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Anais Brasileiros de Dermatologia 2019Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or... (Review)
Review
Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the world, albinism remains a little known disorder, both in relation to epidemiological data and to phenotypic and genotypic variation. In several regions of the country, individuals with albinism have no access to resources or specialized medical care, and are often neglected and deprived of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during 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.
Topics: Albinism; Brazil; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Keratosis, Actinic; Male; Melanins; Prevalence; Risk Factors; Skin Neoplasms; Ultraviolet Rays
PubMed: 31777350
DOI: 10.1016/j.abd.2019.09.023 -
Progress in Retinal and Eye Research Nov 2022Albinism is a pigment disorder affecting eye, skin and/or hair. Patients usually have decreased melanin in affected tissues and suffer from severe visual abnormalities,... (Review)
Review
Albinism is a pigment disorder affecting eye, skin and/or hair. Patients usually have decreased melanin in affected tissues and suffer from severe visual abnormalities, including foveal hypoplasia and chiasmal misrouting. Combining our data with those of the literature, we propose a single functional genetic retinal signalling pathway that includes all 22 currently known human albinism disease genes. We hypothesise that defects affecting the genesis or function of different intra-cellular organelles, including melanosomes, cause syndromic forms of albinism (Hermansky-Pudlak (HPS) and Chediak-Higashi syndrome (CHS)). We put forward that specific melanosome impairments cause different forms of oculocutaneous albinism (OCA1-8). Further, we incorporate GPR143 that has been implicated in ocular albinism (OA1), characterised by a phenotype limited to the eye. Finally, we include the SLC38A8-associated disorder FHONDA that causes an even more restricted "albinism-related" ocular phenotype with foveal hypoplasia and chiasmal misrouting but without pigmentation defects. We propose the following retinal pigmentation pathway, with increasingly specific genetic and cellular defects causing an increasingly specific ocular phenotype: (HPS1-11/CHS: syndromic forms of albinism)-(OCA1-8: OCA)-(GPR143: OA1)-(SLC38A8: FHONDA). Beyond disease genes involvement, we also evaluate a range of (candidate) regulatory and signalling mechanisms affecting the activity of the pathway in retinal development, retinal pigmentation and albinism. We further suggest that the proposed pigmentation pathway is also involved in other retinal disorders, such as age-related macular degeneration. The hypotheses put forward in this report provide a framework for further systematic studies in albinism and melanin pigmentation disorders.
Topics: Humans; Melanins; Mutation; Albinism; Retina; Pigmentation
PubMed: 35729001
DOI: 10.1016/j.preteyeres.2022.101091 -
Orphanet Journal of Rare Diseases Nov 2007Oculocutaneous albinism (OCA) is a group of inherited disorders of melanin biosynthesis characterized by a generalized reduction in pigmentation of hair, skin and eyes.... (Review)
Review
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.
Topics: Albinism, Oculocutaneous; Diagnosis, Differential; Humans; Prevalence
PubMed: 17980020
DOI: 10.1186/1750-1172-2-43 -
The Journal of Investigative Dermatology Jun 2022
Topics: Albinism; Albinism, Oculocutaneous; Asian People; China; Cohort Studies; Humans; Mutation; Spectrum Analysis
PubMed: 34838614
DOI: 10.1016/j.jid.2021.11.014 -
Clinics in Chest Medicine Sep 2016Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly... (Review)
Review
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes, including HPS-1, HPS-2, and HPS-4. HPS pulmonary fibrosis shows many of the clinical, radiologic, and histologic features found in idiopathic pulmonary fibrosis, but occurs at a younger age. Despite knowledge of the underlying genetic defects, there are currently no definitive therapeutic or preventive approaches for HPS pulmonary fibrosis other than lung transplant.
Topics: Albinism; Albinism, Oculocutaneous; Arteriovenous Malformations; Blood Coagulation Disorders; Crohn Disease; Epistaxis; Gastrointestinal Diseases; Hemorrhagic Disorders; Hermanski-Pudlak Syndrome; Humans; Hypertension, Pulmonary; Intracranial Arteriovenous Malformations; Liver Diseases; Pulmonary Artery; Pulmonary Fibrosis; Pulmonary Veins; Telangiectasis
PubMed: 27514596
DOI: 10.1016/j.ccm.2016.04.012 -
Pigment Cell & Melanoma Research Sep 2019Non-syndromic oculocutaneous albinism (nsOCA) is a group of genetically heterogeneous autosomal recessive disorders with complete lack or decrease pigmentation in skin,...
