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Ocular Albinism

Ocular albinism(OA) is a hereditary disorder characterized by absence or reduced amount of melanin pigment in eyes. Several types of OA have been recognized. Nettleship-Falls (OA1) and Forsius-Eriksson (OA2) are among the rarest forms of OA. X-linked ocular albinism (XLOA) is a less rare type of OA in which genetic mutation occurs in the X chromosome. 


The clinical presentation of OA varies from patient to patient. The form of OA along with the patient's racial background widely influence disease manifestation. Patients with naturally darker skin pigment present with less severe signs compared to those with paler complexion. Female carriers mainly display minor signs and remain asymptomatic throughout their life. Since XLOA is a congenital disorder, typical signs are undoubtedly identified during infancy

Apart from obvious findings of reduced pigmentation of retina, iris and fovea, one of the most distinctive features of OA is foveal hypoplasia [5]. Presence of certain ophthalmoscopic findings that can help predict underdevelopment of fovea include absence of foveal reflex, lack of pigment in macula lutea, reduced foveal pigmentation, hypopigmentation of fundus and failure of retinal vessels to encircle fovea. Blurred vision in OA often occurs due to foveal hypoplasia. 

Photodysphoria and strabismus are among the other most common features that accompany OA. The form and intensity of each clinical finding varies widely among patients. In OA, estropic strabismus is commonly observed. The abnormal decussation of nerve fibers in OA is mainly responsible for causing strabismus. Other definite findings include lack or absence of stereoacuity, transillumination defects of iris and pendular nystagmus which typically develops in affected males during infancy and creates visual disturbances. Hearing disturbances are common specifically in XLOA. Visual acuity is reduced and usually lies between 20/40 to 20/400. Refractive errors accompanying OA include myopiahyperopia and oblique astigmatismAbnormalities arising from optic dysfunctions include monocular vision and poor stereopsis. Hair and skin color are not necessarily pigmented in OA.

Coarse Facial Features
  • We describe a boy with an interstitial deletion of 6(q13-q15) and include "coarse" facial features, upslanting palpebral fissures, thin vermilion border of the upper lip, elongated philtrum, developmental delay, and profound hypotonia.[ncbi.nlm.nih.gov]
  • We describe a 3-year-old male with severe hypotonia, developmental regression and progressive neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and dysmyelinating motor sensory neuropathy.[ncbi.nlm.nih.gov]
  • facial features, upslanting palpebral fissures, thin vermilion border of the upper lip, elongated philtrum, developmental delay, and profound hypotonia.[onlinelibrary.wiley.com]
Short Stature
  • Other clinical findings in the complex glycerol kinase deficiency (CGKD) patients are mental retardation, short stature, and hypogonadotropic hypogonadism.[ncbi.nlm.nih.gov]
  • The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX)[ncbi.nlm.nih.gov]
  • Using the Agilent HaloPlex Target Enrichment System and next-generation sequencing (NGS) on the Illumina MiSeq platform, we identified 518 variants after rigorous filtering. Many of these variants were corroborated by Sanger sequencing.[ncbi.nlm.nih.gov]
Prominent Nasal Root
  • A family had the following manifestations of Waardenburg's syndrome (WS): prominent nasal root, white forelock, premature graying of the hair, freckled pigmentation of pale skin, hypoplastic heterochromia irides, heterochromia of the ocular fundi, congenital[ncbi.nlm.nih.gov]


The presence of characteristic eye findings can help in establishing diagnosis of OA. In case of XLOA, family history plays a major role in detecting the disorder. Since OA is predominant in males, the female carriers present with mild signs. Presence of pendular nystagmus, transillumination defects of iris, foveal hypoplasia, reduced visual acuity and hypopigmentation of ocular fundus and skin are clear signs of OA. Visual changes are almost absent in carrier females. Definite diagnostic tests that can aid in confirming diagnosis of OA are described below.

A visual evoked potential (VEP) is one the most accurate diagnostic tests that helps in identifying diverging optic pathways by displaying asymmetric VEP results between the two eyes.  

Optical coherence tomography (OCT) is another diagnostic tool used to confirm one of the atypical forms of OA called oculocutaneous albinism [6] [7] and determining severity of the disorder [8]. The test recognizes the extent to which ocular fovea and iris illumination are affected by measuring them through a grading system [9]. 

Microscopic evaluation test of skin biopsy can easily help in visualizing the presence of abnormal macromelanosomes in keratinocytes and melanocytes of the suspected male patients as well as female carriers. 

