Hypopigmentation

Abstract: Oculocutaneous albinism (OCA) is a group of inherited disorders of melanin biosynthesis characterized by a generalized reduction in pigmentation of hair, skin and eyes. The prevalence of all forms of albinism varies considerably worldwide and has been estimated at approximately 1/17,000, suggesting that about 1 in 70 people carry a gene for OCA. The clinical spectrum of OCA ranges, with OCA1A being the most severe type with a complete lack of melanin production throughout life, while the milder forms OCA1B, OCA2, OCA3 and OCA4 show some pigment accumulation over time. Clinical manifestations include various degrees of congenital nystagmus, iris hypopigmentation and translucency, reduced pigmentation of the retinal pigment epithelium, foveal hypoplasia, reduced visual acuity usually (20/60 to 20/400) and refractive errors, color vision impairment and prominent photophobia. Misrouting of the optic nerves is a characteristic finding, resulting in strabismus and reduced stereoscopic vision. The degree of skin and hair hypopigmentation varies with the type of OCA. The incidence of skin cancer may be increased. All four types of OCA are inherited as autosomal recessive disorders. At least four genes are responsible for the different types of the disease (TYR, OCA2, TYRP1 and MATP). Diagnosis is based on clinical findings of hypopigmentation of the skin and hair, in addition to the characteristic ocular symptoms. Due to the clinical overlap between the OCA forms, molecular diagnosis is necessary to establish the gene defect and OCA subtype. Molecular genetic testing of TYR and OCA2 is available on a clinical basis, while, at present, analysis of TYRP1 and MATP is on research basis only. Differential diagnosis includes ocular albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, and Waardenburg syndrome type II. Carrier detection and prenatal diagnosis are possible when the disease causing mutations have been identified in the family. Glasses (possibly bifocals) and dark glasses or photocromic lenses may offer sufficient help for reduced visual activity and photophobia. Correction of strabismus and nystagmus is necessary and sunscreens are recommended. Regular skin checks for early detection of skin cancer should be offered. Persons with OCA have normal lifespan, development, intelligence and fertility.

Abstract: THE mouse pink-eyed dilution (p) locus on chromosome 7 is associated with defects of skin, eye and coat pigmentation1. Mutations at p cause a reduction of eumelanin (black-brown) pigment and altered morphology of black pigment granules (eumelano-somes), but have little effect on pheomelanin (yellow-red) pigment2. We show here that the human complementary DNA DN10, linked to thep locus in mice3–5, identifies the human homologue (P) of the mouse pgene, and appears to encode an integral membrane transporter protein. The expression pattern of this gene in various p mutant mice correlates with the pigmentation phenotype; moreover, an abnormally sized messenger RNA is detected in one mutant,pun, which reverts to the normal size in pun revertants. The human P gene corresponds to the D15S12locus within the chromosome segment 15qll–ql3, which is typically deleted in patients with Prader–Willi and Angelman syndrome (see ref. 5 for review). These disorders are phenotypically distinct, depending on the parent of origin of the deleted chromosome5–7, but both syndromes are often associated with hypopigmentation of the skin, hair and eyes (see ref. 8 for review), and deletion of theP gene may be responsible for this hypopigmentation. In addition, we report a mutation in both copies of the human P gene in one case of tyrosinase-positive (type II) oculocutaneous albinism, recently linked to 15qll–ql3 (ref. 9).

Abstract: PART I: THE PHYSIOLOGY OF THE PIGMENTARY SYSTEM SECTION 1: HISTORICAL & COMPARATIVE PERSPECTIVES OF THE PIGMENT SYSTEM SECTION 2: THE MORPHOLOGY, DISTRIBUTION & BIOLOGY OF THE PIGMENT CELL SECTION 3: THE MOLECULAR BIOLOGY OF THE PIGMENT CELL SECTION 4: CHEMISTRY & PHYSICS OF MELANIN AND ENZYMOLOGY OF MELANIN SYNTHESIS PART II: THE PATHOPHYSIOLOGY OF THE PIGMENTARY SYSTEM SECTION 5: AN OVERVIEW OF HUMAN SKIN COLOR AND ITS DISORDERS SECTION 6: DISORDERS OF HYPOPIGMENTATION AND DEPIGMENTATION SECTION 7: DISORDERS OF HYPERPIGMENTATION SECTION 8: TREATMENT OF PIGMENTARY DISORDERS

Abstract: Purpose of reviewChediak-Higashi syndrome, a rare autosomal recessive disorder, was described over 50 years ago. Patients show hypopigmentation, recurrent infections, mild coagulation defects and varying neurologic problems. Treatment is bone marrow transplant, which is effective in treating the hem