Hereditary Malignant Melanoma and the Fammm Syndrome
Henry T. Lynch, Ramon M. Fusaro in Hereditary Malignant Melanoma, 2019
Albinism is a genetic spectrum of disease involving different aspects of the metabolism and distribution of melanin in the skin, hair, and eyes. The term albinism is limited to those congenital universal hypomelanoses that involve the skin and eye (oculocutaneous albinism [OCA]) and the eye alone (ocular albinism [OA]). There are ten types of OCA: (1) tyrosinase-negative (ty-neg) OCA, (2) tyrosinase-positive (ty-pos) OCA, (3) yellow mutant OCA (YMA) (4) plastinum OCA (pt-OCA), (5) Hermansky-Pudlak syndrome (HPS), (6) brown OCA (BA), (7) rufous OCA (RA), (8) Cross-McKusick-Breen syndrome (CMBS), (9) black locks-albinism-deafness syndrome (BADS), and (10) Chediak-Higashi syndrome. The cutaneous findings are an absence or decrease in melanin pigmentation of the skin and hair. The eyes show the same pigmentation changes, but in addition, there is nystagmus, photophobia, and decreased visual acuity. All of these are inherited in an autosomal recessive pattern. At the other end of the genetic spectrum of OCA are the dominant forms with cutaneous hypomelanoses: (1) autosomal dominant OCA and (2) oculocutaneous albinoidism. In addition, there is albinism limited to the eye — ocular albinism. The skin is usually normal in color. There are five types of ocular albinism with only ocular pigmentation abnormalities: (1) X-linked type (Nettleship or Vogt), (2) X-linked type (Forsius-Eriksson or Aland eye disease), (3) Winship type, (4) autosomal recessive ocular albinism, and (5) autosomal dominant ocular albinism.5
Oculocutaneous albinism
Electra Nicolaidou, Clio Dessinioti, Andreas D. Katsambas in Hypopigmentation, 2019
The two main affected organs in albinism are the skin and eyes. However, patients with ocular albinism may also have skin problems, while patients with cutaneous albinism show ocular findings quite often.7 The degree of hypo- and depigmentation varies widely between the different types of albinism based on the activity of tyrosinase. Patients with completely inactive tyrosinase are totally depigmented at birth with no melanin in irises and retina, leading to red reflex and severe ocular defects. Their hair is totally white, and they never get darker or tanned. If there is some degree of functional tyrosinase, it may lead to some hair color, seen in patients with the so-called OCA1-b form of albinism, where a mild degree of skin pigmentation may develop later in life. One extremely rare form of OCA1-B is the so-called “temperature-sensitive OCA1-b,” where tyrosinase is only active when the temperature is lower than the body temperature, resulting in some degree of peripheral pigmentation of the extremities.1,3,7
The Normativist Theory
Lawrie Reznek in The Nature of Disease, 1987
There is the following more serious objection. It might be argued that the condition of having black skin in a white racist society is something that makes those individuals worse off. But it would be wrong to say that the condition is a disease. We might try to avoid this by saying that the individual is not made worse off by his black skin but by the social prejudice acting on that trait. But individuals with albinism are also not made worse off by the fairness of their skins, but by the sun’s rays acting on that trait. And albinism is still a disease. Norman Daniels points this problem out: [W]e must specify the range of environments taken as ‘natural’ for the purpose of revealing dysfunction. The latter is critical to the second feature of the biomedical model: for example, what range of social roles and environments is included in the natural range? If we allow too much to the social environment, then racially discriminatory environments might make being of the wrong race a disease; if we disallow all socially created environments, then we seem not to be able to call dyslexia a disease (disability) (Daniel, 1981, p. 156).
