Albinism is a group of disorders characterized by reduced pigmentation resulting in ocular abnormalities with or without hypopigmentation of the skin and hair. The latter circumstance is referred to as oculocutaneous albinism (OCA). If only the eyes are affected, the patient has ocular albinism (OA).

Ocular manifestations of albinism include infantile nystagmus, iris transillumination (▶ Fig. 33.1), fundus hypopigmentation, macular hypoplasia (▶ Fig. 33.2), and gray optic nerves with or without optic nerve hypoplasia. Iris transillumination is perhaps the most constant feature although it rarely can be absent and sometimes is difficult to detect, especially in the presence of nystagmus. Visual acuity ranges between 20/40 and 20/400, depending primarily on the level of foveal hypoplasia. There is also a higher incidence of strabismus and refractive errors.

Differentiating OA, which is usually an X-linked recessive (XLr) disorder, from autosomal recessive (AR) and the uncommon autosomal dominant (AD) forms of OCA can be aided by examination of the parents. Carriers of all forms of albinism may show subtle, or even more frank, iris transillumination, most often in the inferior iris. Lyonization in female carriers of XLr OA (OA1) may result in irregular retinal pigmentation known as the “mud-splattered fundus,” with patches of retinal pigment epithelium (RPE) cells expressing the normal X chromosome, which are pigmented, interspersed with hypopigmented patches of RPE cells expressing the abnormal chromosome X (▶ Fig. 33.3). A careful search of the skin may reveal hypopigmented patches also due to lyonization.

33.2 Molecular Genetics

Tyrosinase, encoded by the TYR gene, is the key enzyme involved in melanin synthesis, through the hydroxylation of tyrosine to L-DOPA (L-3,4-dihydroxyphenylalanine) and the oxidation of L-DOPA to DOPAquinone. There are two types of melanin: eumelanin, which is a darker pigment commonly associated with tanning, and pheomelanin, which is responsible for yellow, orange, and reddish coloration. When eumelanin production is reduced, the pathway is shunted toward pheomelanin production.

Melanin is located in intracellular vesicles called melanosomes, most often found in melanocyte cells. In the eye, melanin is found in the iris-pigmented posterior epithelium, phagocytic clump cells in the iris stroma, retinal pigmented epithelium, and choroidal melanocytes.

Albinism has a gene-based nomenclature (▶ Table 33.1).

33.3 Differential Diagnosis

The presence of iris transillumination is usually abnormal even in lightly pigmented ethnic groups but can occur in other conditions, such as trauma, secondary atrophy (e.g., herpetic uveitis), and prematurity. Albinism should be considered in any child with nystagmus, but in the absence of other cardinal signs, such as iris transillumination or macular hypoplasia, nystagmus is not due to albinism. Macular hypoplasia can be due to isolated PAX6 mutation or with aniridia, both not associated with iris transillumination. Prematurity can be a cause of iris transillumination. The three-lead visual evoked potential (VEP) may show asymmetric decussations in any condition that leads to signal asymmetry, such as unilateral anophthalmia, severe microphthalmia, or severe amblyopia.

33.3.1 Åland Island Eye Disease (OMIM 300600)

This XLr condition is characterized by fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect, progressive myopia, and defective dark adaptation. Because of fundus hypopigmentation, it has been labeled as a form of albinism, but there is no misrouting of the optic nerves in the three-lead VEP. Iris transillumination may be seen. This condition is caused by mutation in the CACNA1F gene, which also causes XLr incomplete congenital stationary night blindness (CSNB2A; OMIM 300071).

33.3.2 BADS (Behavioral Assessment of the Dysexecutive) Syndrome (OMIM 227010)

This phenotype, also known as ermine phenotype, includes OA, black lock, and deafness. Molecular cause is unknown.

33.3.3 Griscelli Syndrome Type 1 (OMIM 214450)

This rare AR disorder is characterized by hypomelanosis with a primary neurologic deficit but without immunologic impairment or manifestations of hemophagocytic syndrome. It is caused by mutations in the gene encoding myosin VA (MYO5A; 15q21.2). Griscelli syndrome with immune impairment is known as Griscelli syndrome type 2 (RAB27A gene). Griscelli syndrome type 3 is characterized by hypomelanosis with no immunologic or neurologic manifestations (MLPH or MYO5A genes).

33.3.4 Elejalde Syndrome (OMIM 256710)

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