Anterior Segment, Brain, and Facial Anomalies Clinical CharacteristicsOcular Features: The interpupillary distance appears abnormally wide. VEP and ERG responses suggest abnormal retinal bipolar cells. Specular microscopy reveals variable sizes and shapes of corneal endothelial cells with scattered vesicles and large 'holes' in the usual hexagonal array. The iris may be malformed (no collarette, stromal hypoplasia) and there may be peripheral iridocorneal adhesions. Elevated IOP, band keratopathy, corneal clouding, and keratoconus have been reported. Visual acuity is impaired to some extent, from near normal (20/25) to NLP. Progressive optic atrophy was observed in one patient. Systemic Features: Four members of a 3 generation family had malformed pinnae (posterior placement and rotation). Other features variably present were an empty sella turcica, posterior fossa cyst, and hydrocephalus. The propositus also was found to have abnormal auditory bipolar cells based on the audiogram and audio-evoked brainstem responses. GeneticsBased on direct sequencing in one family (3 adults and 1 child), this condition seems to be caused by heterozygous variations or mutations in the VSX1 gene (20p11.21). Pedigree: Autosomal dominantTreatmentTreatment Options: Monitoring for glaucoma and appropriate treatment are indicated. Hearing tests should be performed early. The usual treatments for keratoconus should be considered. Excess brain fluid may need surgical drainage. . ReferencesArticle Title: VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells Mintz-Hittner HA, Semina EV, Frishman LJ, Prager TC, Murray JC. VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells. Ophthalmology. 2004 Apr;111(4):828-36. PubMed ID: 15051220 Read more about Anterior Segment, Brain, and Facial Anomalies
VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells Mintz-Hittner HA, Semina EV, Frishman LJ, Prager TC, Murray JC. VSX1 (RINX) mutation with craniofacial anomalies, empty sella, corneal endothelial changes, and abnormal retinal and auditory bipolar cells. Ophthalmology. 2004 Apr;111(4):828-36. PubMed ID: 15051220
Corneal Dystrophy, Posterior Amorphous Clinical CharacteristicsOcular Features: The iris abnormalities consisting of iridocorneal adhesions to Schwalbe's line and pupillary abnormalities suggest that PACD is a congenital disorder, perhaps a form of anterior chamber dysgenesis. The corneal stroma and Descemet membrane contain sheet-like opacities with clear intervening areas. These opacities are concentrated in the posterior stroma and are sometimes seen from limbus to limbus whereas in other cases they occur mostly peripherally. The cornea may be thinner than normal and somewhat flattened. There is little or no progression of the corneal opacification and vision varies widely. Glaucoma has not been reported. Histological and EM studies have revealed some fracturing and disorganization of the posterior stromal lamellae and focal attenuation of the endothelium. Systemic Features: There is no associated systemic disease. GeneticsA limited number of families with this disorder have been reported and the pattern in each is generally consistent with autosomal dominant inheritance. This may be a deletion syndrome based on the finding in a 1 year old African male with a heterozygous de novo deletion at 12q21.33-q22 containing 11 genes. Anong the missing genes are those for the 4 small leucine-rich proteoglycans associated with this form of corneal dystrophy. The parents did not have the deletion though. Pedigree: Autosomal dominantTreatmentTreatment Options: Treatment is generally not required but penetrating keratoplasty can benefit those whose vision is significantly impaired. ReferencesArticle Title: Posterior amorphous corneal dystrophy caused by a de novo deletion Odent S, Casteels I, Cassiman C, Dieltiens M, Hua MT, Devriendt K. Posterior amorphous corneal dystrophy caused by a de novo deletion. Ophthalmic Genet. 2017 Mar-Apr;38(2):167-170. PubMed ID: 27096414 Posterior amorphous corneal dystrophy. A new pedigree with phenotypic variation Moshegov CN, Hoe WK, Wiffen SJ, Daya SM. Posterior amorphous corneal dystrophy. A new pedigree with phenotypic variation. Ophthalmology. 1996 Mar;103(3):474-8. PubMed ID: 8600425 The pathology of posterior amorphous corneal dystrophy Johnson AT, Folberg R, Vrabec MP, Florakis GJ, Stone EM, Krachmer JH. The pathology of posterior amorphous corneal dystrophy. Ophthalmology. 1990 Jan;97(1):104-9. PubMed ID: 2314832 New findings in posterior amorphous corneal dystrophy Dunn SP, Krachmer JH, Ching SS. New findings in posterior amorphous corneal dystrophy. Arch Ophthalmol. 1984 Feb;102(2):236-9. PubMed ID: 6607727 Posterior amorphous corneal dystrophy Carpel EF, Sigelman RJ, Doughman DJ. Posterior amorphous corneal dystrophy. Am J Ophthalmol. 1977 May;83(5):629-32. PubMed ID: 301356 Read more about Corneal Dystrophy, Posterior Amorphous
Posterior amorphous corneal dystrophy caused by a de novo deletion Odent S, Casteels I, Cassiman C, Dieltiens M, Hua MT, Devriendt K. Posterior amorphous corneal dystrophy caused by a de novo deletion. Ophthalmic Genet. 2017 Mar-Apr;38(2):167-170. PubMed ID: 27096414
Posterior amorphous corneal dystrophy. A new pedigree with phenotypic variation Moshegov CN, Hoe WK, Wiffen SJ, Daya SM. Posterior amorphous corneal dystrophy. A new pedigree with phenotypic variation. Ophthalmology. 1996 Mar;103(3):474-8. PubMed ID: 8600425
The pathology of posterior amorphous corneal dystrophy Johnson AT, Folberg R, Vrabec MP, Florakis GJ, Stone EM, Krachmer JH. The pathology of posterior amorphous corneal dystrophy. Ophthalmology. 1990 Jan;97(1):104-9. PubMed ID: 2314832
New findings in posterior amorphous corneal dystrophy Dunn SP, Krachmer JH, Ching SS. New findings in posterior amorphous corneal dystrophy. Arch Ophthalmol. 1984 Feb;102(2):236-9. PubMed ID: 6607727
Posterior amorphous corneal dystrophy Carpel EF, Sigelman RJ, Doughman DJ. Posterior amorphous corneal dystrophy. Am J Ophthalmol. 1977 May;83(5):629-32. PubMed ID: 301356