwise be corrected.

References
Article Title: 

The Revised Ghent Nosology; Reclassifying Isolated Ectopia Lentis

Chandra A, Patel D, Aragon-Martin JA, Pinard A, Collod-Beroud G, Comeglio P, Boileau C, Faivre L, Charteris D, Child AH, Arno G. The Revised Ghent Nosology; Reclassifying Isolated Ectopia Lentis. Clin Genet. 2014 Feb 7. [Epub ahead of print].

PubMed ID: 
24635535

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion

Faivre L, Collod-Beroud G, Callewaert B, Child A, Loeys BL, Binquet C, Gautier E, Arbustini E, Mayer K, Arslan-Kirchner M, Kiotsekoglou A, Comeglio P, Grasso M, Beroud C, Bonithon-Kopp C, Claustres M, Stheneur C, Bouchot O, Wolf JE, Robinson PN, Ades L, De Backer J, Coucke P, Francke U, De Paepe A, Boileau C, Jondeau G. Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion. Am J Med Genet A. 2009 May;149A(5):854-60.

PubMed ID: 
19353630

Ectopia lentis phenotypes and the FBN1 gene

Ades LC, Holman KJ, Brett MS, Edwards MJ, Bennetts B. Ectopia lentis phenotypes and the FBN1 gene. Am J Med Genet A. 2004 Apr 30;126A(3):284-9. Review.

PubMed ID: 
15054843

Ectopia lentis, Isolated AR

Clinical Characteristics
Ocular Features: 

Most dislocated lenses of non-traumatic origin are associated with syndromes, particularly those with defective connective tissue.  However, a few families with dislocated lenses have been reported in which no evidence of defective collagen is present.  The lens is most commonly displaced temporally, often creating myopic astigmatism.  The mean age of discovery of the dislocated lenses is about 2 years of age.  The eye is otherwise normally formed, intraocular pressure is normal, and the axial length is in the normal range.  The cornea, pupil, and iris are normal unlike that found in many patients with ectopia lentis et pupillae (225200).

Systemic Features: 

None by definition.

Genetics

Homozygous nonsense mutations in ADAMTSL4 (1q21.3) are responsible for this autosomal recessive condition.  The same gene is mutated in ectopia lentis et pupillae (225200).  A patient has been reported with craniosynostosis and ectopia lentis in which there was a homozygous 20 bp deletion in this gene.

An autosomal dominant condition of isolated dislocated lenses (129600) secondary to a mutation in FBN1 has also been reported.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Lens removal may be indicated when vision cannot otherwise be corrected.

References
Article Title: 
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