Genetics
Genetics Of Ocular Conditions
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Get access| Condition | Features | Genes implicated |
| RP | ||
| X-linked | Early onset Night blindness, progressive VF constriction and loss of vision Least common but most severe | Xp11.3 (RP2) Xp21 (RP3) |
| Autosomal dominant | Most common and best prognosis | Rhodopsin gene at 3q Peripherin gene at 6p |
| Lebers congenital amaurosis | An autosomal recessive form of RP | Null mutations in guanylate cyclase or homozygous defects of RPE 65 (this protein influences 11-cis-retinol formation) |
| Choroideraemia | Childhood onset Night blindness and later loss of vision Granular pigmentary changes initially, then choroidal atrophy later. Patchy non progressive equatorial pigmentary changes | Xq21 locus: deletion to Rab1 gene X-linked recessive |
| Norrie’s disease | Males affected from birth With bilateral congenital blindness Retinal dysplasia Retinal vascular changes Retinal detachment CataractDeafness and LD | Xp11.1 Xp11.3 |
| Achromatopsia | Homozygous (?recessive) defect in the cone cGMP-gated channel alpha subunit | |
| Red-green colour blindness | X-linked recessive | |
| Blue-cone monochromatism | X-linked recessive | |
| Retinoschisis | X-linked | |
| Albinism | Poor VA and nystagmus in children | |
| Oculocutaneous | Tyrosinase positive group Tyrosinase negative group (severe disease): profound visual loss, photophobia, nystagmusIris transillumination, absent fundal pigmentation, absent foveal reflex Most optic nerve fibres cross at the chiasma (VEP abnormalities see above) | Autosomal recessive |
| OcularAka Nettleship-Falls albinism | Most hypopigmentation confined to the ocular structures Giant melanosomes in the RPE, iris translucency, strabismus, nystagmus | X-linked recessive |
| Leber’s hereditary optic neuropathy | Males affected more than females Hyperaemic disc swelling Peripapillary telangiectasia Optic atrophy and optic nerve demyelination Visual failure: the papillomacular bundle is most severely affected | Suspected mitochondrial inheritance since males cannot transmit (although this does not explain the male predominance) Involves an NADH dehydrogenase typically |
| Kearns-Sayre syndrome | Pigmentary retinopathy Progressive myopathy including cardiac muscle Progressive external ophthalmoplegia | Mitochondrial inheritance Multiple point mutations |
| Chronic progressive external ophthalmoplegia | Ptosis, myopathy, depression, cataract, ketoacidosis | Mitochondrial or autosomal dominant inheritance (occasionally spontaneous de novo mutation) |
| Stargardt’s disease | Mild defects cause macular degeneration, intermediate defects cause cone-rod dystrophy, severe defects cause RP | Autosomal recessive. Defects in the ATP-binding cassette (ABCA4) transporter (see above, Rim proteins). Chromosome 1p abnormality |
| Goldmann-Favre disease | Optically empty vitreous Hyperopia | Autosomal recessive |
| Homocystinuria | Autosomal recessive | |
| Familial ectopia lentis | Autosomal recessive | |
| Macular corneal dystrophy | Least common but most severe of major stromal corneal dystrophies Grey-white opacities in stroma extending to periphery without clear spaces between | Autosomal recessive |
| Aniridia | Autosomal dominant (1/3rd are sporadic). Deletions of PAX-6 on chromosome 11 | |
| Best disease (vitelliform dystrophy) | Macular degeneration involving the entire RPE layer but only damaging the macula | Autosomal dominant. Heterozygous missense mutations of the bestrophin gene (BEST1) and PRPH2 (peripherin 2) gene |
| Ehler-Danlo’s syndrome | Autosomal dominant | |
| Stickler’s syndrome | High myopia Retinal detachment | Autosomal dominant (variable expressivity) 60% of patients have a mutation in the COL2A1 gene |
| Marfan’s syndrome | Autosomal dominant: fibrillin gene on chromosome 15 | |
| Myotonic dystrophy | 1 in 20,000 Expressionless face Frontal balding Gonadal atrophy Myotonia Cataracts Pigmentary retinopathy Cardiac arrhythmias | Autosomal dominant Chromosome 19 loci Triplet expansion: demonstrates anticipation. Congenital MD is most severe |
| NF-1 | Neurofibromas, optic nerve glioma | Autosomal dominant Chromosome 17q |
| NF-2 | Acoustic neuromas, gliomas, meningiomas | Autosomal dominant Chromosome 22q |
| Von Hippel-Lindau | Retinal angiomata Cerebellar haemangioblastoma | Autosomal dominant Chromosome 3 (VHL gene) |
| Tuberous sclerosis | Fundal astrocytomas | Autosomal dominant Chromosome 9q and 16p (TSC1 and TSC2 genes) |
| Gorlin-Goltz syndrome | Early development of multiple BCCs. Benign jaw tumours, rib and vertebral abnormalities, intracranial calcification, ovarian and cardiac fibromas | Autosomal dominant Chromosome 9 PTCH1 gene: produces patched-1 protein which interacts with sonic hedgehog during development |
| Retinoblastoma | 13q14 (chromosome 13) Appears autosomal dominant but both alleles need to be affected Majority of bilateral and unilateral cases are actually sporadic | |
| Turner’s syndrome | Short stature Hypertension Eyelid pigmentation Epicanthic folds Cataract Ptosis Strabismus Nystagmus | 45, X0 Non-dysjunction is usually paternal (ie. occurs in the spermatozoon) |
| Klinefelter’s syndrome | Tall Bilateral gynaecomastia (breast ca risk) Infertility, hypogonadism | Non-dysjunction during meiosis I47 XXY 47 XXXYY 47, XXYY |