Albinism refers to a heterogeneous group of hypopigmentation disorders that share an absolute or relative inherited deficiency of the pigment melanin that leads to characteristic changes in the skin, hair, and visual system (eyes and optic tracts). Melanin is produced and contained within melanosomes, intracellular organelles that are present in the stratum basale of the epidermis, hair bulbs, and intraocular epithelia. Most individuals with albinism have a simple, or nonsyndromic, form that affects the visual system, hair, and skin (oculocutaneous albinism, OCA) or mainly the visual system (ocular albinism, OA). Less commonly, individuals may have a complex, or syndromic, form of albinism that includes a distinctive pattern of organ involvement in addition to OCA. In recent years, much progress has been made in understanding the clinical features, pathophysiology, and molecular basis of albinism ( Box 60.1 ).

Box 60.1


  • Albinism is a heterogeneous group of disorders

  • Melanin pigment is deficient in all forms of albinism

  • Hypopigmentation affects the eyes, skin, and hair to varying degrees

  • Identification of ocular features is essential for the diagnosis of albinism

Clinical background

Individuals with albinism are typically fair of skin and hair and have hypopigmentation of ocular structures ( Figure 60.1 ). The degree of cutaneous hypopigmentation can vary greatly, ranging from the classic image of the albino with white hair, white skin, and pink-red irides to one in which no apparent cutaneous hypopigmentation is present. More constant are the effects that albinism has on the eye and visual pathways. Consequently, examination of the eyes remains an essential step for the diagnosis of albinism.

Figure 60.1

The phenotypic spectrum of albinism. Pigmentation ranges from white to dark hair with photophobia being conspicuous in those with the most marked deficits in pigment. Each of these individuals has ocular features of albinism.

(Reproduced with permission from Spekreijse H, Apkarian P. The use of a system analysis approach to electrodiagnostic (ERG and VEP) assessment. Vis Res 1986;26:195–216. )

The key ocular symptoms and signs are intimately related ( Table 60.1 ). Deficits in iris pigmentation typically impart a gray or blue color to the irides, which transilluminate light ( Figure 60.2A and B ). Foveal hypoplasia and mild optic nerve hypoplasia are typical ( Figure 60.2C ), as is nystagmus. The foveal reflex is almost always absent. The ocular fundi appear pale with the choroidal vasculature visible through the neurosensory retina and retinal pigment epithelium ( Figure 60.2D ). Strabismus and high refractive errors are common ( Box 60.2 ).

Table 60.1

Ocular features of albinism

Low acuity
High refractive errors
Irides that transilluminate light
Foveal hypoplasia
Fundus hypopigmentation

Figure 60.2

Typical ocular features in individuals with albinism. (A and B) The irides have sites that transilluminate light. At times the sites that lack pigment are punctate, microscopic areas which are visualized only by using high magnification of the slit lamp with the beam adjusted to fill the pupil with a reddish glow. (C) In albinism, the foveal pit is blunted or not identifiable. Normally the pit appears like a dimple made by a pebble hitting the shiny surface of a car. In this eye there is sufficient normal pigment to obscure the choroidal vasculature at the center of the macula. The optic nerve head is clinically normal although measurement of the diameter indicates that there is mild but statistically significant hypoplasia of the optic nerve head, consistent with the results of a structural magnetic resonance imaging study of the optic nerve and chiasm in albinism. The retinal vasculature is of normal caliber although, as pointed out by Neveu et al, the temporal arcades have a wider arch than seen in nonalbinotic fundi. The extramacular fundi are albinotic. (D) This photograph shows the posterior pole of another individual with albinism. Throughout the macula, the choroidal vasculature is visible through the neural retina and pigment epithelium as there is insufficient normal pigment. (E) Composite fundus photograph of a woman who is a carrier for X-linked ocular albinism. The pigmentation is uneven in the extramacular retina with scattered geographic areas of hypopigmentation. This woman had healthy eyes with superb visual acuity and no nystagmus.

