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 myopia, hyperopia and oblique astigmatism. Abnormalities arising from optic dysfunctions include monocular vision and poor stereopsis. Hair and skin color are not necessarily pigmented in OA.

• 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]

• Chills

  Our district will cancel school if there is a Wind Chill Warning with sustained wind chills at a level of 35 degrees below zero or more. [oasd.org]

  Photo Credit Dolly Faibyshev for The New York Times Work Out and Chill? Cool temperature workouts may be the answer for those who want to exercise without becoming a hot mess. [nytimes.com]

• Surgical Procedure

  He works with severely obese people and creates a diet and exercise plan along with surgical procedures […] Continue Reading » Nipah Virus – {The Complete Guide} By Dr. [ihealthblogger.com]

• Strabismus

  The abnormal decussation of nerve fibers in OA is mainly responsible for causing strabismus. [symptoma.com]

  It was at the first appointment that he was diagnosed with Ocular Albinism, Strabismus (the turning in of his left eye) and Nystagmus. So many things… Read More [vips.org]

  […] along with a strong X-linked inheritance pattern in family members led to the diagnosis of X-linked ocular albinism, which is an uncommon condition that is characterized by congenital nystagmus, iris translucency, hypopigmentation of the ocular fundus, strabismus [ncbi.nlm.nih.gov]

  Strabismus (crossed eyes). Abnormal movements of the eye or head to compensate for the abnormality in the vision. [epainassist.com]

• Photophobia

  Refractive errors are treated with corrective glasses with tinted lenses recommended for the photophobia. Low vision aids and special education may be required. [disorders.eyes.arizona.edu]

  […] inheritance pattern in family members led to the diagnosis of X-linked ocular albinism, which is an uncommon condition that is characterized by congenital nystagmus, iris translucency, hypopigmentation of the ocular fundus, strabismus, foveal hypoplasia, photophobia [ncbi.nlm.nih.gov]

• Retinal Pigmentation

  The pattern of affection however represents a nonrandom embryological developmental pattern of the retinal pigment epithelium. [ncbi.nlm.nih.gov]

• Visual Impairment

  Even with glasses, most patients with albinism and ocular albinism are moderately to severely visually impaired. It is common for individuals with albinism to hold material close to read which can be very effective, but can lead to visual fatigue. [hopkinsmedicine.org]

  I hated crowds with a passion, but the only public place I felt safe was Disney… Read More Why this actor calls his visual impairment a “blessing” June 22, 2016 - By Jay Worthington Years ago, when I was starting out on my journey as a professional actor [blindnewworld.org]

  Visual aids, changing electronic font size, and special education for the visually impaired may be needed. Patients should wear hats/caps, clothing, and sunscreen on sun-exposed skin to prevent burning and skin cancer. [orpha.net]

• Visual Impairment

  Even with glasses, most patients with albinism and ocular albinism are moderately to severely visually impaired. It is common for individuals with albinism to hold material close to read which can be very effective, but can lead to visual fatigue. [hopkinsmedicine.org]

  I hated crowds with a passion, but the only public place I felt safe was Disney… Read More Why this actor calls his visual impairment a “blessing” June 22, 2016 - By Jay Worthington Years ago, when I was starting out on my journey as a professional actor [blindnewworld.org]

  Visual aids, changing electronic font size, and special education for the visually impaired may be needed. Patients should wear hats/caps, clothing, and sunscreen on sun-exposed skin to prevent burning and skin cancer. [orpha.net]

• Short Arm

  X-linked ichthyosis (steroid sulphatase deficiency) and X-linked ocular albinism have been mapped to the Xp22.3 region and cases have been reported with both conditions due to a partial short-arm deletion of the X chromosome. [ncbi.nlm.nih.gov]

  The subtracted cDNA clones enriched for eye/retina-specific messages will be selected for sequences encoded by the short arm of X-chromosome. The candidate genes will be identified by their map position. [grantome.com]

