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Ocular albinism, type II(AIED)

MedGen UID:
120643
Concept ID:
C0268505
Disease or Syndrome
Synonyms: AIED; Aland island eye disease; Forsius Eriksson type ocular albinism
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): CACNA1F (Xp11.23)
 
Monarch Initiative: MONDO:0010371
OMIM®: 300600
Orphanet: ORPHA178333

Definition

Aland Island eye disease (AIED) is an X-linked recessive retinal disease characterized by fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect (303900), progressive myopia, and defective dark adaptation. Although AIED has been referred to as a form of albinism, there is no misrouting of the optic nerves, which excludes it from the formal diagnosis of classic albinism (King et al., 2001). [from OMIM]

Additional description

From MedlinePlus Genetics
Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.

The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss.

Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.

Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.  https://medlineplus.gov/genetics/condition/ocular-albinism

Clinical features

From HPO
Giant melanosomes in melanocytes
MedGen UID:
812551
Concept ID:
C3806221
Finding
The presence of large spherical melanosomes (1 to 6 micrometer in diameter) in the cytoplasm of melanocytes.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Hypopigmentation of the fundus
MedGen UID:
101805
Concept ID:
C0151891
Disease or Syndrome
Reduced pigmentation of the fundus, typically generalized. Fundoscopy may reveal a low level pigment in both RPE and choroid with clear visibility of choroidal vessels (pale/albinoid) or low pigment level in the RPE with deep pigment in choroid so that visible choroidal vessels are separated by deeply pigmented zones (tesselated/tigroid).
Severely reduced visual acuity
MedGen UID:
226987
Concept ID:
C1301509
Disease or Syndrome
Severe reduction of the ability to see. On the 6m visual acuity scale, severe reduction is defined as less than 6/60 but at least 3/60. On the 20ft visual acuity scale, severe reduction is defined as less than 20/200 but at least 20/400. On the decimal visual acuity scale, severe reduction is defined as less than 0.1 but at least 0.05.
Foveal hypoplasia
MedGen UID:
393047
Concept ID:
C2673946
Finding
Underdevelopment of the fovea centralis.
Protanopia
MedGen UID:
1635279
Concept ID:
C4551767
Disease or Syndrome
Blue and green cones only; no functional red cones.

Professional guidelines

PubMed

White D, Rabago-Smith M
J Hum Genet 2011 Jan;56(1):5-7. Epub 2010 Oct 14 doi: 10.1038/jhg.2010.126. PMID: 20944644

Recent clinical studies

Etiology

Wong EWN, Cheng SSW, Woo TTY, Lam RF, Lai FHP
Ophthalmic Genet 2023 Aug;44(4):403-407. Epub 2022 Nov 4 doi: 10.1080/13816810.2022.2135107. PMID: 36330599
Mauri L, Barone L, Al Oum M, Del Longo A, Piozzi E, Manfredini E, Stanzial F, Benedicenti F, Penco S, Patrosso MC
Gene 2014 Jan 1;533(1):398-402. Epub 2013 Oct 3 doi: 10.1016/j.gene.2013.09.053. PMID: 24096233
Grønskov K, Ek J, Brondum-Nielsen K
Orphanet J Rare Dis 2007 Nov 2;2:43. doi: 10.1186/1750-1172-2-43. PMID: 17980020Free PMC Article
Spritz RA
Hum Mol Genet 1994;3 Spec No:1469-75. doi: 10.1093/hmg/3.suppl_1.1469. PMID: 7849740

Diagnosis

Wong EWN, Cheng SSW, Woo TTY, Lam RF, Lai FHP
Ophthalmic Genet 2023 Aug;44(4):403-407. Epub 2022 Nov 4 doi: 10.1080/13816810.2022.2135107. PMID: 36330599
Mauri L, Barone L, Al Oum M, Del Longo A, Piozzi E, Manfredini E, Stanzial F, Benedicenti F, Penco S, Patrosso MC
Gene 2014 Jan 1;533(1):398-402. Epub 2013 Oct 3 doi: 10.1016/j.gene.2013.09.053. PMID: 24096233
Chiang PW, Spector E, McGregor TL
Am J Med Genet A 2009 Dec;149A(12):2739-44. doi: 10.1002/ajmg.a.33128. PMID: 19938076
Grønskov K, Ek J, Brondum-Nielsen K
Orphanet J Rare Dis 2007 Nov 2;2:43. doi: 10.1186/1750-1172-2-43. PMID: 17980020Free PMC Article
Spritz RA
Hum Mol Genet 1994;3 Spec No:1469-75. doi: 10.1093/hmg/3.suppl_1.1469. PMID: 7849740

Prognosis

Wong EWN, Cheng SSW, Woo TTY, Lam RF, Lai FHP
Ophthalmic Genet 2023 Aug;44(4):403-407. Epub 2022 Nov 4 doi: 10.1080/13816810.2022.2135107. PMID: 36330599
Rimoldi V, Straniero L, Asselta R, Mauri L, Manfredini E, Penco S, Gesu GP, Del Longo A, Piozzi E, Soldà G, Primignani P
Gene 2014 Mar 1;537(1):79-84. Epub 2013 Dec 18 doi: 10.1016/j.gene.2013.11.102. PMID: 24361966

Clinical prediction guides

Rimoldi V, Straniero L, Asselta R, Mauri L, Manfredini E, Penco S, Gesu GP, Del Longo A, Piozzi E, Soldà G, Primignani P
Gene 2014 Mar 1;537(1):79-84. Epub 2013 Dec 18 doi: 10.1016/j.gene.2013.11.102. PMID: 24361966
White D, Rabago-Smith M
J Hum Genet 2011 Jan;56(1):5-7. Epub 2010 Oct 14 doi: 10.1038/jhg.2010.126. PMID: 20944644

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