iris transillumination

Anterior Segment Dysgenesis 6

Clinical Characteristics
Ocular Features: 

This is a congenital anterior segment dysplasia syndrome.  Iris hypoplasia with transillumination, corectopia, iridodenesis, and iridocorneal adhesions can be seen.  Increased intraocular pressure is a risk and ectopia lentis is often present.  Peters anomaly and defects in all layers of the cornea may be present.

No foveal hypoplasia is present.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

A single male patient of native American/French Canadian background has been reported with compound heterozygous mutations in the CYP1B1 gene (2p22.2).

See Anterior Chamber Dysgenesis 8 for another autosomal recessive disorder with somewhat similar clinical features.  Three families with 4 affected individuals have been reported with homozygous or compound heterozygous mutations in the CPAMD8 gene (19p13.11).

The genes FOXE3 and PAX6 are characterized as transcription factors and play important roles in ocular development.  However, while mutations in these are frequently found in patients with dysgenesis of the anterior chamber they often cause more widespread ocular and systemic anomalies (e.g., Gillespie syndrome [206700]).  Therefore in this database the anterior chamber constellations of anomalies associated with mutations in these genes are not considered to be simplex conditions.

See also related disorders iridogoniodysgenesis type 1 (601631) and type 2 (137600), and anterior segment mesenchymal dysgenesis (107250).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Lifelong pressure monitoring is important.

References
Article Title: 

Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly

Vincent A, Billingsley G, Priston M, Williams-Lyn D, Sutherland J, Glaser T, Oliver E, Walter MA, Heathcote G, Levin A, Heon E. Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly. J Med Genet. 2001 May;38(5):324-6. PubMed PMID: 11403040; PubMed Central PMCID: PMC1734880.

PubMed ID: 
11403040

Anterior Segment Dysgenesis 8

Clinical Characteristics
Ocular Features: 

This is a congenital anterior segment dysplasia syndrome with considerable clinical heterogeneity.  Iris hypoplasia with transillumination, corectopia, iridodenesis, and iridocorneal adhesions are often seen.  Intraocular pressure may be elevated in older individuals.  Ectopia lentis is often present.  Lenticular opacities consisting primarily of posterior cortical opacification are common.  Visual acuity varies from 6/6 to 6/24.

No foveal hypoplasia is present but one of four reported patients was described with bilateral optic nerve dysplasia.     

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

Three families with 4 affected individuals with similar clinical features have been reported with homozygous or compound heterozygous mutations in the CPAMD8 gene (19p13.11).

A single male patient of native American/French Canadian background with somewhat similar clinical features has been reported with compound heterozygous mutations in the CYP1B1 gene (2p22.2) but this is likely a unique condition (Anterior Segment Dysgenesis 6).

The genes FOXE3 and PAX6 are characterized as transcription factors and play important roles in ocular development.  However, while mutations in these are frequently found in patients with dysgenesis of the anterior chamber they often cause more widespread ocular and systemic anomalies (e.g., Gillespie syndrome [206700]).  Therefore in this database the anterior chamber constellations of anomalies associated with mutations in these genes are not considered to be simplex conditions. 

See also related disorders iridogoniodysgenesis type 1 (601631) and type 2 (137600), and anterior segment mesenchymal dysgenesis (107250).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Several patients have had cataract surgery.  Monitoring intraocular pressure throughout life is necessary and prompt treatment for glaucoma is important.

References
Article Title: 

Albinism, Oculocutaneous, Type V

Clinical Characteristics
Ocular Features: 

The phenotype in the two families studied includes photophobia, nystagmus, foveal hypoplasia and decreased visual acuity.  The fundus is hypopigmented.

Systemic Features: 

The hair is golden-colored and the skin is described as white. 

Genetics

The specific gene causing this form of oculocutaneous albinism has not been identified.  However, an area of homozygosity in the region of 4q24 has been identified in 6 members in two families belonging to a large consanguineous Pakistani pedigree in which it segregates with the OCA5 phenotype. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for oculocutaneous albinism but appropriately tinted glasses could be beneficial.