• Macula

  CONCLUSION: Female carriers of ocular albinism may manifest signs of retinal pigment epithelium mosaicism at the macula and the peripheral fundus. [ncbi.nlm.nih.gov]

  Fundus examination in the right eye showed a large type 5 choroidal coloboma involving complete disc, but sparing the macula [Figure 1] a. The left eye showed type 1 choroidal coloboma sparing both disc and macula [Figure 2] a. [ijo.in]

  A “tapetal-like” pattern of autofluorescence was visible at the macula in 3/6. Persistence of the inner retinal layers at the fovea was observed in 6/8 females. [journals.lww.com]

• Cutaneous Manifestation

  Other than being fair-skinned, the patient had no cutaneous manifestations of albinism, and pigmentation of body hair was intact. [nejm.org]

  Additionally, an X-linked form of ocular albinism leading to minor cutaneous manifestations in affected males also exists. [sema4.com]

• Hypopigmented Skin

  Some carriers have isolated patches of hypopigmented skin that does not tan to the same degree as uninvolved skin. [ncbi.nlm.nih.gov]

• Suggestibility

  Here, we present a second WS2 family with OA and provide evidence suggesting the TYR(R402Q) allele does not cause OA in this family. [ncbi.nlm.nih.gov]

• Nystagmus

  BACKGROUND: Nystagmus is common to all types of albinism. Some subjects with nystagmus lack convincing signs of albinism, have no other visual pathway disease, and are classified as possessing congenital idiopathic nystagmus (CN). [ncbi.nlm.nih.gov]

• Pendular Nystagmus

  Video Horizontal Pendular Nystagmus. (00:21) A 32-year-old Hispanic woman with ocular albinism presented with a congenital horizontal pendular nystagmus (see video ). [nejm.org]

  Common ocular manifestations accompanying XLOA comprise foveal hypoplasia, pendular nystagmus, reduced visual acuity and strabismus. [symptoma.com]

  It starts as a large-amplitude, low-frequency pendular nystagmus, which parents sometimes interpret as an inability to fixate on objects. 3 The nystagmus often dampens over time and may even disappear later in childhood. 1 Stress, fatigue, illness and [reviewofophthalmology.com]

• Involuntary Movements

  movement of the eyes (nystagmus). [ihealthblogger.com]

  Patients have significantly reduced acuity, are often cross-eyed (a symptom that is called strabismus), have a refractive error and astigmatism, an involuntary movement of the eyes called nystagmus, and an increased sensitivity to light and glare called [steadyhealth.com]

  Still hurts their eyes), nystagmus - a rapid involuntary movement of the pupils, squints (strabismus), peripheral vision difficulties, and long-sightedness. The condition is a static one. It will not get worse with time, but nor will it get better. [londondegani.blogspot.com]

  People with albinism may have nystagmus (involuntary movement of the eyes), reduced depth perception, photophobia (very sensitive to light), problems tracking moving objects and be either long or short sighted. [albinismaustralia.org]

• Oscillopsia

  The patient reported no oscillopsia (the sensation that viewed objects are moving back and forth). She had bilateral iris transillumination and foveal hypoplasia, and her bilateral visual acuity was 20/200. [nejm.org]

  Oscillopsia where the patient experiences disturbed vision and perceives static objects as moving. Photophobia (extreme sensitivity to light). Strabismus (crossed eyes). [epainassist.com]

  Foveation dynamics and oscillopsia in latent/manifest latent nystagmus. Invest Ophthalmol Vis Sci 1993;34:1125. 54. Abadi RV, Scallan CJ. Waveform characteristics of manifest latent nystagmus. Invest Ophthalmol Vis Sci 2000;41:3805-17. 55. [meajo.org]

• Irritability

  Fecal transplant is used to treat gut infections and is now being studied as a treatment for obesity, urinary tract infections, irritable bowel syndrome and more. [nytimes.com]

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. 

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.

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.