Box 60.2

Common ocular features

  • Low visual acuity

  • Nystagmus

  • Iris sites that transilluminate light

  • Foveal hypoplasia

  • Hypopigmented fundi

  • Strabismus

  • High refractive errors

Acuity is low, ranging from a legal blind level to only mild acuity deficits; median acuity is often cited as approximately 20/60. The low acuity is secondary to foveal hypoplasia ; nystagmus may also degrade acuity. Anomalous head posture is used to counteract the effects of the nystagmus. Depth perception may be poor; typically no stereopsis is demonstrated. Strabismus is common, with esotropia more frequent that exotropia. High refractive errors are common in albinism, apparently from failure of emmetropization. In children with albinism, the ophthalmologist must be alert to amblyopia superimposed on the acuity deficit directly related to the foveal hypoplasia. In a child with albinism, as in other children, asymmetric acuity should alert the ophthalmologist to possible amblyopia associated with strabismus or with difference in refractive error between right and left eye, anisometropia.

The lack of the protective effect of melanin in the eye underlies photophobia. The individual with albinism is also at risk for sunburn rather than tanning, and for malignancies of the skin, especially if exposed unprotected to intense tropical sun.


From biblical times albinism has been recognized; it has been argued that Noah was an albino ( Box 60.3 ). There is a long, anecdotal history of albinism throughout the animal kingdom with notable ocular features. Foveal hypoplasia was recognized and documented histologically by Elschnig and a paucity of nondecussated fibers at the chiasm was reported in classical studies of the visual system in albino animals. In human subjects with albinism, electrophysiological and, more recently, functional magnetic resonance imaging studies have demonstrated anomalous organization of the visual pathways.

Box 60.3


  • Albinism has been recognized since biblical times

  • Structural and functional anomalies of the visual pathways have been substantiated

  • Molecular genetic basis for simple and complex forms of albinism has been delineated

For many years albinism was classified on a biochemical basis as tyrosinase-positive or tyrosinase-negative in the hair bulb incubation test. However, this test is seldom performed today because of its lack of sensitivity and specificity, giving rise to many false negatives and false positives; for example, patients with OCA1B and OCA2 have different genetic bases for their albinism, but both yield tyrosinase-positive results in the hair bulb test. Conversely, OCA1A and OCA1B are caused by the same gene but give rise to tyrosinase-negative and tyrosinase-positive results, respectively.

Gradually the genetic foundation for the simple forms of albinism has been established. Four autosomal-recessive genes for OCA and one gene for X-linked OA have been identified ( Table 60.2 ). OCA types 1–4 are inherited with equal frequency in males and females. The recurrence risk to couples with an affected child is 25% with each pregnancy. The ophthalmic characteristics of OCA1–4 are listed in Table 60.1 . OA1 follows an X-linked pattern of inheritance with affected hemizygous males, and female carriers who have healthy eyes, normal vision, and uneven fundus pigmentation ( Figure 60.2E ). Males with OA share essentially the same ophthalmic characteristics of those with OCA. All daughters of fathers with X-linked OA are obligate carriers, and carriers have a 50% chance of having an affected son (or carrier daughter) with each pregnancy.

Table 60.2

Genetic forms of albinism

Albinism type OMIM Gene symbol Historical name Protein Estimated frequency Chromosomal location Cellular defect Clinical features

  • OCA1A

  • OCA1B

  • 203100

  • 606952


  • Tyrosinase-negative

  • Tyrosinase-positive

Tyrosinase 1/40 000 11q14-q21

  • Synthesis of melanin

  • Retention in endoplasmic reticulum

  • 1A: White hair and skin at birth, no freckling, poor acuity

  • 1B: Cream skin and yellow-tinged hair at birth; some progressive pigmentation over time; improved vision over time