Non-syndromic oculocutaneous albinism (nsOCA) is a group of genetically heterogeneous autosomal recessive disorders with complete lack or decrease pigmentation in skin, hair, and eyes. TYR, OCA2, TYRP1, SLC45A2, SLC24A5, and LRMDA were reported to cause OCA1-4 and OCA6-7, respectively. By sequencing all the known nsOCA genes in 114 unrelated Chinese nsOCA patients combined with In silico analyses, splicing assay, and classification of variants according to the standards and guidelines of American College of Medical Genetics and Genomics, we detected seventy-one different OCA-causing variants separately in TYR, OCA2, SLC45A2, and SLC24A5, including thirty-one novel variants (13 in TYR, 11 in OCA2, and 7 in SLC45A2). This study shows that OCA1 is the most common (75/114) and OCA2 ranks the second most common (16/114) in Chinese. 99 patients of our cohort were caused by variants of all the known nsOCA genes. Cutaneous phenotypes of OCA1, OCA2, and OCA4 patients were shown in this study. The second OCA6 case in China was identified here. These data expand the spectrum of OCA variants as well phenotype and facilitate clinical implement of Chinese OCA patients.
Topics: Albinism, Oculocutaneous; Asian People; Cohort Studies; Genetic Markers; Humans; Mutation; Phenotype
PubMed: 31077556
DOI: 10.1111/pcmr.12790 -
Journal of Optometry 2023To describe the prevalence and severity of photosensitivity in patients with albinism, and to compare with ocular features and how this correlated with use and choice of...
PURPOSE
To describe the prevalence and severity of photosensitivity in patients with albinism, and to compare with ocular features and how this correlated with use and choice of optical filters.
METHODS
Cross-sectional study on 81 participants with ocular or oculocutaneous albinism. An ophthalmic evaluation including visual acuity, contrast sensitivity and evaluation of iris translucency and fundus hypopigmentation was performed. Participants were offered optical rehabilitation with testing of a wide panel of filters. The associations between ocular characteristics, subjective photosensitivity complaints, and filter choice were evaluated.
RESULTS
Photosensitivity was rated as "some" to "worst imaginable" in 77.8% of participants. Severity of photosensitivity correlated significantly with fundus hypopigmentation (p = 0.04) but not with iris translucency (p = 0.14) and it was worse in those with poor visual acuity but there was no association between photosensitivity and contrast vision. Seventy-four new pairs of spectacles were prescribed in the study. All outdoor spectacles contained a filter, whereas 26.5% of new indoor spectacles did not. Relatively neutral filter colors (gray, brown or a combination of gray and brown with other colors) and low transmission were preferred.
DISCUSSION
Photosensitivity is common in albinism, but research targeting treatment is limited. Color and neutral filters with a low light transmission were preferred, with participants having a large number of spectacles, presumably to meet their needs in different situations.
Topics: Humans; Cross-Sectional Studies; Albinism; Albinism, Oculocutaneous; Vision, Ocular; Visual Acuity
PubMed: 36028395
DOI: 10.1016/j.optom.2022.07.002 -
Asia-Pacific Journal of Ophthalmology...
Topics: Humans; Albinism, Oculocutaneous; Mutation
PubMed: 35342184
DOI: 10.1097/APO.0000000000000506 -
The British Journal of Ophthalmology Mar 1990
Topics: Albinism; Humans; Optic Chiasm
PubMed: 2322506
DOI: 10.1136/bjo.74.3.130 -
Ophthalmology Jun 2022To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). (Observational Study)
Observational Study
PURPOSE
To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH).
DESIGN
Multicenter, observational study.
PARTICIPANTS
A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384).
METHODS
Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans.
MAIN OUTCOME MEASURES
Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA).
RESULTS
The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH.
CONCLUSIONS
We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.
Topics: Albinism; Albinism, Ocular; Albinism, Oculocutaneous; Color Vision Defects; Cytoskeletal Proteins; Fovea Centralis; Humans; Membrane Proteins; Vision Disorders
PubMed: 35157951
DOI: 10.1016/j.ophtha.2022.02.010