An Bras Dermatol. 2019;94(5):503---520 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br CONTINUING MEDICAL EDUCATION Albinism: epidemiology, genetics, cutaneous ଝ,ଝଝ characterization, psychosocial factors a,∗ b Carolina Reato Marc¸on , Marcus Maia a Pro-Albino Program Dermatology Clinic, Department of Medicine, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil b Department of Oncology Dermatology Clinic, School of Medical Sciences, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil Received 14 April 2019; accepted 9 September 2019 Available online 30 September 2019 Abstract Oculocutaneous albinism is an autosomal recessive disease caused by the complete KEYWORDS absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence Albinism; of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and Albinism, are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the oculocutaneous; world, albinism remains a little known disorder, both in relation to epidemiological data and to Keratosis, actinic; phenotypic and genotypic variation. In several regions of the country, individuals with albinism Sunscreening agents; have no access to resources or specialized medical care, and are often neglected and deprived Skin neoplasms; of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during Social stigma the year nationwide. Consequently, actinic damage and skin cancer occur early and have a high incidence in this population, often leading to premature death. Skin monitoring of these patients and immediate therapeutic interventions have a positive impact in reducing the morbidity and mortality associated with this condition. Health education is important to inform albinos and their families, the general population, educators, medical professionals, and public agencies about the particularities of this genetic condition. The aim of this article is to present a review of the epidemiological, clinical, genetic, and psychosocial characteristics of albinism, with a focus in skin changes caused by this rare pigmentation disorder. © 2019 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana,˜ S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). ଝ How to cite this article: Marc¸on CR, Maia M. Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors. An Bras Dermatol. 2019;94:503---20. ଝଝ Study conducted at the Albinism Outpatient Clinic, Clinic of Dermatology, Department of Medicine, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil. ∗ Corresponding author. E-mail: [email protected] (C.R. Marc¸on). https://doi.org/10.1016/j.abd.2019.09.023 0365-0596/© 2019 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana,˜ S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 504 Marc¸on CR, Maia M Introduction To date, 19 genes have been linked to the different clinical presentations of albinism, including seven for OCA. Four main types of non-syndromic albinism were initially Etiology, definition, and clinical condition described: from OCA Type 1 (A and B) to OCA4. The OCA1A type is the most severe, with a total absence of melanin pro- Oculocutaneous albinism (OCA) is an autosomal recessive duction throughout life, whereas the other forms --- OCA1B, disorder caused by the complete absence or reduction OCA2, OCA3, and OCA4 --- exhibit some accumulation of of biosynthesis of melanin in melanocytes. Patients with pigments over time. Mutations in the TYR, OCA2, TYRP1, albinism have a normal number of melanocytes in the epi- and SLC45A2 genes are the main cause of oculocutaneous dermis and follicles, but the melanin pigment is totally or 2,5,10 1 --- 4 albinism. Recently, another two new genes, SLC24A5 partially absent. Individuals with oculocutaneous albinism 20 and C10orf11, have been identified as responsible for caus- are unable to oxidize tyrosine into dopa through tyrosinase. ing OCA6 and OCA7, respectively, giving a total of seven This inability to produce pigment causes pale complexion, different types of albinism. A locus was also mapped in the white or fair hair, and red eyes, as light reflects blood ves- region of the human chromosome 4q24, the genetic cause sels in the retina, or greenish-blue or light brown eyes, if 21 of OCA5. there is pigment formation in the iris. In fact, the pheno- However, there remain a substantial number of albinism typic variability of albinism is broad, ranging from complete cases without molecular identification, suggesting that more absence of pigmentation of the hair, skin, and eyes to mild 5 --- 7 genes are associated with the condition. In addition, the depigmentation (Figs. 1 --- 3 ). lack of knowledge of the underlying mechanisms by which a Due to the reduction or absence of melanin, albinos are genetic mutation induces a deleterious functional effect on highly susceptible to the harmful effects of ultraviolet (UV) 5,8,9 the gene’s product implies that the disorder cannot yet be radiation and are at greater risk of actinic damage. Clin- 21 fully