The classification of congenital hypopigmentary diseases that result from a defect in the production of pigment (melanin) due to dysfunction of pigment cells (melanocytes) in the skin, the eyes, and/or the ears consists of the following: oculocutaneous albinism types 1-7; ocular albinism; Chediak-Higashi syndrome (see the image below); Hermansky-Pudlak syndrome; and Griscelli syndrome. [1, 2, 3, 4]
See 13 Common-to-Rare Infant Skin Conditions, a Critical Images slideshow, to help identify rashes, birthmarks, and other skin conditions encountered in infants.
Chediak-Higashi syndrome and Hermansky-Pudlak syndrome also manifest with extrapigmentary defects consisting of leukocyte, platelet, pneumocyte, and reticular cell dysfunction. Griscelli syndrome can also manifest with immunodeficiency and neurologic defects.
These diseases present with a generalized complete or partial loss in pigmentation of the skin and the hair. Mutations in genes that regulate the multistep process of melanin synthesis, distribution of pigment by the melanocyte, and/or melanosome biogenesis are the basis for these diseases. The proteins/gene products (and respective gene) affected in each form of oculocutaneous albinism are as follows:
Oculocutaneous albinism type 1 - Tyrosinase enzyme [11q14-21]
Oculocutaneous albinism type 2 - P protein [15q11-13]
Oculocutaneous albinism type 3 - Tyrosinase related protein-1 enzyme (TYRP1) [9p23]
Oculocutaneous albinism type 4 - A membrane-associated transport protein (MATP/SLC24A2) [5p13.3]
Oculocutaneous albinism type 5 - Protein unknown [4q24]
Oculocutaneous albinism type 6 - A membrane-associated transport protein (SLC24A5) [15q21.1]
Oculocutaneous albinism type 7 - Protein unknown [10q22.2-3]
The approximate incidences of these diseases are as follows:
Oculocutaneous albinism type 1 - One case per 40,000 population
Oculocutaneous albinism type 2 - One case per 36,000 population, except in Africans and African Americans, in whom the incidence is 1 case per 10,000 population
Oculocutaneous albinism type 3 - Unknown
Oculocutaneous albinism type 4 - One case per 100,000 population, except in Japan, where 24% of individuals with oculocutaneous albinism have this form
Oculocutaneous albinism type 5 - Unknown (reported in one family)
Oculocutaneous albinism type 6 - Unknown (reported in two individuals)
Oculocutaneous albinism type 7 - Unknown (reported in several individuals)
Ocular albinism - One case per 50,000 population
Chediak-Higashi syndrome - Extremely rare
Hermansky-Pudlak syndrome - Rare, except in Puerto Rico, where frequency is 1 case per 1800 population
Griscelli syndrome - Extremely rare
All races appear to be equally affected by the associated mutations. However, oculocutaneous albinism type 2 is reportedly more common among Africans and African Americans (1 case per 10,000 population) than in whites (1 case per 36,000 population).
The incidence of these albino diseases is equal for men and women.
All of these diseases present in neonates. Chediak-Higashi syndrome consists of an accelerated phase that occurs years to decades after birth.
Oculocutaneous albinism types 1, 2, 3, and 4 and ocular albinism are not associated with mortality and/or morbidity outside of cutaneous sensitivity to solar irradiation and the associated visual defects described below (see Physical).
Children with Chediak-Higashi syndrome manifest easy bruising, mucosal bleeding, epistaxis and petechiae, recurrent infections primarily involving the respiratory system, and neutropenia. Approximately 85% of individuals with Chediak-Higashi syndrome enter an accelerated phase, including fever; anemia; neutropenia; and, occasionally, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and jaundice. Neurologic problems are variable in Chediak-Higashi syndrome and include a peripheral and cranial neuropathy, autonomic dysfunction, weakness and sensory deficits, loss of deep tendon reflexes, clumsiness with a wide-based gait, seizures, and decreased motor nerve conduction velocities. Death usually occurs in the first decade from infection, bleeding, or development of the accelerated phase.
Individuals with Hermansky-Pudlak syndrome manifest a bleeding diathesis resulting from a platelet storage pool deficiency. They also develop a ceroid storage disease in which a ceroid-lipofuscin material accumulates in various organ systems, resulting in pulmonary fibrosis, granulomatous colitis, gingivitis, kidney failure, and cardiomyopathy. Pulmonary fibrosis usually proves fatal in the fourth or fifth decade of life. There are nine different genetic forms of Hermansky-Pudlak syndrome.
Most individuals with Griscelli syndrome develop chronic infections resulting from severe immunodeficiency that can be fatal within the first decade of life.
Patients should use broad-spectrum sunscreens and should wear appropriate clothing to prevent ultraviolet-induced damage to the skin. Visual impairment can be improved by using corrective lenses.