Pediatric Ophthalmology
Edited by P. F. Gallin
Thieme Medical Publishers, Inc.
New York ©2000
8
Ocular Genetics
As the prevalence of communicable diseases capable of causing intrauterine embryopathies decreases worldwide, the relative importance of genetic bases for congenital malformations has increased. The identification, evaluation, and treatment of such disorders is multidisciplinary and, with few exceptions, should include the ophthalmologist. The key initial step is the establishment of a diagnosis to determine organ involvement, the spectrum of prognosis, affected status of relatives if desired, and recurrence risks for future offspring. About one half of visually impaired children have a heritable condition.
Historical information is useful and includes detailed prenatal, developmental, and family information. The prenatal history should include the ages of both mother and father and consanguinity as increased paternal age is associated with single gene mutations and increased maternal age is associated with chromosomal rearrangements. Review of previous pregnancies for miscarriages, stillbirths, and spontaneous abortions is useful, including prenatal testing; questions should be carefully phrased so as not to convey blame. Delivery information, birth weight, and Apgar scores can be very helpful in elucidating the state of the newborn infant. Known abnormalities at birth and details of initial hospitalization are helpful, for example, intracerebral bleeds, retinopathy of prematurity, surgery, and hospitalizations. Key questions include assessment of developmental milestones; the physician should distinguish between developmental delay and regression. The family history should delineate ocular disorders as well as other diseases such as seizures and developmental delay; for some disorders such as neurofibromatosis, cataracts, nystagmus, colobomata, and tuberous sclerosis, both parents should undergo an eye examination to determine the genetic basis. If one or more congenital abnormalities are present with delayed development and a diagnosis is not readily identifiable, chromosomal analysis should be obtained. A comprehensive eye exam should be performed on the patient. All families of patients with a genetic disease or the possibility of a genetic disease should undergo formal genetic evaluation by a geneticist to ensure understanding of the condition and reproductive alternatives; such referrals will minimize medical-legal risk for unexpected recurrence in future offspring.
Although there are many congenital/infantile abnormalities, we will limit our discussion to case studies of a few selected entities. The ocular findings of isolated ocular and periocular monogenic disorders (Table 8-1), ocular findings in multisystem syndromes (Table 8-2), ocular findings in metabolic disorders (Table 8-3), and ocular findings in selected chromosomal syndromes (Table 8-4) are summarized.
| Achromatopsia (rod monochromatism) Aniridia | Congenital absence of cone photoreceptors Absent iris tissue, glaucoma, foveal hypoplasia, cataracts | AR, XLR |
| Anterior megalocornea | Bilateral megalocornea, subluxed lenses | XLR |
| Axenfeld-Rieger anomaly | Posterior embryotoxin, iris strands, iris abnormalities | AD |
| Best disease | Bilateral retinal macular dystrophy | AD |
| Blepharophimosis-ptosis syndrome | Bilateral ptosis, epicanthus inversus, telecanthus | AD |
| Blue cone monochromatism | Nonprogressive disorder of cones, nystagmus, poor vision | XLR |
| Choroideremia | Progressive choriocapillaris and RPE degeneration | XLR |
| Congenital cataracts | Opacities of the crystalline lens | AD, AR, XLR |
| Congenital color blindness | Red-green color blindness or confusion | XLR |
| Blue-yellow confusion | AD | |
| Congenital hereditary endothelial bilateral dystorphy | Corneal haze, thickened cornea | AR > AD |
| Congenital-infantile glaucoma | Elevated intraocular pressure | AR |
| Congenital ocular fibrosis syndrome | Fibrosis of extraocular muscles, strabismus | AD > AR |
