Albinism: modern molecular diagnosis.

Albinism is no longer a clinical diagnosis. The past classification of albinism was predicated on phenotypic expression, but now molecular biology has defined the condition more accurately. With recent advances in molecular research, it is possible to diagnose many of the various albinism conditions on the basis of genetic causation. This article seeks to review the current state of knowledge of albinism and associated disorders of hypopigmentation. The term albinism (L albus, white) encompasses genetically determined diseases that involve a disorder of the melanin system. Each condition of albinism is due to a genetic mutation on a diVerent chromosome. The cutaneous hypopigmentation in albinism ranges from complete absence of melanin to a minimal reduction in skin and hair colour. On the other hand, the ocular phenotypic characteristics of most types of albinism are rather constant and include reduced visual acuity, nystagmus, pale irides that transilluminate, hypopigmented fundi, hypoplastic foveae, and lack of stereopsis. Pleiotropy is exhibited by all types of albinism; single gene mutations have eVects on diVerent organ systems. The most obvious systems involved are the integument and the eyes, but the nervous, haematological, respiratory, and gastrointestinal systems may occasionally be aVected. Three major mechanisms exist by which mutations exert their eVect on the pigmentation process. Firstly, abnormal pigmentation may occur early in the pathway of diVerentiation of melanocytes. Melanoblasts from the neural crest might be aVected along with cells from the same lineage, such as occurs in Waardenberg and Waardenberg– Hirschsprung syndrome where the melanocyte fails to populate certain areas during embryogenesis. Secondly, a mutation can aVect the melanin biochemical pathway causing a more specific abnormality. Oculocutaneous albinism type 1 (OCA 1) is an example of such a condition. Thirdly, the biogenesis of intracellular organelles of diVerent cells may need a common set of genes and one gene mutation could aVect seemingly unrelated cell types, including the melanocyte. Chediak–Higashi and Hermansky–Pudlak syndromes are disease examples.