Ocular Albinism, X-Linked – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: X-linked ocular albinism (XLOA) is a disorder of melanosome biogenesis leading to minor cutaneous and adnexal manifestations and congenital and persistent visual impairment in affected males. XLOA is characterized by infantile nystagmus, reduced visual acuity, hypopigmentation of the iris pigment epithelium and the ocular fundus, and foveal hypoplasia. Significant refractive errors, reduced or absent binocular functions, photoaversion, and strabismus are common. XLOA is a non-progressive disorder and the visual acuity remains stable throughout life, often slowly improving into the mid-teens.

Diagnosis/testing: A diagnosis of ocular albinism (OA) is probable in the presence of infantile nystagmus, iris translucency, substantial hypopigmentation of the ocular fundus periphery in males with mildly hypopigmented skin (most notably when compared to unaffected sibs), foveal hypoplasia, reduced visual acuity, and aberrant optic pathway projection as demonstrated by crossed asymmetry of the cortical responses on visual evoked potential testing. X-linked inheritance is documented by either a family history consistent with X-linked inheritance or the presence of typical carrier signs (irregular retinal pigmentation and mild iris transillumination) in an obligate carrier female. Molecular genetic testing of GPR143 (previously OA1) detects pathogenic variants in more than 90% of affected males.

Management: Treatment of manifestations: Early detection and correction of refractive errors, use of sunglasses or special filter glasses for photoaversion, and prismatic spectacle correction for abnormal head posture. Strabismus surgery is often unnecessary but may be performed to improve peripheral visual fusion fields. The need for vision aids and special consideration in educational settings should be addressed.

Surveillance: For affected children younger than age 16 years: annual ophthalmologic examination (including assessment of refractive error and the need for filter glasses) and psychosocial and educational support. For adults: ophthalmologic examinations as needed.

Genetic counseling: XLOA is inherited in an X-linked manner. An affected male transmits the pathogenic variant to all of his daughters and none of his sons. The risk to the sibs of a male proband depends on the carrier status of the mother. If the mother is a carrier, the chance of transmitting the GPR143 pathogenic variant in each pregnancy is 50%. Male sibs who inherit the pathogenic variant will be affected; female sibs who inherit the pathogenic variant will be carriers and will usually not be affected. Carrier testing of at-risk female relatives is most informative if the pathogenic variant has been identified in the proband. Prenatal testing is possible for a pregnancy at increased risk if the familial pathogenic variant is known.