Albinism

Excerpt

Albinism, from the Latin albus, meaning "white," is a group of heritable conditions associated with decreased or absent melanin in ectoderm-derived tissues (most notably the skin, hair, and eyes), yielding a characteristic pallor. The most commonly thought of presentation is that of oculocutaneous albinism (OCA). OCA is a group of phenotypically similar genetic disorders derived from errors in melanin synthesis. As the name implies, the most dramatic effects are in the eyes and skin. The skin manifestations are more heterogeneous and appear along with a spectrum of severity depending upon the subtype of OCA. The ocular structures rely upon melanin for signaling as they develop, in utero; thus, misrouted optic nerve fibers yield more uniform ocular manifestations of the disorder.

To date, seven types of nonsyndromic albinism (OCA1 to OCA7) have been described. These are all due to isolated genetic mutations whose constellation of signs and symptoms do not manifest so broadly that they can be classified as syndromic. A discussion on albinism, however, would be incomplete without the mention of isolated ocular albinism (OA1) and the syndromic albinisms: Hermansky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS). The syndromic albinisms have the same hallmark lack of dermal and ocular pigment as OCA. They, however, involve genes that encode for proteins that have more extensive applications to cellular function. Loss-of-function mutations in these genes, therefore, yield predictable systemic consequences associated with the syndromes mentioned. Examples include inactivation of genes involved in lysosomal synthesis (and not simply melanin synthesis) that lead to bleeding diathesis in HPS and propinquity to infection in CHS. Other conditions may present like albinism with congenital nystagmus and/or generalized hypopigmentation. Most of these are included in the Differential Diagnosis section. Of special mention is a pair of syndromes that derive their albino-like features because of deletions in the same genes that are mutated in OCA type 2: Angelman (AS) and Prader-Willi (PWS) syndromes.