Anterior Segment Dysgenesis 6 Clinical CharacteristicsOcular 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. GeneticsA 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 recessiveTreatmentTreatment Options: Lifelong pressure monitoring is important. ReferencesArticle Title: Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis Cheong SS, Hentschel L, Davidson AE, Gerrelli D, Davie R, Rizzo R, Pontikos N, Plagnol V, Moore AT, Sowden JC, Michaelides M, Snead M, Tuft SJ, Hardcastle AJ. Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis. Am J Hum Genet. 2016 Dec 1;99(6):1338-1352. PubMed ID: 27839872 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 Read more about Anterior Segment Dysgenesis 6
Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis Cheong SS, Hentschel L, Davidson AE, Gerrelli D, Davie R, Rizzo R, Pontikos N, Plagnol V, Moore AT, Sowden JC, Michaelides M, Snead M, Tuft SJ, Hardcastle AJ. Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis. Am J Hum Genet. 2016 Dec 1;99(6):1338-1352. PubMed ID: 27839872
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 CharacteristicsOcular 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. GeneticsThree 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 recessiveTreatmentTreatment Options: Several patients have had cataract surgery. Monitoring intraocular pressure throughout life is necessary and prompt treatment for glaucoma is important. ReferencesArticle Title: Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis Cheong SS, Hentschel L, Davidson AE, Gerrelli D, Davie R, Rizzo R, Pontikos N, Plagnol V, Moore AT, Sowden JC, Michaelides M, Snead M, Tuft SJ, Hardcastle AJ. Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis. Am J Hum Genet. 2016 Dec 1;99(6):1338-1352. PubMed ID: 27839872 Read more about Anterior Segment Dysgenesis 8
Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis Cheong SS, Hentschel L, Davidson AE, Gerrelli D, Davie R, Rizzo R, Pontikos N, Plagnol V, Moore AT, Sowden JC, Michaelides M, Snead M, Tuft SJ, Hardcastle AJ. Mutations in CPAMD8 Cause a Unique Form of Autosomal-Recessive Anterior Segment Dysgenesis. Am J Hum Genet. 2016 Dec 1;99(6):1338-1352. PubMed ID: 27839872
Ectopia Lentis et Pupillae Clinical CharacteristicsOcular Features: This disorder is generally considered to consist of simple displacement of the pupil and dislocation of the lens (usually in opposite directions). However, other abnormalities are often present such as persistent pupillary membrane (87%), iridohyaloid adhesions, increased corneal thickness, enlarged corneal diameters, and axial myopia. The iris may transilluminate (67%) and the pupils dilate poorly. Iridodenesis is common (85%). The lens is often malformed and in some cases frankly microspherophakic. The lens displacement can progress and cataracts seem to form at a relatively young age. Visual acuity is highly variable, ranging from 20/20 to light perception depending upon the density of cataracts which often develop at a relatively young age. Prominent iris processes into the anterior chamber angle have been reported and glaucoma, both acute and chronic, is sometimes seen. Retinal detachment is a risk. Studies in families with ectopia lentis et papillae have revealed that as many as 50% of individuals with dislocated lenses do not have ectopic pupils. Systemic Features: None reported GeneticsThis disorder is usually inherited in an autosomal recessive pattern. Multiple affected sibs have been born to consanquineous matings. However, other families in which detailed ophthalmological examinations were done have suggested dominant inheritance based upon the presence of more subtle ocular signs in relatives. This is likely a more clinically heterogeneous disorder than has been appreciated. In five Norwegian families a homozygous 20 bp deletion has been found in the gene ADAMTSL4 on chromosome 1 (c.767_786del20) (1q21.3) producing a frameshift and the introduction of a stop codon leading to truncation of the protein product. Mutations in the same gene have also been found in the autosomal recessive form of isolated ectopia lentis (225100). Pedigree: Autosomal recessiveTreatmentTreatment Options: Glaucoma, retinal detachments, and cataracts may require surgery. ReferencesArticle Title: A novel ADAMTSL4 mutation in autosomal recessive ectopia lentis et pupillae Christensen AE, Fiskerstrand T, Knappskog PM, Boman H, Rodahl E. A novel ADAMTSL4 mutation in autosomal recessive ectopia lentis et pupillae. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6369-73. PubMed ID: 20702823 Ectopia lentis et pupillae syndrome in three generations Cruysberg JR, Pinckers A. Ectopia lentis et pupillae syndrome in three generations. Br J Ophthalmol. 1995 Feb;79(2):135-8. Review. PubMed ID: 7696232 Clinical manifestations of ectopia lentis et pupillae in 16 patients Goldberg MF. Clinical manifestations of ectopia lentis et pupillae in 16 patients. Ophthalmology. 1988 Aug;95(8):1080-7. PubMed ID: 3266004 Ectopia lentis et pupillae Cross HE. Ectopia lentis et pupillae. Am J Ophthalmol. 1979 Sep;88(3 Pt 1):381-4. PubMed ID: 314755 Read more about Ectopia Lentis et Pupillae
A novel ADAMTSL4 mutation in autosomal recessive ectopia lentis et pupillae Christensen AE, Fiskerstrand T, Knappskog PM, Boman H, Rodahl E. A novel ADAMTSL4 mutation in autosomal recessive ectopia lentis et pupillae. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6369-73. PubMed ID: 20702823
Ectopia lentis et pupillae syndrome in three generations Cruysberg JR, Pinckers A. Ectopia lentis et pupillae syndrome in three generations. Br J Ophthalmol. 1995 Feb;79(2):135-8. Review. PubMed ID: 7696232
Clinical manifestations of ectopia lentis et pupillae in 16 patients Goldberg MF. Clinical manifestations of ectopia lentis et pupillae in 16 patients. Ophthalmology. 1988 Aug;95(8):1080-7. PubMed ID: 3266004
Ectopia lentis et pupillae Cross HE. Ectopia lentis et pupillae. Am J Ophthalmol. 1979 Sep;88(3 Pt 1):381-4. PubMed ID: 314755