References
Article Title: 

Increasing the complexity: new genes and new types of albinism

Montoliu L, Gronskov K, Wei AH, Martinez-Garcia M, Fernandez A, Arveiler B, Morice-Picard F, Riazuddin S, Suzuki T, Ahmed ZM, Rosenberg T, Li W. Increasing the complexity: new genes and new types of albinism. Pigment Cell Melanoma Res. 2014 Jan;27(1):11-18. Review.

PubMed ID: 
24066960

Albinism, Oculocutaneous, Type VII

Clinical Characteristics
Ocular Features: 

Nystagmus and iris transillumination are present in all family members studied.  VEP studies show asymmetric decussation of axons in the chiasm.  The peripheral retina may have striking hypopigmentation. OCT reveals hypoplasia of the foveal region.   Photophobia is not a significant problem. Visual acuity is mildly to moderately reduced.

Systemic Features: 

Homozygous individuals are lighter in complexion than other family members. Hair color ranges from pale blond to dark brown.

Genetics

Homozygous mutations in the C10orf11 gene (10q22.2-q22.3) are responsible for the phenotype of this autosomal recessive condition.  The gene is active in melanocyte differentiation.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment for the hypopigmentation has been reported.  Visual function might be improved with low vision aids.

References
Article Title: 

Increasing the complexity: new genes and new types of albinism

Montoliu L, Gronskov K, Wei AH, Martinez-Garcia M, Fernandez A, Arveiler B, Morice-Picard F, Riazuddin S, Suzuki T, Ahmed ZM, Rosenberg T, Li W. Increasing the complexity: new genes and new types of albinism. Pigment Cell Melanoma Res. 2014 Jan;27(1):11-18. Review.

PubMed ID: 
24066960

Albinism, Oculocutaneous, Type VI

Clinical Characteristics
Ocular Features: 

Nystagmus is usually present from birth and visual acuity is in the range of 20/100.  There is marked hypopigmentation in the retina and the iris often transilluminates.  OCT usually shows foveal flattening consistent with hypoplasia.  Most patients experience severe photophobia and many have strabismus.

Systemic Features: 

There is usually complete loss or a severe reduction of melanin in skin, hair, and eyes.  Hair color is blond but may become tinged with brown in older individuals.  The skin may have pigmented nevi and has a tendency to tan in some patients.

Genetics

This is an autosomal recessive disorder resulting from mutations in SLC24A5 (15q21.1).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is available.  Visual function can be improved with low vision aids.

References
Article Title: 

SLC24A5 Mutations are Associated with Non-Syndromic Oculocutaneous Albinism

Morice-Picard F, Lasseaux E, Fran?ssois S, Simon D, Rooryck C, Bieth E, Colin E, Bonneau D, Journel H, Walraedt S, Leroy BP, Meire F, Lacombe D, Arveiler B. SLC24A5 Mutations are Associated with Non-Syndromic Oculocutaneous Albinism. J Invest Dermatol. 2013 Aug 28. [Epub ahead of print] PubMed PMID: 23985994.

PubMed ID: 
23985994

Microcoria, Congenital

Clinical Characteristics
Ocular Features: 

This disorder is a type of anterior chamber dysgenesis since the pupil and iris anomalies are associated with goniodysgenesis (prominent iris processes and high iris root insertion) and glaucoma.  The dilator muscle of the iris is hypoplastic and even topical mydriatics have little impact on pupil size. The pupil has a mean diameter of 0.8 mm and only dilates to a mean size of 1.4 mm.  The iris stroma is also hypoplastic and often lacks crypts and collarettes.  Transillumination defects of the iris are consistently present.  Axial myopia is a feature in some families (83% of affected individuals have refractive errors in the range of -10D) and seems to be progressive .  Juvenile glaucoma is frequently present (at least 30% require treatment) and is usually detected in the second (20%) through fourth decades of life.  All patients with glaucoma have evidence of 'trabeculodysgenesis' but the same features may also be seen in some patients without glaucoma.  The intraocular pressure is difficult to control pharmacologically.  Visual acuity varies widely but no retinal changes have been described.

