Ocular and Oculocutaneous Albinism
Title: Ocular and Oculocutaneous Albinism
Authors: Jenna Jensen; M. Margarita Parra, MD
Photographer: JMEC photographers
Keywords/Main Subjects: Albinism; Oculocutaneous albinism; Ocular albinism; Foveal hypoplasia; Hermansky-Pudlak Syndrome; Chediak Higashi Syndrome; Retina; Retinal Pigment Epithelium
Diagnosis: Ocular Albinism, Oculocutaneous Albinism
Brief Description: Albinism is a group of heterogeneous disorders with impairment of melanin pigment biosynthesis as a common pathophysiological pathway. Different mutations lead to the variable phenotypes including nonsyndromic types, such as oculocutaneous albinism and ocular albinism, and syndromc albinism. Ocular signs include nystagmus, uveal and retinal pigment epithelium hypopigmentation, foveal hypoplasia and abnormal retinostriate projections. The diagnosis can be made clinically in some cases, but genetic testing is very important to determine the type and if there is an associated systemic condition. Visual evoked potentials can also be performed. In addition, early refractive correction is important.
Comparison of RPE pigmentation and fovea between eyes with albinism and a normal eye
Grades of iris transillumination in eyes with albinism
Prevalence and Gender: Collectively, the group of disorders affects approximately 1/17,000 people worldwide. The most common type of albinism world-wide and Africa is oculocutaneous albinism type 2. Oculocutaneous albinism type 1 is common in America and Asia, and oculocutaneous albinism type 3 is found in South Africa. Hermansky-Pudlak syndrome is relatively common in Puerto Rico and in an isolated village in the Swiss Alps. However, all forms of albinism can be found throughout the world.
Albinism presents in both males and females. Males affected with ocular albinism typically express only the ocular features of albinism.
Genetics: Most forms of albinism present with autosomal recessive inheritance, except ocular albinism and Chediak-Higashi syndrome, which have X-linked recessive patterns.
Albinism is characterized by a genetic defect in melanin production, transport, trafficking, or maintenance. Phenotypic patterns are dependent on the level of the defect in the enzymatic pathway of melanin production.
The most common types of albinism and their genetic mutations summarized below.
- Oculocutaneous albinism type 1 (OCA1) , tyrosinase related: mutations in the TYR gene that encodes tyrosinase.
- Oculocutaneous albinism type 2 (OCA2)al, tyrosinase positive: defect in P gene on chromosome 15 within the Prader-Willi and Angelman syndrome region. The P gene encodes a protein responsible for maintenance of acidic pH in melanosomes.
- Oculocutaneous albinism type 3 (OCA3) , rufous albinism: mutation in the TYRP1 gene, which normally forms a protein that stabilizes the melanogenic enzyme complex during melanin synthesis.
- Oculocutaneous albinism type 4 (OCA4): defect in a gene that encodes a membrane-associated transporter protein, similar to oculocutaneous albinism type 2.
- Ocular albinism (OA1), Nettleship-Falls Type: defect in gene GPR143 in the Xp22 region, clinically similar to OCA without skin and hair hypopigmentation.
- Hermansky Pudlak Syndrome: Defect in 10 genes that encode lysosome proteins and are associated with the formation of vesicles, including melanosomes.
- Chediak-Higashi Syndrome: defect in the lysosomal trafficking regulator gene, which is responsible for a product involved in regulation of lysosomal trafficking.
Symptoms and signs: These include highly variable cutaneous and hair hypopigmentation, visual acuity ranging from 20/20 to 20/600, nystagmus that starts in early infancy, and strabismus. Uveal and retinal pigment epithelium hypopigmentation leads to iris translucency and visualization of choroidal vessels in the macula (macular transparency) and periphery.
Structural changes also include excessive decussation of retinostriate nerve projections. Abnormal crossing can be detected by visual evoked potentials. Foveal hypoplasia is present and noted as an absence or flattening of the normal foveal pit. This finding can be appreciated by optical coherence tomography.
Environmental Factors and other Considerations: No environmental factors are known to be involved in the pathophysiology of albinism. However, living near the equator, high altitude or without protection from the sun can contribute to skin cancer. Therefore, appropriate protection is recommended.
Pathophysiology: In normal embryonic development, melanin accumulates in the retinal pigment epithelium. Decreased levels of melanin results in misrouted optic nerve fibers, retinal hypopigmentation, and decreased visual acuity due to foveal hypoplasia.
Diagnosis: Albinism can be clinically apparent, but genetic testing is necessary to determine the type of albinism. It is important to determine conditions such as Hermansky Pudlak Syndrome, which is associated with bleeding diathesis, and predisposition to granulomatous colitis, interstitial lung disease and immunodeficiency. Chediak Higashi syndrome is associated with bacterial infections and a bleeding disorder. Over time, peripheral neuropathy can develop.
Differential Diagnosis: Rarer hypopigmentation disorders, such as Cross syndrome, should be considered depending on the age at presentation and other symptoms. Some ophthalmic disorders can be suspected in patients without cutaneous hypopigmentation, such as achromatopsia, isolated foveal hypoplasia, incomplete congenital stationary night blindness, Stickler syndrome, prematurity, as examples.
Treatment: There is currently no definitive treatment regimen; however ongoing ophthalmology care is needed. Vision rehabilitation including early refractive correction as patients have high refractive errors. Also, photochromic lenses are useful to alleviate photosensitivity and ultraviolet protection is important required. Consultation with dermatology and genetic counseling is recommended.
References: Hartnett ME. Pediatric retina. 3er edition. Philadelphia: Lippincott Williams & Wilkins. 2021. Section IV. Genetics and developmental disorders in pediatric retina. Pages 280- 295.
Faculty Approval by: M.E. Hartnett, MD
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