A novel iris transillumination grading scale allowing flexible assessment with quantitative image analysis and visual matching
Published in Ophthalmic Genetics, 2018
Chen Wang, Flavia Brancusi, Zaheer M. Valivullah, Michael G. Anderson, Denise Cunningham, Adam Hedberg-Buenz, Bradley Power, Dimitre Simeonov, William A. Gahl, Wadih M. Zein, David R. Adams, Brian Brooks
Albinism is caused by a group of genetic disorders associated with reduced melanin pigment biosynthesis. Oculocutaneous albinism (OCA) results in decreased pigmentation in the hair, skin, and eyes. Most OCA is autosomal recessive and caused by one of four genes: TYR (OCA-1A and OCA-1B, MIM 203100), OCA2 (OCA-2, MIM 203200), TYRP1 (OCA-3, MIM 203290), and SLC45A2 (OCA-4, MIM 606574). Additional rare OCA genes have recently been reported.1–3 A separate group of rare conditions combine OCA-like albinism and involvement of nonpigmented tissues. Examples include the Hermansky–Pudlak syndrome (types 1–9) and Chediak–Higashi syndrome. Ocular albinism (GPR143, MIM 300500) is characterized by X-linked inheritance and hypopigmentation restricted principally to the eye. All types of OCA, as well as OA, are associated with variable nystagmus, foveal hypoplasia, retinal hypopigmentation, abnormal retinal axonal fiber decussation, and iris hypopigmentation. OCA has a substantial breadth of phenotypic heterogeneity confounding subtype diagnosis through phenotype evaluation alone.4 To date, treatment of albinism is largely supportive, including low-vision aids, correction of refractive errors, treatment of amblyopia, and extraocular muscle surgery for strabismus and/or anomalous head posture.
Clinical albinism score, presence of nystagmus and optic nerves defects are correlated with visual outcome in patients with oculocutaneous albinism
Published in Ophthalmic Genetics, 2021
Alina V. Dumitrescu, Johnny Tran, Wanda Pfeifer, Sajag V. Bhattarai, Andrew Kemerley, Taylor V. Dunn, Kai Wang, Tod E. Scheetz, Arlene Drack
Kruit et al. have previously proposed diagnostic criteria for patients with suspected OCA. Their criteria were developed and applied retrospectively to cohorts of mostly Caucasian/Danish patients. When applied retrospectively to our cohort, overall, 78% of our cases presented here met the Kruit et al. criteria. Of the 13 patients in our cohort who did not meet Kruit et al. criteria, all had at least 3 clinical criteria present and 10 of 13 would have met Kruit et al. criteria if their genetic testing were also positive. These patients may have a phenocopy of albinism, but it is also possible that their genetic testing was not complete. All of our 20 cases with complete, confirmatory albinism genotypes met the Kruit et al. criteria. Fifteen out of the 20 confirmed cases would have met the purely clinical criteria for diagnosis (3 major or 2 major and 2 minor features); however, 5 would have only been diagnosed based on their positive genetic testing. This means that the Kruit et al. criteria for diagnosis, when used without genetic testing may miss up to 25% of albinism cases. As Kruit et al. have noted in their paper, the severity of clinical features of albinism is variable and none of them is enough by itself to establish the diagnosis.
Genotype-phenotype associations in Danish patients with ocular and oculocutaneous albinism
Published in Ophthalmic Genetics, 2021
Line Kessel, Birgit Kjer, Ulrikke Lei, Morten Duno, Karen Grønskov
Albinism is a congenital condition characterized by hypopigmentation of eyes, skin and hair. Nystagmus, foveal maldevelopment and abnormal crossing of visual pathways, also called misrouting, are other common features of albinism. Albinism is a rare disease thought to affect 1 in 14,000 (1). Many patients with rare diseases struggle to get a diagnosis within an acceptable time frame (2). While it is not difficult to suspect albinism in typical cases such as an infant presenting with nystagmus and unpigmented skin, hair and eyes some patients with atypical presentations pose clinical challenges (3) and may be undetected. In addition, the phenotypic appearance may depend on the ethnic background of the study population (4,5) and the age of patients (6).
Related Knowledge Centers
- Absorption
- Biological Pigment
- Chlorophyll
- Oculocutaneous Albinism
- Photosynthesis
- Skin
- Melanin
- Iris
- Laboratory Animal Sources
- Structural Coloration