X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15.

X-linked cone-rod dystrophy (COD1) is a retinal disease that primarily affects the cone photoreceptors; the disease was originally mapped to a limited region of Xp11.4. We evaluated the three families from our original study with new markers and clinically reassessed all key recombinants; we determined that the critical intervals in families 2 and 3 overlapped the RP3 locus and that a status change (from affected to probably unaffected) of a key recombinant individual in family 1 also reassigned the disease locus to include RP3 as well.

Update on the molecular genetics of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of retinal dystrophies characterized by photoreceptor cell degeneration. RP causes night blindness, a gradual loss of peripheral visual fields, and eventual loss of central vision. Advances in molecular genetics have provided new insights into the genes responsible and the pathogenic mechanisms of RP.

Dominant radial drusen and Arg345Trp EFEMP1 mutation.

Purpose: To report a new North American family with dominant radial drusen and Arg345Trp mutation in the EFEMP1 gene.

Methods: Clinical and molecular genetic family study.

Results: Four family members had macular drusen, and one had submacular fibrosis and visual loss.

Confirmation of the autosomal recessive syndrome of ectopia lentis and distinctive craniofacial appearance.

We report four members of a Lebanese Druze family with the syndrome of lens dislocation, spontaneous filtering blebs, anterior segment abnormalities, and a distinctive facial appearance. The constellation of clinical abnormalities in these patients is not suggestive of the Marfan syndrome or other connective tissue disorders associated with ectopia lentis. We previously described this syndrome in another presumably unrelated and highly inbred Druze family from the mountains of Lebanon.

Anterior transposition of the inferior oblique muscle as the initial treatment of a snapped inferior rectus muscle.

Snapping or tearing of an extraocular muscle refers to its rupture across its width, usually at the junction between muscle and tendon several millimeters behind the insertion. Tearing occurs during strabismus or retinal reattachment surgery, or after trauma. If the proximal end of the muscle cannot be located, transposition procedures are necessary to achieve ocular realignment.

Comparison of clinical characteristics of familial and sporadic acquired accommodative esotropia.

Purpose: To compare the clinical characteristics of patients with familial and nonfamilial acquired accommodative esotropia.

Methods: We recruited 48 patients from 33 families with acquired accommodative esotropia (an inward deviation of the eyes of 10 PD or more, a hypermetropia greater than or equal to +1.50 D, and an onset of esotropia at, or later than, 1 year of age).

Oral erythromycin treatment for childhood blepharokeratitis.

Blepharokeratitis is a chronic external ocular and adnexal inflammatory condition marked by erythematous and edematous lid margins, lid margin crusting and scaling, meibomian gland inflammation and inspissation, and conjunctival hyperemia. The associated keratitis usually involves the inferior cornea and is characterized by punctate epithelial keratopathy and marginal stromal infiltrates. The inflammation sometimes leads to corneal thinning, scarring, and vascularization.

Mutational analysis and clinical correlation in Leber congenital amaurosis.

Unlabelled: Leber congenital amaurosis (LCA, MIM 204001) is a clinically and genetically heterogeneous retinal disorder characterized by severe visual loss from birth, nystagmus, poor pupillary reflexes, retinal pigmentary or atrophic changes, and a markedly diminished electroretinogram (ERG).

Purpose: To examine 100 consecutive patients with LCA in order to assess the relative burden of the three known genes involved in LCA, namely retinal guanylyl cyclase (GUCY2D), retinal pigment epithelium protein ( RPE65), and the cone-rod homeobox (CRX), and to define their clinical correlates.

Methods: Mutational analysis and detailed clinical examinations were performed in patients diagnosed with LCA at the Johns Hopkins Center for Hereditary Eye Diseases and the Montreal Children's Hospital.

Clinical spectrum of chromosome 6-linked autosomal dominant drusen and macular degeneration.

Purpose: To describe the clinical phenotype and the intrafamilial variation in retinal findings in a North American family with an autosomal dominant drusen disorder that maps to chromosome 6q14.

Methods: Ophthalmic examinations were carried out on participating family members. Fundus photographs were obtained whenever possible.

A new locus for dominant drusen and macular degeneration maps to chromosome 6q14.

Purpose: To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family.

Methods: Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration.

Results: The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients.

A patient with de Morsier and Duane syndromes.

de Morsier syndrome, or septo-optic dysplasia, is a developmental malformation complex characterized by optic nerve hypoplasia, dysgenesis of the septum pellucidum, and hypothalamic-pituitary dysfunction. (1,2) In Duane retraction syndrome, there is absence of the sixth nerve nucleus with congenital retraction of the globe and narrowing of the lid fissure in adduction, frequent abduction deficiency, and variable limitation to adduction of the affected eye. (3) The purpose of this report is to present a patient with the uncommon and previously unreported concurrence of both of these congenital malformation complexes, presumably because of a common disturbance of neuronal development.