understood. ical management should include education of albinos and In Brazil, albinism is clinically diagnosed based on the family members on the importance of preventing sun expo- presence of typical cutaneous abnormalities and ocular sure and about methods to protect against UV radiation. findings. The distinction between albinism subtypes based Many albinos develop actinic keratosis or skin cancers 5,8---12 on clinical characteristics and the broad phenotypic het- before reaching the age of 30 years. The sequelae of erogeneity of the disorder hinders the establishment of skin cancer are among the leading causes of early death 11,12 phenotypic and genetic correlations, and there is exten- in albino patients. Skin cancer occurs in young adults sive overlapping of different forms of the disease. Molecular among albino patients with non-photoprotected exposure studies to define the exact type of mutation are therefore to sun. In those patients, skin cancer is invariably multiple necessary. However, this test is currently not available under and biologically aggressive in nature, although melanoma is 2 --- 4 5,8,9 the Brazilian public health system. rare. The cancer typically occurs on the head or neck, Albinism is a genetic disorder that affects individuals of areas usually more exposed to solar radiation. Given their all social classes and countries worldwide, albeit at differ- high sensitivity to UV light, albinos need total sun protection ent prevalence rates. The global incidence of albinism is and should undergo regular skin exams every six months or 5,8,9 1:20,000 individuals, with a lower rate in the United States less. 1,7,22 (1:37,000), while the highest rate reported in the lit- Reduced visual acuity, refractive errors, iris translucency, erature to date is amongst the Cuna indigenous people (in nystagmus, foveal hypoplasia, fundus hypopigmentation, Panama and Colombia), who have an estimated incidence and abnormal decussation of optic nerve fibers at the chiasm 23 of 6.3 per 1000 population. High rates have also been are also common features in albinos. This misrouting is cha- 22,23 24 reported in Africa. In Tanzania, Luande et al. estimated racterized by excessive crossing of fibers at the optic chiasm, there were 700 albinos living in Dar es Salaam, represent- which can result in strabismus and reduced stereoscopic ing a prevalence of 1:1500. In sub-Saharan Africa, 1:5000 vision. In addition, photophobia may be severe. Albinos are 25 to 1:15,000 are affected by albinism. A review study pub- also ocularly more susceptible to the harmful effects of UV 5 --- 7 lished in 2006 revealed that seven publications contained radiation and most individuals with albinism have some epidemiological data on the prevalence of albinism in South degree of low visual acuity. 26 Africa, Zimbabwe, Tanzania, and Nigeria. The prevalence of albinism in these studies ranged from 1:15,000 in the mid- 27 Albinism types and epidemiology eastern state of Nigeria to 1:1000 among the Tonga tribe of 28 Zimbabwe, an isolated rural community. Albinism is con- Albinism can occur in syndromic and non-syndromic forms. sidered a relatively common hereditary condition among In syndromic forms of albinism such as the Hermansky- populations of South Africa. Besides the limited geographical Pudlak and Chediak-Higashi subtypes, hypopigmentation mobility, consanguinity, together with other traditional mar- and visual impairments coexist with more severe pathologi- riage practices, may also be pertinent factors in assessments 22,27---29 cal abnormalities. Hermansky-Pudlak syndrome can present of current and future trends of albinism prevalence. with immunological changes, interstitial pulmonary fibrosis, The frequency of different types of OCA differs according granulomatous colitis, and hemorrhagic diathesis secondary to the population. OCA1 is the most commonly found subtype 30,31 to platelet alterations. Chediak-Higashi syndrome, besides in Caucasians, accounting for 50% of all cases worldwide. hypopigmentation, can manifest with hematologic changes, OCA2, or brown OCA, is responsible for 30% of cases world- high susceptibility to infections, bleeding, and neurologi- wide and is more common in Africa, where it affects an 13---17 cal problems. Albinism can also be expressed by the estimated 1:10,000 and more than 1:1000 among certain 5,18,19 27,32 exclusively ocular form (OA1 and FHONDA syndrome). populations. This is largely due to a highly frequent Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors 505 Figure 1 Phenotype in albinism. Wide phenotypic variability among children with albinism. Figure 2 Phenotype in albinism. Wide phenotypic variability among women with albinism. 32---35 deletion of OCA2 found in the African population. OCA3, every four people affected by OCA. In Japan and China, 31,36 or red OCA, is practically nonexistent in Caucasians, but the predominant form is OCA1, followed by OCA4.