The most precise diagnostic tool that rules out all other ocular disorders without necessitating performance of any other diagnostic tests is molecular genetic testing of GPR143 gene. The test detects mutation in the affected gene and is 90% effective in confirming diagnosis in the affected male patients. Once the diagnosis is confirmed by molecular testing, no additional tests are needed. 


Since OA is genetic, the disorder cannot be treated. However, it is possible to correct the ensuing ocular abnormalities by symptomatic management. 

All patients with OA aged 16 or less must undergo annual ophthalmologic examination whereas all above 16 should be examined every 2 years. 

Correction of vision and photodysphoria can be achieved by using visual aids such as special filter glasses and photochromic lenses. Use of telescope can be helpful in correcting severe visual impairment whereas use of bifocal lenses is beneficial in managing refractive errors. Misalignment and compromised peripheral visual fusion field defects resulting from strabismus can be corrected by surgical intervention. Furthermore, patients should be counseled about maintaining a correct head posture to prevent nystagmus. Peripheral retinal defects are often treated with cryopexy.

The presence of reduced melanin increases the risk of sunburn and the development of skin cancer. Patients should be advised to wear protective clothing, sunscreen and minimize sun exposure. 


XLOA is a non-progressive disease with no major consequences. However, reduced visual acuity can affect quality of life. With the exception of Type I oculocutaneous albinism, many cases have been reported to show improvement in visual acuity with time.


The only etiologic factor associated with XLOA is the inheritance of the mutated GPR143 gene through a defective X chromosome. If the mutated gene is carried by the father, all daughters will develop XLOA since GPR143 is a component of the X chromosome. However, all of his sons will have a normal set of genes. Alternatively, if the mother carries the mutated gene in one of the two X chromosomes and transmits the affected gene to her sons, all of them will develop XLOA while the daughters will remain carriers. 


XLOA mainly effects males because of its hereditary transmission through a X-chromosome carrying the mutated gene. The females usually act as carriers of the disease with no clinical manifestations. The prevalence of XLOA is reported to be 1 in 50,000. 

Sex distribution
Age distribution


As described earlier, XLOA occurs as a result of the mutation of the G-protein coupled receptor gene (GPR143) located on a X-chromosome. The gene is normally involved in encoding membrane glycoprotein in the pigment producing organelles, the melanosomes. In the presence of a mutated GPR143 gene the glycoprotein becomes non-functional and the melanosomes fail to produce and release melanin, causing the melanosomes to become abnormally enlarged. At this stage, the melanosomes are referred to as macromelanosomes that are seen on epidermal melanocytes and retinal epithelium. Skin macromelanosomes serve as an important diagnostic tool for XLOA [4]. 

The precise mechanism behind pathogenesis of XLOA remains unknown [4]. However, certain theories have found to be associated with manifestations of definite signs of the disorder. The retinal pigment is believed to play an important role in the development of fovea. The foveal hypoplasia may therefore result in the absence of retinal pigment. The decline in visual acuity in XLOA is also thought to result due to foveal hypoplasia. Moreover, anatomical disturbance in arrangement of optic nerve fibers is found to be linked to the appearance of strabismus


Genetic counseling should be considered in males and females affected with XLOA. An affected male will transmit the disorder to all daughters because of inheritance of XLOA in X-linked recessive manner. Therefore, all sons of the affected male will remain healthy. Similarly, carrier women in XLOA possess 50% chances of transmitting the mutated GPR143 gene to all their children, irrespective of their gender. Molecular genetic testing and carrier testing should be performed in high risk patients and in patients with a familial history of XLOA. 

In the presence of known familial mutation, prenatal testing of pregnant women should be performed using chorionic villus sampling or amniotic fluid test to detect any possible case of GPR143 transmission to the fetus. 

Regular examination of ophthalmologic function to detect possible development of ocular dysfunction is recommended in all patients with OA. Typically, the suggested frequency for examination is once a year in patients aged 16 or less and once in every two years in adults above 16 years of age. 


Ocular albinism (OA) is a rare, genetic disorder that essentially affects eyes and is associated with reduced pigmentation of iris causing visual dysfunction. Among the many recognized forms of OA, X-linked recessive ocular albinism (XLOA) also referred to as ocular albinism Type I (OA1) is the most common form. The condition mainly affects males who present with obvious signs while females are rarely impacted and show slight ocular manifestations. The characteristic clinical features of XLOA comprise hypopigmentation of ocular iris, foveal hypoplasia, pendular nystagmus, strabismus and reduced visual acuity which ranges from 20/40 to 20/400 [1] [2]. Some patients may develop sensorineural deafness after few years [3]. 

