Oculocutaneous Albinism Type 1
Characteristics. Oculocutaneous albinism type 1 (OCA1) is characterized by hypopigmentation of the skin and hair and the distinctive ocular changes found in all types of albinism, including: nystagmus; reduced iris pigment with iris translucency; reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination; foveal hypoplasia with substantial reduction in visual acuity, usually in the range of 20/100 to 20/400; and misrouting of the optic nerve fiber radiations at the chiasm, resulting in strabismus, reduced stereoscopic vision, and altered visually evoked potentials (VEP). Individuals with OCA1A have white hair, white skin that does not tan, and fully translucent irides, none of which darken with age. At birth, individuals with OCA1B have white or very light yellow hair that darkens minimally with age, white skin that over time develops some minimal generalized pigment and may tan slightly with judicious sun exposure, and blue irides that darken to green/hazel or light brown/tan with age, although transillumination defects persist. Visual acuity may be 20/60 or better in some eyes.
Diagnosis/testing. The diagnosis of OCA1 is established by clinical findings of profound hypopigmentation of the skin and hair and characteristic ocular findings. Molecular genetic testing of TYR (encoding tyrosinase) is used infrequently in diagnosis, except to distinguish between types 1A and 1B, as the phenotypes may be nearly identical in the first year of life.
Management. Treatment of manifestations: Correction of refractive errors with spectacles or (when age-appropriate) contact lenses may improve visual acuity; strabismus surgery can be considered for either functional (improved peripheral fusion) or cosmetic reasons. Hats with brims and dark glasses or transition lenses often reduce discomfort in bright light (photodysphoria).
Protection from sun exposure with appropriate skin-covering clothing and sunscreens prevents burning, consequent skin damage, and the enhanced risk of skin cancer. Skin cancer, including a slightly enhanced risk for cutaneous melanoma, is treated as for the general population.
Surveillance: Annual ophthalmologic examination to reassess refractive errors and strabismus; routine skin examination of adults for evidence of sun-related skin damage and/or pre-cancerous or cancerous lesions.
Agents/circumstances to avoid: Prolonged sun exposure.
Genetic counseling. OCA1 is inherited in an autosomal recessive manner. In most situations, the parents of an affected individual are obligate heterozygotes, and therefore each carries one mutant allele. Heterozygotes (carriers) are asymptomatic. At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomaticcarrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing of pregnancies at increased risk are possible when both disease-causing mutations in an affected family member are known.
The diagnosis of oculocutaneous albinism type 1 (OCA1) [Creel et al 1990] is established by the presence of the following:
Hypopigmentation of the skin and hair (including brows and lashes) on physical examination
Infantile nystagmus (usually noticed between ages 3 and 12 weeks)
Markedly reduced iris pigment with iris transillumination
Reduced retinal (pigment epithelial) pigmentation with visualization of the choroidal blood vessels on ophthalmoscopic examination
Foveal hypoplasia associated with substantial reduction in visual acuity
Misrouting of the optic nerve fiber projections at the optic chiasm frequently associated with strabismus (that may not develop until later in infancy), reduced stereoscopic vision, and altered visually evoked potentials (VEP)
Note: The VEP is performed with a technique specifically designed to demonstrate selective misrouting; thus, a conventional simultaneous binocular VEP will not demonstrate this anomaly. Normal routing of the optic nerves, demonstrated with a selective VEP, excludes the diagnosis of albinism/OCA. The VEP is not necessary for the diagnosis of albinism because misrouting is implied by the observation of strabismus and reduced stereoscopic vision. In some persons with mild hypopigmentation (a few with OCA1B) and foveal hypoplasia and no obvious nystagmus, a VEP may be a useful adjunct to demonstrate misrouting of the retinal to occipital projections [Creel et al 1990, Pott et al 2003]. MRI studies may demonstrate misrouting but this approach is not validated sufficiently to replace VEP [Schmitz et al 2003].
Molecular Genetic Testing
Most individuals with OCA1 are compound heterozygotes with different paternal and maternal TYR mutations. No mutations in the proximal promoter of the gene have been identified.
Evidence that additional undetected mutations are responsible for OCA1 comes from individuals with the OCA1A phenotype with only a single identifiable mutation, but who are likely to be compound heterozygotes with a second, as-yet unidentified, mutation.