| Congenital stationary night blindness | Nonprogressive nyctalopia, variable visual acuity | AD, AR |
| associated with poor vision, nystagmus, myopia | XLR | |
| Cornea plana | Flat corneal curvature | AR, AD |
| Cryptophthalmos | Fusion of eyelids, brow abnormalities, microphthalmia | AR |
| Degenerative myopia | High myopia, lacquer cracks, RPE atrophy | AR |
| Distichiasis | Extra row of abnormal lashes along lid margin | AD |
| Duane syndrome | Abnormal ocular motility associated with lid elevation | AD |
| Ectopia lentis et pupillae | Bilateral eccentric pupils, subluxed lenses, miosis | AR |
| Epithelial basement membrane dystrophy | Cortical epithelial and basement membrane abnormalities | AD |
| Familial exudative vitroretinopathy | Peripheral retinal vascular abnormalities, RD | AD, XLR |
| Fleck corneal dystrophy | Corneal stromal opacities | AD |
| Fundus albipunctatus | Nonprogressive nyctalopia, midperipheral white dots | AR |
| Gelatinous droplike dystrophy | Localized corneal amyloidosis | AR |
| Goldmann-Favre syndrome | Bilateral vitreoretinal degeneration, nyctalopia | AR |
| Granular corneal dystrophy | Corneal stromal opacities | AD |
| Hereditary optic atrophy | Bilateral vision loss, optic nerve pallor | AD, AR |
| Jansen disease | Similar to Wagner disease, however RD common | AD |
| Keratoglobus | Corneal thinning, Descemet’s breaks, astigmatism | AR |
| Lattice corneal dystrophy | Corneal stromal opacities | AD |
| Leber congenital amaurosis | Generalized tapetoretinal degeneration, abnormal ERG | AR (AD rare) |
| Macular corneal dystrophy | Corneal stromal opacities | AR |
| Meesmann corneal dystrophy | Corneal intraepithelial cysts | AD |
| Megalocornea | Enlarged corneal diameter | AD |
| Microcornea | Decreased corneal diameter | AD, AR |
| Microphthalmia | Congenital reduction of ocular volume | AD |
| Ocular albinism | Nystagmus, iris transillumination, macular hypoplasia | AR, XLR |
| Oguchi disease | Nonprogressive nyctalopia | AR |
| Optic nerve drusen | Hyaline and/or calcium deposits in the optic disc | AD |
| Peters anomaly | Corneal opacification, lenticulocomeal adhesions | AR, AD |
| Posterior embryotoxin | Anteriorly displaced ring of Schwalbe | AD |
| Posterior polymorphous dystrophy | Opacities on posterior corneal surface | AD |
| Progressive cone dystrophy | Progressive cone dysfunction | AD |
| Reis-Buckler corneal dystrophy | Corneal dystrophy affecting Bowman’s layer | AD |
| Retinitis pigmentosa | Progressive degeneration of the photoreceptors | AD, AR, XL |
| Retinitis punctata albescens | White dots across retina, nyctalopia | AR |
| Schnyder crystalline dystrophy | Corneal stromal opacities | AD |
| Simple ectopia lentis | Subluxed lens | AD |
| Stargardt’s disease;fundus flavmaculatus | Bilateral retinal macular dystrophy | AR, AD |
| Uveal coloboma | Incomplete closure of embryonic fissure | AD, AR, XLR |
| Wagner disease | Vitreoretinal degeneration, myopia, cataracts, glaucoma | AD |
| X-linked retinoschisis | Stellate maculopathy, peripheral retinoschisis | XLR |
| AD = autosomal dominant, AR = autosomal recessive, XLR = X-linked recessive, RD = retinal detachment, ERG = electroretinogram, RPE = retinal pigment epithelium. | ||
| Disease | Ocular Manifestations | Inheritance |
|---|---|---|
| Osteogenesis imperfecta congenita | Corneal arcus, keratoconus, glaucoma, megalocornea blue sclera, cataracts | AR |
| van der Hoeve | Blue sclera | AD |
| Osteopetrosis | Cranial nerve palsies; optic atrophy | AR, AD |
| Robert | congenital cataracts | AR |
| Schwartz-Jampel | Blepharophimosis | AR |
| Spondyloepiphyseal dysplasia congentita | High myopia, vitreous syneresis, lattice degeneration of retina | AD |
| Stickler | High myopia, retinal detachments | AD |
| Weill-Marchesani | Ectopia lentis, shallow anterior chamber | AD |
| Wildervanck | Duane syndrome | ?? |
| Neurologic | ||
| Aicardi | Chorioretinal lacunar lesions | XD |
