Oculocutaneous Albinism Type 4

Clinical characteristics: Oculocutaneous albinism type 4 (OCA4) is characterized by hypopigmentation of the hair and skin plus the characteristic ocular changes found in all other 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 associated with reduction in visual acuity; and misrouting of the optic nerves at the chiasm associated with alternating strabismus, reduced stereoscopic vision, and an altered visual evoked potential (VEP). Individuals with OCA4 are usually recognized within the first year of life because of hypopigmentation of the hair and skin and the ocular features of nystagmus and strabismus. Vision is likely to be stable after early childhood. The amount of cutaneous pigmentation in OCA4 ranges from minimal to near normal. Newborns with OCA4 usually have some pigment in their hair, with color ranging from silvery white to light yellow. Hair color may darken with time, but does not vary significantly from childhood to adulthood.

Diagnosis/testing: Because the phenotype of OCA4 overlaps that of the other genetic forms of albinism (oculocutaneous and ocular), the diagnosis of OCA4 is established by molecular genetic testing with the identification of biallelic pathogenic variants in SLC45A2. A multigene panel or comprehensive genomic testing is the preferred molecular genetic testing method for this disorder.

Management: Treatment of manifestations: Correction of refractive errors with spectacles or contact lenses to improve visual acuity. Strabismus surgery may be considered for cosmetic reasons. Dark glasses may alleviate photophobia but may reduce vision; a hat with a brim or visor best achieves reduction in photophobia. Protection from the sun, through the wearing of protective clothing and the regular application of sunscreen, is essential.

Prevention of secondary complications: Individuals with OCA4 should stay out of the sun from an early age, because cumulative ultraviolet exposure is a major risk factor for skin cancers.

Surveillance: Annual ophthalmologic examination and reassessment for accurate correction of refractive error. Evaluation of the skin for cancer screening every six months is recommended.

Agents/circumstances to avoid: Prolonged exposure to sun.

Genetic counseling: OCA4 is typically inherited in an autosomal recessive manner. The parents of a proband are obligate heterozygotes and thus carriers of one SLC45A2 pathogenic variant. Heterozygotes (carriers) are asymptomatic and not at risk of developing the disorder, but may be light in pigmentation for their ethnic group. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.