rod dystrophy

Refsum Disease, Adult

Clinical Characteristics
Ocular Features: 

A retinitis pigmentosa-like retinopathy is the major ocular manifestation of this disease.  There is typical night blindness and visual field constriction.   Rod ERG responses are usually subnormal.  However, central acuity is also reduced due to a degenerative maculopathy.   Cataracts and optic atrophy are common.  The macula may undergo progressive degeneration and optic atrophy is not uncommon.  Some patients have defective pupillary responses.

Systemic Features: 

Onset of symptoms is usually late in the first decade and sometimes into the third decade.  There is usually a polyneuropathy with impaired motor reflexes and paresis in the limbs.  A progressive sensorineural hearing loss occurs in many patients.  Sensory deficits also occur.  Some have ataxia and skin changes of ichthyosis.  Anosmia is a near universal feature.  Heart failure may occur and cardiac abnormalities such as conduction defects can occur.  A variety of skeletal abnormalities such as pes cavus, short fourth metatarsals, and evidence of epiphyseal dysplasia have been reported.  There is considerable clinical heterogeneity even within families.

Phytanic acid oxidase activity as measured in fibroblasts is often low while serum phytanic acid is increased.  The cerebrospinal fluid contains increased protein but no increase in cells.

Genetics

This disorder results from mutations in the PHYH (PAHX) gene (10pter-p11.2) encoding phytanoyl-CoA hydroxylase, or, more rarely in PEX7 (6q22-q24) encoding peroxin-7 resulting in an uncommon condition (10% of cases) sometimes called adult Refsum disease-2. 

Mutations in the latter gene also cause rhizomelic chondrodysplasia punctata type 1 (215100) which does not have all of the neurological features or the retinopathy.

There is also so-called infantile form of Refsum disease (266510).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

A diet low in phytanic acid can lead to improvement in the neurologic symptoms such as the ataxia and polyneuropathy but must be instituted in early stages of the disease.  This approach may not be as beneficial for the visual or auditory symptoms.

References
Article Title: 

Night Blindness, Congenital Stationary, CSNB1A

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  The photopic ERG is usually abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision.  Nystagmus and photophobia are usually not features.  Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies.  The amount of pigmentary retinopathy is highly variable. 

CSNB1A, or type 1A, is associated with myopia which ranges from mild to severe.  Rod function is completely absent.  Nystagmus and strabismus are inconsistent findings.   Visual acuity ranges from 20/30 to 20/200.  Retinal pigmentation is usually normal in the X-linked forms.  Night blindness is more severe in this form than in another X-linked CSNB, type 2A (300071). 

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

Congenital stationary night blindness type 1A is an X-linked disorder caused by a mutation in the NYX gene located at Xp11.4.  Only males are affected and carrier females do not have clinical disease (although homozygous females with typical findings have been described).

Approximately 45% of X-linked CSNB are of this type while about 55% have another X-linked form known as CSNB2A, or type 2A (300071) resulting from a mutation at Xp11.23.  A single patient with high myopia absent night blindness with a mutation in the NYX gene has been reported.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.

References
Article Title: 
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