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Albinism

Main Features

  • Oculocutaneous Albinism (OCA): Hypopigmentation of skin and hair with characteristic eye findings
  • Ocular Albinism (OA): Normal skin and hair pigmentation with characteristic eye findings

Eye Findings

  • Refractive error: significant myopia, hyperopia and/or astigmatism
  • Motility: Nystagmus, esotropia
  • Vision: Variable 20/40-20/200
  • Iris: Transillumination defects (from complete lack of pigmentation in OCA1 to variable small defects in OA)
  • Fundus: Hypopigmentation, foveal hypoplasia
  • Optic nerve function: Abnormal visual evoked potentials (representing abnormally high amount of decussation of ganglion cell fibers)

Etiology

  • OCA: autosomal recessive
    • OCA1A (commonly recognized type) occurs in 1/40,000 with 1/100 are carriers
      • Two TYR gene mutations (11q14-q21) causing no tyrosinase to be produced; no melanin
    • OCA1B: Two TYR gene mutations causing at least one copy of a partially active tyrosinase enzyme: less melanin
    • OCA2: P gene mutation (15q11.2-q12) hair pigmented but not skin, some iris pigment
    • OCA3: TYRP1 gene mutation (9p23) described in those of african descent
    • OCA4: MAPT gene mutation (SLC45A2)
    • Hermansky-Pudlak syndrome: mutation in any of HPS1 (10q23.1), HPS2 (5q13) , HPS3 (3q24), HPS4 (22q11.2-q12.2), HPS5-9
    • Chediak-Higashi syndrome: chromosome 1
  • OA: Ocular Albinism
    • OA1 gene mutations (Xp22): males with normal hair and skin pigment, abnormal melanosome production
      • giant melanosomes on skin biopsy if preformed, defect is in melanosome production
      • can have late onset sensorineural deafness
      • female carriers have mosaic pigmentation of peripheral fundus
    • OA2: Families from Aland Islands in the Sea of Bothnia, female carriers do not have a mosaic pattern, possibly a type of CSNB (310500), (Xp11.4-p11.23) OMIM: 300600,
    • OA3: Autosomal recessive. OMIM reference (6q13-q15) or (15q11.2-q12)
    • OA with sensorineural deafness: OMIM reference (11q14-q21, 3p14.1-p12.3)
      • Waardenburg Syndrome type II with ocular albinism, mutation in the transcription factor MITF which regulates the TYR gene

Relative Frequency Estimates

Type Gene Share of albinism cases worldwide Estimated prevalence Notable population patterns
OCA1 TYR 50% (most common in Caucasians) 1:40,000 globally Most common subtype in Europeans and Japanese (1/3 of Japanese OCA)
OCA2 OCA2 30% (most common form overall, driven by Africa) 1:37,000–40,000 (Caucasians); 1:10,000 (sub-Saharan Africa), up to 1:1,000 / 1:227 in isolates Most common subtype in Africa; high rates in some Native American groups (e.g., Hopi)
OCA3 TYRP1 3% 1:8,500 in southern Africa; nearly absent in Caucasians/Asians Largely restricted to African populations
OCA4 SLC45A2 17% 1:85,000 in Japan Most common type in Japan (25% of Japanese OCA); 5–8% of German cases
OCA5–8 4q24 locus, SLC24A5, LRMDA, DCTRare / not well defined Not well established Individually rare; prevalence poorly characterized
Ocular albinism (OA1) GPR143 (X-linked) 7% of molecularly diagnosed albinism series 1:50,000-60,000 males Primarily affects males

Other Findings

  • OCA1A: No pigment of hair or skin, coarse rough skin, unpigmented nevi, solar keratoses (premalignant) basal cell or squamous cell carcinomas (actually quite rare due to good prevention), skin melanocytes are present but melanoma rare
  • OCA1B: white to very light hair and skin at birth with variable amounts of darkening, pigmented nevi and freckles can develop
  • OCA2: Pigmented hair at birth, no generalized skin pigmentation but pigmented nevi and freckles can develop
  • OCA4: Variable pigmentation of skin and hair, similar to OCA2
  • Hermansky-Pudlak syndrome
    • Potentially lethal subtype
    • Bleeding diathesis
    • Pulmonary Fibrosis
    • Granulomatous colitis
  • Chediak-Higashi syndrome
    • Potentially lethal subtype
    • Congenital Immunodeficiency causing infections of skin and respiratory tract
    • Bleeding Diathesis
    • Progressive Neurodegeneration

References

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