Ultrastructural studies show lack of myofilaments and desmin in the stromal cytoplasmic processes of the anterior pigmented cells of the iris suggesting failure of full development of the pupil dilator muscle cells.

Systemic Features: 

There are no systemic abnormalities in this condition.

Genetics

This is an autosomal dominant disorder secondary to a mutation located at 13q13-q32.  The specific mutation responsible has not been identified but a large deletion at 13q32.1 in one patient has been reported. 

Congenital microcoria is also a feature of autosomal recessive Pierson syndrome (609049) caused by homozygous mutations in the LAMB2 gene.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Glaucoma often requires surgery for control of intraocular pressure.

References
Article Title: 

Submicroscopic deletions at 13q32.1 cause congenital microcoria

Fares-Taie L, Gerber S, Tawara A, Ramirez-Miranda A, Douet JY, Verdin H, Guilloux A, Zenteno JC, Kondo H, Moisset H, Passet B, Yamamoto K, Iwai M, Tanaka T, Nakamura Y, Kimura W, Bole-Feysot C, Vilotte M, Odent S, Vilotte JL, Munnich A, Regnier A, Chassaing N, De Baere E, Raymond-Letron I, Kaplan J, Calvas P, Roche O, Rozet JM. Submicroscopic deletions at 13q32.1 cause congenital microcoria. Am J Hum Genet. 2015 Apr 2;96(4):631-9.

PubMed ID: 
25772937

Albinism, Oculocutaneous, Type III

Clinical Characteristics
Ocular Features: 

The irides may be multicolored with the central potion light brown and the peripheral areas blue-gray.  Translucency of a punctate and radial nature is present.  Nystagmus is present in almost all cases and strabismus is present in nearly half.  Visual acuity is in the range of 20/60 to 20/200.   Photophobia is less severe than in other types of oculocutaneous albinism, possibly because the vast majority of individuals (86%) have some pigmentation in the fundus. 

Systemic Features: 

The hair in dark-skinned people may be medium brown while the skin is often light brown and subject to faint tanning.  However, the hair is often copper-red in color which has given rise to the designation rufous oculocutaneous albinism. 

Genetics

This tyrosinase-positive type of albinism is sometimes called 'rufous' (ROCA) or 'brown' (BOCA) oculocutaneous albinism and is frequently found in dark-skinned individual such as Africans, African-Americans, and Hispanics.  Like other types it is inherited in an autosomal recessive pattern.  Mutations in the tyrosinase-related protein-1, TYRP1 (9p23), are responsible which seems to lead to an arrest in melanin maturation and a decrease in the amount of insoluble melanin in melanocytes.

Other autosomal recessive types of oculocutaneous albinism are: OCA1 (203100, 606952), OCA2 (203200), and OCA4 (606574). 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for the hypopigmentation.  However, precautions against excessive sun exposure are advised.  Low vision aids can be helpful. 

References
Article Title: 

Oculocutaneous albinism

Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov 2;2:43. Review.

PubMed ID: 
17980020

Albinism, Oculocutaneous, Type II

Clinical Characteristics
Ocular Features: 

The iris and retina lack normal pigmentation and translucency of the iris can be demonstrated.  Anomalous decussation of neuronal axons in the chiasm and foveal hypoplasia result in decreased visual acuity.  Vision loss into the range of 20/100-20/200 does not progress after early childhood but is sometimes as good as 20/30.   Nystagmus is often present from about 3-4 months of age although it is less severe than in type I oculocutaneous albinism (203100, 606952).  The iris may darken to some extent with age.  Strabismus has been reported.  Significant refractive errors are often present and stereopsis is reduced.  The VEP responses are altered and can be used to document abnormal chiasmal decussation. 