Human microphthalmia associated with mutations in the retinal homeobox gene CHX10.

Isolated human microphthalmia/anophthalmia, a cause of congenital blindness, is a clinically and genetically heterogeneous developmental disorder characterized by a small eye and other ocular abnormalities. Three microphthalmia/anophthalmia loci have been identified, and two others have been inferred by the co-segregation of translocations with the phenotype. We previously found that mice with ocular retardation (the or-J allele), a microphthalmia phenotype, have a null mutation in the retinal homeobox gene Chx10 (refs 7,8).

Choroidal rupture associated with forceps delivery.

Purpose: To report a case of choroidal rupture associated with forceps delivery.

Method: Case report.

Results: We examined a 4-year-old boy with a history of a retinal scar in the right eye.

Screening relatives of patients with familial chronic open angle glaucoma.

Purpose: To describe the value and the results of screening of family members of individuals with familial chronic open-angle glaucoma (COAG) for the disease.

Design: Cross-sectional study of families with COAG.

Participants: Eighty-six individuals from 15 families with COAG.

Evidence of genetic heterogeneity in autosomal recessive congenital fibrosis of the extraocular muscles.

Purpose: Autosomal recessive congenital fibrosis of the extraocular muscles (CFEOM2) has been described in families from Saudi Arabia. Affected individuals have ptosis and exotropic ophthalmoplegia, and their disease has been mapped to chromosome 11q13. Here, we describe the phenotypic findings in a similarly affected Yemenite family and analyze the family for linkage to the CFEOM2 locus, as well as to the autosomal dominant CFEOM1 and CFEOM3 loci on chromosomes 12cen and 16q24, respectively.

Morning glory disk anomaly, choroidal coloboma, and congenital constrictive malformations of the internal carotid arteries (moyamoya disease).

Purpose: To report a patient with congenital constrictive malformations of the internal carotid arteries and a morning glory disc anomaly (MGDA).

Methods: Descriptive case report.

Results: A 14-year-old girl underwent serial ophthalmologic examinations since the age of seven years because of blurred vision and floaters.

Microfibril abnormalities of the lens capsule in patients with Marfan syndrome and ectopia lentis.

Purpose: To determine the distribution and structure of fibrillin microfibrils in the three fibrillin-rich lens capsule zones of subjects with the Marfan syndrome.

Methods: Capsules were dissected from nine lenses extracted intracapsularly from Marfan syndrome patients. The capsules were divided and mounted flat on gelatin-coated glass slides.

Posterior scleral choristoma in the organoid nevus syndrome (linear nevus sebaceus of Jadassohn).

Purpose: To highlight the association of posterior osseous and/or cartilaginous ocular choristomas with epibulbar choristomas and the nevus sebaceus of Jadassohn.

Design: Small case series.

Participants: Four patients with the organoid nevus syndrome.

Ocular malformations and developmental genes.

New insights into the pathogenesis of ocular malformations came with the discovery of transcription factors that determine the fate of cells in the developing eye. Several malformations have been matched to individual developmental genes that share conserved DNA sequences such as the homeobox. These disease/gene matches include the oculorenal syndrome and PAX2; aniridia and PAX6; Rieger syndrome and RIEG1/PITX2; cyclopia and Sonic hedgehog; cone-rod dystrophy, Leber's congenital amaurosis and CRX; and recessive septooptic dysplasia and HESX1.

Microcephaly, colobomatous microphthalmia, short stature, and severe psychomotor retardation in two male cousins: a new MCA/MR syndrome?

We report on 2 male cousins with minor facial anomalies, microcephaly, colobomatous microphthalmia, psychomotor retardation, short stature, and skeletal malformations. The children belong to a highly inbred family. We conclude that these patients have a previously undescribed autosomal-recessive syndrome.

Ocular malformations, moyamoya disease, and midline cranial defects: a distinct syndrome.

Purpose: To report a 10-year-old girl with developmental anomalies of both optic disks, a chorioretinal coloboma, sphenopharyngeal meningoencephalocele, and moyamoya disease.

Methods: A full ophthalmologic examination, cranial magnetic resonance imaging and magnetic resonance angiography, and cerebral angiography were performed.

Results: The patient had a morning glory disk anomaly and microphthalmos of the right eye and optic nerve hypoplasia and retinochoroidal coloboma in the left eye.

Coloboma of the lens, optic nerve hypoplasia, and orbital hemangioma--a possible developmental field defect.

Purpose: To report the unusual association of a coloboma of the lens with ipsilateral optic nerve hypoplasia and orbital hemangioma.

Methods: Descriptive case report.

Results: An eight-month-old girl had a gradually enlarging left orbital hemangioma.