nystagmus

This type of oculocutaneous albinism is one of the more common types found among Japanese and maybe Chinese individuals although it has also been reported in German and Turkish individuals.  This is a rare autosomal recessive form of albinism caused by mutations in the MATP (SLC45A2) gene located at 5p13.3. 

A single Japanese family with 16 affected members has been reported in which the transmission pattern was consistent with autosomal dominant inheritance. Heterozygous mutations in the SLC45A2 gene segregated appropriately.

Other types include OCA1 (203100, 606952 ), OCA2 (203200 ), OAC3 (203290), OAC5 (615179), and OCA6 (113750)..

This is an autosomal recessive condition caused by mutations in the CNNM4 gene at 2q11.2. 

This is an autosomal recessive disorder resulting from homozygous mutations in the LAMB2 gene located at 3p21.  The normal gene encodes laminin beta-2 that is strongly expressed in intraocular muscles which may explain the hypoplasia of ciliary and pupillary muscles in Pierson syndrome.  Mutations in this gene are often associated with nephronophthisis but ocular abnormalities are not always present. 

Microcoria is also a feature of the autosomal dominant ocular condition known as congenital microcoria (156600).

This disorder is associated with mutations in the PAX6 gene (11p13) and inherited as an autosomal dominant.

The protein product of the PAX6 gene is a transcription factor that attaches to DNA and regulates the expression of other genes.  PAX6 plays a major role primarily in development of the eye and central nervous system but evidence suggests it is also active postnatally.  Hundreds of mutations have been found in disorders such as hereditary keratitis, aniridia, Peters anomaly, hypoplasia and colobomas of the optic nerve.  This database contains 8 conditions in which mutations in PAX6 seem to be responsible, including syndromal conditions such as Stromme and Gillespie syndromes in which there may be cognitive disabilities. 

True isolated foveal hypoplasia without lens or corneal disease does exist as well but this condition (FVH2) is not well defined.  Homozygous mutations in SLC38A8 have been found to cosegregate with this form of foveal hypoplasia among families of Jewish Indian ancestry.  Hypopigmentation is not a feature of isolated foveal hypoplasia secondary to such mutations but misrouting of optic nerve axons may be present.  Nystagmus and reduced vision but no anterior segment abnormalities were present.

With the widespread utilization of OCT measurements, we have learned that underdevelopment of the fovea can be a feature of numerous ocular disorders (more than 20 in this database).  In most conditions, the foveal dysplasia is part of a disease complex as in foveal hypoplasia with anterior segment dysgenesis (609218).

Non-syndromic cone-rod dystrophies can be either autosomal dominant, autosomal recessive or X-linked and are caused by defects in at least 17 different genes.  This database entry discusses only the autosomal disorders.  See X-linked cone-rod dystrophies in a separate entry.

Cone-rod dystrophies inherited in an autosomal dominant pattern include:

CORD2 (120970) is caused by mutations in CRX at 19q13.3, a homeobox gene responsible for the development of photoreceptor cells.  These are responsible for 5-10% of autosomal dominant cone-rod dystrophy cases (602225) and can also cause one type (LCA7) of Leber congenital amaurosis (602225) and a late-onset retinitis pigmentosa phenotype.

CORD5 (600977) is caused by mutations in the PITPNM3 gene at 17p13.1. 

CORD6 (601777) is caused by a mutation in GUCY2D in a similar location on chromosome 17. 

CORD7 (603649) is caused by mutations in RIMS1 at 6q12-q13.

Mutations in AIPL1 (604392), located in the same region, usually causes a form of Leber congenital amaurosis (LCA4) as well as retinitis pigmentosa (604393) but has also been reported in a cone-rod pigmentary retinopathy.

CORD11 (610381) is caused by mutations in RAXL1 (19p13.3).

CORD12 (612657) results from mutations in the PROM1 gene (4p15.3).

Mutations in the gene GUCA1A on chromosome 6p21.1 causes CORD14 (602093).

An as yet unclassified autosomal dominant type of cone-rod dystrophy has recently been localized to 10q26.

Cone-rod dystrophies inherited in an autosomal recessive pattern include:

Mutations in ABCA4 at 1p21-p13 is responsible for 30-60% of cases of autosomal recessive CRD (CORD3; 604116) .  ABCA4 is also known to cause autosomal recessive Stargardt disease.

CORD8 (605549) has been found in a single consanguineous family and the mutation localized to 1q12-q24.

ADAM9 (602713) at 8p11 and 8p11.23 contains mutations that have been shown to cause autosomal recessive CORD9 in several consanguineous families.

Mutations in RPGRIP1 (14q11) are responsible for CORD13 (608194).

The CDHR1 gene (10q23.1) contains mutations that cause CORD15 (613660).

Other autosomal CRD disorders are CORD1 (600624) described in a single individual and possibly those due to mutations in HRG4 at 17q11.2 (604011).

Syndromal cone-rod dystrophies:

Cone-rod dystrophy may also be associated with other syndromes, such as Bardet-Biedl syndrome (209900), or spinocerebellar ataxia Type 7 (164500), autosomal recessive amelogenesis imperfecta with cone-rod dystrophy or Jalili syndrome (217080), neurofibromatosis type I (162200), and hypotrichosis with juvenile macular dystrophy and alopecia (601553).  Metabolic disorders associated with cone-rod dystrophy include Refsum disease with phytanic acid abnormality (266500) and Alport syndrome (301050). 

Cone-Rod Dystrophy 19 (615860) has been associated with male infertility as the result of mutations in TTLL5 affecting both photoreceptors and sperm.

This is an autosomal dominant disorder usually due to a heterozygous mutation in the PAX6 gene (11p13).  However, some patients with typical features do not have a mutation in this gene suggesting that there is genetic heterogeneity.  Some patients without point mutations nevertheless have defects in adjacent DNA suggesting a positional effect.  The possibility of autosomal recessive inheritance in some families with parental consanguinity cannot be ruled out.  The PAX6 gene plays an important role in iris development as it is also mutant in simple aniridia (106210) and in Peters anomaly (604229).

Mutations in the ITPR1 gene have also been identified in Gillespie syndrome.