optic disc pallor

Retinitis Pigmentosa 47

Clinical Characteristics
Ocular Features: 

Onset of night blindness and field constriction symptoms occur during the 4th and 5th decades of life.  Pigmentary abnormalities of the retina are the hallmark of this condition.  Retinal thinning, bone spicule pigmentation, vascular attenuation, optic disc pallor, and pigmentary atrophy have all been noted.

In patients with the autosomal dominant form of this disease, rod function is severely impaired or absent as evidenced by ERG studies.  Cone responses are often reduced on an age-related basis and in the range of 85-95% below normal.  As expected, dark-adapted visual thresholds are elevated and visual fields are restricted peripherally.  Loss of vision is age-related but some individuals can retain acuities of 20/35 to 20/40 into their sixth decade.  It is more common for acuities to be in the range of 20/200 to 20/400 later in life.

Systemic Features: 

No systemic disease is associated with this disorder.

Genetics

Mutations in the SAG gene (2q37) are responsible for this form of RP.  Both autosomal recessive and autosomal dominant modes of inheritance have been reported.

In one family with homozygous mutations a sib had features of Oguchi disease which also results from homozygous mutations in SAG.

Among Hispanic families in the southwestern US, heterozygous mutations in SAG are a common cause of autosomal dominant retinitis pigmentosa.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported for this disorder.

References
Article Title: 

A Novel Dominant Mutation in SAG, the Arrestin-1 Gene, Is a Common Cause of Retinitis Pigmentosa in Hispanic Families in the Southwestern United States

Sullivan LS, Bowne SJ, Koboldt DC, Cadena EL, Heckenlively JR, Branham KE, Wheaton DH, Jones KD, Ruiz RS, Pennesi ME, Yang P, Davis-Boozer D, Northrup H, Gurevich VV, Chen R, Xu M, Li Y, Birch DG, Daiger SP. A Novel Dominant Mutation in SAG, the Arrestin-1 Gene, Is a Common Cause of Retinitis Pigmentosa in Hispanic Families in the Southwestern United States. Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2774-2784.

PubMed ID: 
28549094

Retinitis Pigmentosa 78

Clinical Characteristics
Ocular Features: 

Onset of visual complaints is in the third or fourth decades with night blindness and visual field defects.  These symptoms are progressive with the oldest of three reported patients having 20/1250 vision at 51 years of age.  Classic signs of retinitis pigmentosa are usually present including disc pallor, pigment clumping, peripheral field constriction, and attenuated retinal vessels.  Intraretinal cysts may be detected with optical coherence tomography.  The full-field ERG shows general photoreceptor dysfunction with the rods most severely involved while pattern ERGs shows variable macular involvement.

Systemic Features: 

No systemic disease has been detected in the three reported individuals.

Genetics

Three unrelated individuals have been reported with homozygous or compound heterozygous mutations in the ARHGEF18 gene (19p13.2).   Five different mutant alleles were found among these patients.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported but low vision aids might be helpful.

References
Article Title: 

Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration

Arno G, Carss KJ, Hull S, Zihni C, Robson AG, Fiorentino A; UK Inherited Retinal Disease Consortium., Hardcastle AJ, Holder GE, Cheetham ME, Plagnol V; NIHR Bioresource - Rare Diseases Consortium., Moore AT, Raymond FL, Matter K, Balda MS, Webster AR. Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration. Am J Hum Genet. 2017 Feb 2;100(2):334-342.

PubMed ID: 
28132693

Retinitis Pigmentosa 79

Clinical Characteristics
Ocular Features: 

As in many autosomal dominant conditions, there is considerable clinical heterogeneity and even nonpenetrance among individuals.  Onset may consist of night blindness in early childhood but many patients are not symptomatic until the 6th or 7th decade of life.  The fundus signs are characteristic for retinitis pigmentosa with bone spicule pigmentation clumps, attenuated vessels, optic disc pallor, and peripheral retinal atrophy.  Visual fields are peripherally constricted to variable degrees.   Patches of chorioretinal "degeneration" and choroidal "sclerosis" have been described.  Photophobia, decreased central acuity, and some degree of dyschromatopsia have been reported.  Progression of symptoms is highly variable but central acuity is usually affected at some point.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This autosomal dominant type of retinitis pigmentosa seems to result from heterozygous mutations in the HK1 gene (10q22.1).  Its phenotype is nonpenetrant in some individuals.   

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment has been reported but low vision aids might be helpful especially for near vision.

References
Article Title: 

A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa

Sullivan LS, Koboldt DC, Bowne SJ, Lang S, Blanton SH, Cadena E, Avery CE, Lewis RA, Webb-Jones K, Wheaton DH, Birch DG, Coussa R, Ren H, Lopez I, Chakarova C, Koenekoop RK, Garcia CA, Fulton RS, Wilson RK, Weinstock GM, Daiger SP. A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(11):7147-58.

PubMed ID: 
25190649

Macular Dystrophy with Central Cone Involvement

Clinical Characteristics
Ocular Features: 

This is primarily a cone dystrophy but there is evidence of some rod damage in older patients.  A mild decrease in central acuity is noted by individuals in the third to sixth decades.  Slight pigmentary changes and color vision abnormalities can be documented with the onset of these symptoms and a bull's eye maculopathy and severe atrophy of the central fovea may be present. An enlarging central scotoma with normal periphery can sometimes be identified.  Other patients have an atrophic appearance to the peripapillary area with a pale optic disc.  ERG responses to full-field testing are normal but multifocal studies reveal severely reduced central responses.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

Compound heterozygosity for a missense mutation and a nonsense mutation in the MFSD8 gene (4q28.2) has been found among members of a Dutch sibship suggesting autosomal recessive inheritance.       

The same mutant gene has been identified in some patients with late infantile or early juvenile onset lysosomal storage disease known as neuronal ceroid lipofuscinoses (610951) in which there may be optic atrophy, attenuated retinal vessels, a pigmentary retinopathy, and severe vision loss.   However, it is of note that no members of the Dutch family with the macular cone dystrophy described here had extraocular manifestations.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 
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