| Alpers diffusecerebral degeneration | Cortical blindness | AR |
| Ataxia-telangectasia | Tortuosity of conjunctival vessels | AR |
| Behr | Optic atrophy | AR |
| Caravan | Optic atrophy, nystagmus | AR |
| Charcot-Marie-Tooth | Optic atrophy, tonic pupils | AR, AD, XR |
| Familial dysautonomia (Riley-Day) | Decreased tear production, corneal hypesthesia, corneal breakdown with scarring, optic atrophy, corneal ulcers | |
| Infantile subacute necrotizing encephalomyelopathy | Optic atrophy, nystagmus | AR |
| Marinesco-Sjogren | Congenital cataracts | AR |
| Meckel-Gruber | Colobomatous microphthalmia | AR |
| Olivopontocerebellar (OPCAIII) | Retinal degeneration | AD |
| Sjogren | Congenital cataracts | AR |
| Sjogren-Larrson | Colobomatous microphthalmia | AR |
| Warburg | Microphthalmia, congenital retinal detachment | AR |
| Dermatologic Syndromes | ||
| Basal cell nevus | Colobomatous microphthalmia, cataract | AD |
| Cockayne | Juvenile cataracts, retinitis pigmentosa | AR |
| Cross | Microphthalmia | AR |
| Dyskeratosis congenita | Blepharitis, nasalacrimal duct obstruction | |
| Ectodermal dysplasia (anhidrotic) | Alacrima or decreased tear production | XR, AR |
| Ehlers-Danlos Type I, II, III Type VI | Retinal detachment Blue sclera, retinal detachment, sclera rupture, keratoconus, ectopia lentis | AD AR |
| Focal dermal hypoplasia (Goltz-Gorlin) | Conjunctival papillomas, colobomatous microphthalmia | XD |
| Hereditary benign intraepithelial dyskeratosis | Conjunctival gelatinous plaques, corneal dyskeratosis | AD |
| Histiocytic dermato-arthritis Ichthyosis | Glaucoma, uveitis, cataracts | AD |
| Congenital ichthyosis (harlequin fetus) | Ectropion, congenital cataracts | AD |
| Lamellar ichthyosis | Ectropion | AR |
| Ichthyosis vulgaris | Blepharitis, corneal erosions | AD |
| Bullous ichthyosiform erythroderma | Blepharitis | AD |
| X-linked, ichthyosis | Blepharitis, corneal erosions | XR |
| Incontinentia pigmenti | Infantile retinal detachment cataracts | XD |
| Lipoid proteinosis (Urbach-Wiethe) | Hyalinized deposition in mucous membrane and lids, corectopia | AR |
| Marfan syndrome | Ectopia lentis, glaucoma retinal detachment, myopia | AD |
| Melkersson-Rosenthal | VII nerve palsy and corneal exposure | AD |
| Pachyonychia congenita | Corneal dyskeratosis, cataracts | AD |
| Pseudoxanthoma elasticum | Blue sclera, angioid streaks, myopia, drusen | AR, AD |
| Rothmund-Tompson | Acquired cataracts | AR |
| Waardenburg | Lateral displacement of lacrimal punctae, heterochromia of irides, pigmentary, variability within or between fundi, strabismus | AD |
| Xeroderma pigmentosa | Lid telangectases, photophobia, conjunctivitis | AR |
| Craniofacial Syndromes | ||
| Cerebro-oculo-facial-skeletal | Microphthalmia, infantile Cataracts | AR |
| Cornelia de Lange | Long eyelashes, synophrys, optic atrophy | ?? |
| Cryptophthalmia | Fusion of eyelids, brow abnormalities, microphthalmia | AR |
| Goldenhar-Gorlin (oculoauriculo vertebral-dysplasia) | Epibulbar choristomas, strabismus, blepharoptosis, eyelid defects, optic nerve hypoplasia, tortuous retinal vessels, macular hypoplasia, microphthalmia, anophthalmia, lacrimal drainage system anomalies, colobomas | ?? |
| Hallermann-Streiff | Congenital cataracts, microphthalmia | ?? |
| Lenz microphthalmia | Microphthalmia, colobomatous or noncolobomatous | AR |
| Moebius | Congenital VI and VII nerve palsy, corneal exposure | AD |
| Reiger | Iris hypoplasia, pseudopolycoria, glaucoma | AD |
| Rubinstein-Taybi | Coloboma, glaucoma, cataract, strabismus, optic atrophy | ?? |
| Smith-Lemli-Opitz | Congenital cataracts | AR |
| Treacher Collins(Franceschetti) | Lid defects, antimongoloid slant to lids | AD |
| Whistling face(Freeman-Sheldon) | Ptosis | AD |
| William | Stellate pattern of iris, strabismus abnormalities of retinal vessels | |
| Hematologic Syndromes | ||
| Granulomatous disease (chronic) of childhood | Chorioretinal lesions, blepharitis | XR |
| Fanconi |