Systemic Features: 

Melanin pigment is reduced in the skin and hair as well as the eyes.  Individuals at birth may be misdiagnosed as OCA type I but it is common for pigmentation to increase in older individuals resulting in yellow or reddish-blond hair and the appearance of freckles and nevi.  The skin may be creamy-white but this is often not as striking as in OCAI.  It is possible for tanning to take place in some patients.  This condition in Africans or African Americans is sometimes called brown oculocutaneous albinism (BOCA).  There is an increased risk of skin cancer of all types. 

Genetics

Type II is the most common type of oculocutaneous albinism and is especially prevalent among individuals of African heritage and in several Native American populations.  It is an autosomal recessive condition caused by homozygous 2.7 kb deletions in the OCA2 gene (15q24.3-q12).  Heterozygotes have normal pigmentation. 

Oculocutaneous albinism type I (203100, 606952) is a separate disorder with many similar features caused by mutations in the TYR gene.  Other types of autosomal recessive albinism are OCA3 (203290 ), and OCA4 (606574). 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for the hypopigmentation.  Low vision aids can be helpful. Significant refractive errors should, of course, be corrected and dark lenses may be helpful during outdoor activities. The skin should be protected from excessive sun exposure. 

References
Article Title: 

Vision in albinism

Summers CG. Vision in albinism. Trans Am Ophthalmol Soc. 1996;94:1095-155.

PubMed ID: 
8981720

Oculocutaneous albinism

Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov 2;2:43. Review.

PubMed ID: 
17980020

Hermansky-Pudlak Syndrome

Clinical Characteristics
Ocular Features: 

Oculocutaneous hypopigmentation is common to all types of HPS.  The ocular manifestations are similar to that of other types of albinism.  Iris transillumination defects, nystagmus, and strabismus are common features.   Visual acuity is usually stable in the range of 20/40-20/300 and often accompanied by photophobia.  Foveal hypoplasia and fundus hypopigmentation are present similar to that found in other hypopigmentation disorders.  The same is true of excessive decussation of retinal neuron axons at the chiasm.  Many patients have significant refractive errors. 

Systemic Features: 

In addition to decreased hair, ocular, and skin pigmentation, HPS patients suffer from bleeding diathesis, platelet deficiencies, and accumulation of ceroid material in lysosomes.  Pigment can be found in large amounts in reticuloendothelial cells and in the walls of small blood vessels.  Some of the same features are found in Chediak-Higashi  syndrome (214500) which, however, has additional qualitative changes in leukocytes.   HPS2 differs from other forms of HPS in having immunodeficiency and congenital neutropenia.  Some patients, especially those with HPS1 and HPS4 mutations, have restrictive lung disease secondary to pulmonary fibrosis often causing symptoms in the third and fourth decades of life.  Others have granulomatous colitis, kidney failure, and cardiomyopathy.  Solar skin damage is a risk, including actinic keratosis, nevi, lentigines and basal cell carcinoma.

Bleeding time is prolonged secondary to an impairment of the normal aggregation response of platelets.  Easy bruising, epistaxis, prolonged bleeding during menstruation, after tooth extraction, and after minor surgical procedures are often reported.  Platelets lack the normal number of 'dense bodies'.  Coagulation factor activity and platelet counts are normal.

The amount of hair and skin pigmentation is highly variable.  Some patients are so lightly pigmented that they are misdiagnosed as having tyrosinase-negative albinism while others have yellow to brown hair with irides blue to hazel.  Some darkening of hair is common. 

Genetics

This is an autosomal recessive genetically heterogeneous condition resulting from mutations in at least 12 loci: HPS1 (203300) at 10q23.1-q23.2, AP3B1 causing HPS2 (608233) at 5q14.1, and AP3D1 (617050) whereas in types HPS3 (606118) at 3q24, HPS4 (606682) at 22q11.2-q12.2, HPS5 (607521) at 11p15-p13, HPS6 (607522) at 10q24.32 the mutations themselves have not been characterized.  HPS7 is caused by mutations in the DTNBP1 gene (607145) located at locus 6p22.3 and HPS8 by mutations in the BLOC1S3 gene (609762) at 19q13.  The nature of the mutations is variable and often unique to the population in which they are found. 