OCA2 203200 OCA2 Tyrosinase-positive P-protein 1/36 000 15q11.2-q12 Melanosome membrane protein involved in processing and transport of tyrosinase and other melanosomal proteins in small vesicles immediately post-Golgi Cream skin and yellow-tinged hair; some progressive pigmentation over time; improved visual acuity over time. High prevalence in Africa
OCA3 203290 TYRP1 Rufous albinism Tyrosinase- related protein Unknown 9p23 Binds to tyrosinase, function unclear. Retention in endoplasmic reticulum Red hair and red-brown skin. High prevalence in sub-Sahara Africa and New Guinea
OCA4 606574 SLC45A2 MATP Rare outside Japan 5p13.3 Processing and transport of tyrosinase to melanosomes Similar to OCA2
OA, type 1 300500 OA1 Nettleship–Falls GRP143 1/50 000 Xp22.3 Regulation of melanosome number and size

  • Ocular features of albinism with normal skin and hair pigmentation.

  • Female carriers have uneven pigmentation in retina and megamelanosomes in skin

Hermansky–Pudlak syndrome

  • 604982

  • 608233

  • 606118

  • 606682

  • 607521

  • 607522

  • 607145

  • 609762

  • HPS1

  • HPS2

  • HPS3

  • HPS4

  • HPS5

  • HPS6

  • HPS7

  • HSP8


  • HPS1

  • AP3B1

  • HPS3

  • HPS4

  • α-Integrin BP63

  • HPS6

  • DTNBP1

  • BLOC1S3

1/1800 among Puerto Ricans

  • 10q23.1

  • 5q14.1

  • 3q24

  • 22q11.2-22.2

  • 11p15-13

  • 10q24.32

  • 6p22.3

  • 19q13

Biogenesis of specialized organelles of endosomal lysosomal system, including melanosomes and platelet-dense bodies Bleeding diathesis, restrictive lung disease, pulmonary fibrosis, inflammatory bowel disease
Chédiak–Higashi syndrome 214500 CHS1 Same LYST Rare 1q42.1-q42.2 Lysosomal trafficking regulator Immunodeficiency, neutropenia, malignant lymphoma, large lysosomal granules
Prader–Willi syndrome 176270 Absence of paternally expressed genes at 15q11-13, including SNRPN, Necdin, P-gene Same SNRPN, Necdin, P-protein, possibly others 1/15 000 (1% have albinism) 15q11-13 P-gene-related and possibly other pigmentary genes Obesity, hypotonia, mental retardation, short stature, hypogonadotrophic hypogonadism, almond-shaped eyes, narrow bifrontal diameter of skull, small hands and feet, food obsession, skin-picking behavior, sleep apnea
Angelman syndrome 105830

  • Absence of maternally expressed genes at 15q11-13, including

  • UBE3A, P-gene

Happy puppet syndrome UBE3A, P-protein, possibly others 1/15 000 (1% have albinism) 15q11-13 P-gene-related and possibly other pigmentary genes Ataxia, mental retardation, absent speech, inappropriate laughter, seizures, microcephaly, prognathism, widely spaced teeth, poor sleep

The genetic basis has also been determined for a number of complex forms of albinism that have systemic comorbidities ( Table 60.2 ). In contrast, the simple forms of albinism ( Table 60.2 ) do not lead to systemic comorbidities.

The overall frequency of albinism in the general population is estimated to be 1 in 17 000, and about 1 in 65 individuals is a carrier for OCA. The frequency varies with specific type ( Table 60.2 ) and with ethnicity. An estimated 18 000 individuals in the USA have a form of albinism. OCA1 and OCA2 are the two most common forms of albinism and occur with similar frequencies.

Diagnostic workup

A history of nystagmus, decreased visual acuity, and fair skin and hair within the family group raises the suspicion for albinism ( Box 60.4 ). Inspection of the ocular structures adds diagnostic information. Typically, the irides transilluminate light ( Figure 60.2A and 60.2B ). Foveal hypoplasia and albinotic fundi ( Figure 60.2c and 60.2D ) are the main fundus features; mild optic nerve hypoplasia may also be present. The optic nerve head in children with albinism is significantly smaller than in normally pigmented, age-similar children, being about 80% of the normal mean diameter (AB Fulton, personal observation).

Aug 26, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Albinism

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