The majority of the patients affected with XLOA solely presents with ocular manifestations and typically does not have pigmentation defects in other organs. Rarely, the skin may present with minor hypopigmentation. In either case, the patients always possess a pale complexion compared to other members of their family [3]. Since the disorder is genetic, the visual defects present in XLOA are evident since birth. The condition remains consistent and in some cases, the visual defects may improve with ageing.  

The melanosomes in the eyes which are responsible for storing pigment are affected in XLOA. In the pathogenesis of XLOA, the G-protein coupled receptor 143 gene (GPR143 gene) responsible for regulation of melanosomes becomes mutated which leads to XLOA. Common ocular manifestations accompanying XLOA comprise foveal hypoplasia, pendular nystagmus, reduced visual acuity and strabismus. Skin and hair hypopigmentation is relatively uncommon although the affected individual will have paler skin compared to his/her normal siblings.

Diagnosis of OA is determined by typical ocular findings and familial history of the disorder. Definite diagnostic tests that help in confirmation of OA are molecular genetic testing for identification of GPR143 gene, visual evoked potential (VEP) test, optical coherence tomography (OCT) and microscopic evaluation of macromelanosomes on skin biopsy. Treatment is based on symptomatic management of ocular symptoms and preventing skin damage by avoiding sun exposure.

Patient Information

Ocular albinism (OA) is a genetic disorder which is inherited from parents or affected relatives by transmission of the aberrant gene to the offspring. OA is characterized by absence or reduced amount of melanin pigments in the eyes. Melanin pigment is normally responsible for giving color to eye structures. Absence of melanin is followed by presentation of several eye defects. In some forms of OA, hearing may also become impaired and rarely, skin and hair may become affected. 

X-linked ocular albinism (XLOA) is a type of OA in which the disorder is transmitted through a sex chromosome (i.e, X-chromosome). XLOA primarily affects males although affected females can carry the defective gene but do not present the disorder clinically.

Common clinical signs of OA include involuntary movement of eye balls (nystagmus), reduced pigment of different structures of eyes such as retina, iris and fovea, misalignment of eyes (strabismus), photosensitivity (photodysphoria), reduced visual acuity and several secondary visual defects. 

The presence of specific ocular findings along with evident family history of the disorder and certain eye tests help in establishing accurate diagnosis of OA. Genetic testing performed to identify the aberrant gene provides precise diagnosis in 90% of affected patients. Other tests include visual evoked potential (VEP), optical coherence tomography (OCT), skin biopsy and microscopic examination of skin samples.

Treatment is based on symptomatic management of eye defects that occur from OA. Visual correction is achieved by using dark glasses to improve vision and avoid photosensitivity. For deeper complications, surgery is indicated. In case of skin manifestations, patients are counseled to minimize sun exposure by wearing protective clothing and sunscreen. 



  1. Dijkstal JM, Cooley SS, Holleschau AM, King RA, Summers CG. Change in Visual Acuity in Albinism in the Early School Years. J Pediatr Ophthalmol Strabismus. 2011;1-6. 
  2. Merrill K, Hogue K, Downes S, et al. Reading acuity in albinism: evaluation with MNREAD charts. J AAPOS. 2011;15(1):29-32.
  3. Bassi MT, Schiaffino MV, Renieri A, et al. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat Genet. 1995;10(1):13-19.
  4. Schnur RE, Wick PA, Bailey C, et al. Phenotypic variability in X-linked ocular albinism: relationship to linkage genotypes. Am J Hum Genet. 1994;55(3):484-496.
  5. McCafferty BK, Wilk MA, McAllister JT, et al. Clinical Insights Into Foveal Morphology in Albinism. J Pediatr Ophthalmol Strabismus. 2015;52(3):167-172.
  6. Rossi S, Testa F, Gargiulo A, et al. The role of optical coherence tomography in an atypical case of oculocutaneous albinism: a case report. Case Rep Ophthalmol. 2012;3(1):113-117.
  7. Meyer CH, Lapolice DJ, Freedman SF. Foveal hypoplasia in oculocutaneous albinism demonstrated by optical coherence tomography. Am J Ophthalmol. 2002;133(3):409-410.
  8. Sheth V, Gottlob I, Mohammad S, et al. Diagnostic Potential of Iris Cross-sectional Imaging in Albinism Using Optical Coherence Tomography. Ophthalmology. 2013;120(10):2082-2090.
  9. Seo JH, Yu YS, Kim JH, et al. Correlation of visual acuity with foveal hypoplasia grading by optical coherence tomography in albinism. Ophthalmology. 2007 Aug;114(8):1547-1551.

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Last updated: 2019-07-11 21:51