Chediak-Higashi  syndrome (214500) is a somewhat similar disorder but with leukocyte abnormalities and results from a different gene mutation.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

It has been suggested that any patients with pigmentation disorders should be asked about bleeding problems to rule out HPS.  A hematologic consultation should be obtained if necessary, especially before elective surgery, to avoid bleeding complications through the use of appropriate preoperative measures.   Low vision aids can be helpful.  The skin should be protected from sunburn.  Lifelong surveillance is required for ocular and systemic problems.  The use of aspirin and indomethacin should be avoided. 

References
Article Title: 

Mutations in AP3D1 associated with immunodeficiency and seizures define a new type of Hermansky-Pudlak syndrome

Ammann S, Schulz A, Krageloh-Mann I, Dieckmann NM, Niethammer K, Fuchs S, Eckl KM, Plank R, Werner R, Altmuller J, Thiele H, Nurnberg P, Bank J, Strauss A, von Bernuth H, Zur Stadt U, Grieve S, Griffiths GM, Lehmberg K, Hennies HC, Ehl S. Mutations in AP3D1 associated with immunodeficiency and seizures define a new type of Hermansky-Pudlak syndrome. Blood. 2016 Feb 25;127(8):997-1006.

PubMed ID: 
26744459

Albinism, Oculocutaneous, Type I

Clinical Characteristics
Ocular Features: 

Oculocutaneous albinism is a genetically and clinically heterogeneous condition.  It is congenital in origin and the combination of foveal hypoplasia and anomalous decussation of neuronal axons in the chiasm results in a permanent reduction of vision in the range of 20/50-20/200.  Most individuals have nystagmus, photophobia, and strabismus.  The iris usually is light blue and transmits light.  The retina lacks pigmentation as well.  The ocular features are similar in types IA and IB.  The iris may darken with age in type IB (606952 ). 

Systemic Features: 

There are generally no systemic abnormalities in these pigmentation disorders with the exception of sensorineural hearing loss in some, and, of course, complete absence of pigment in skin and hair.  Anomalous decussation of axons in the auditory system has been demonstrated in such cases and otic pigment is lacking in albinos.  The skin contains amelanic melanocytes but these cells contain granules similar to those of normal cells.   Some patients with residual tyrosinase activity (type 1B, 606952 ) develop some pigmentation of hair and skin, especially in cooler areas of the body such as the extremities. 

Genetics

This type of oculocutaneous albinism is caused by mutations in the TYR gene (11q14-q21) and inherited in an autosomal recessive pattern. 

Type IA (OCA1A) has no demonstrable tyrosinase activity while type IB (OCA1B, 606952) has a reduction in enzyme activity.  Yet other patients with mutations in TYR have a variant called 'yellow albinism' in which tyrosinase activity resembles that found in type IB.  To explain the difference in skin color, it has been suggested that an individual's background ethnicity may impact the pigmentation phenotype.

Other types also transmitted as autosomal recessive conditions are OCA2 (203200), OCA3 (203290), AND OCA4 (606574). 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no treatment for the basic disease but low vision aids may be helpful for some patients.  Dark glasses provide comfort for photophobic individuals.  The skin should be protected against sunburn. 

References
Article Title: 

A new hypothesis of OCA1B

Chiang PW, Drautz JM, Tsai AC, Spector E, Clericuzio CL. A new hypothesis of OCA1B. Am J Med Genet A. 2008 Nov 15;146A(22):2968-70.

PubMed ID: 
18925668

Oculocutaneous albinism

Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov 2;2:43. Review.

PubMed ID: 
17980020

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