vitreous degeneration

Pigmented Paravenous Chorioretinal Atrophy

Clinical Characteristics
Ocular Features: 

This is a rare type of pigmentary retinopathy with few symptoms in many patients.  Pigment clumps in the form of bone spicules in a paravenous distribution appear as young as 1 year of age and may be present congenitally.  The pigment may begin peripherally and is often segmental but eventually progresses centrally along with chorioretinal atrophy involving the majority of the fundus.  For unknown reasons, males are more severely affected than females.  In one family the retinal changes were associated with hyperopia, esotropia and vitreous degeneration (cells and liquefaction).  There is considerable variation in expressivity among patients and the vision and fundus pigmentation can be highly asymmetrical in the two eyes.  ERG abnormalities likewise vary widely with decreased photopic responses in some individuals and complete lack of both scotopic and photopic responses in severely affected eyes.  Decreased night vision is not a symptom.

This is generally considered to be a stationary condition but long term follow up reveals progression of pigmentary changes, chorioretinal atrophy and increasing constriction of the peripheral visual field.  Symptoms of decreased vision may be noted as early as 3 months of age.  Some patients retain vision of 20/20 or 20/30 into midlife whereas others in the first decade already have count fingers vision.  Likewise the size of the visual field varies widely and is not correlated with age.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

This is an autosomal dominant disorder caused by heterozygous mutations in the crumbs homolog 1 (CRB1) gene (1q31.3).

CRB1 mutations have been identified in other retinal disorders including nanophthalmos with retinitis pigmentosa, pigmented paravenous chorioretinal atrophy (172870), retinitis pigmentosa-12 (600105), and Leber congenital amaurosis 8 (613835).  No consistent retinal phenotype has been found, however.  There is often marked asymmetry between the two eyes and the rate of visual loss varies widely.  Most individuals have some patchy areas of hypoautofluorescence in the posterior pole with variable amounts of pigmentary anomalies from mild speckling to frank bone spicule formation.

   

 

   

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No effective treatment is available although low vision aids are likely to be helpful in selected patients.

References
Article Title: 

Myopia 2, Autosomal Dominant, Nonsyndromal

Clinical Characteristics
Ocular Features: 

Nonsyndromal, high myopia (over 6 D) has been found in multiple multigenerational families.  Most individuals have no other ocular problems but a small percentage develop degenerative changes in the retina, particularly in the macula (Fuchs spot).  A few individuals have posterior staphylomas with significant vitreoretinal changes conferring higher risks of retinal detachments and macular holes.  Vitreous traction is often present.  The macula in such cases is may be thickened and microcystic with areas of frank retinoschisis.  Of course, vitreous degeneration and retinal detachments are well known sequelae of high myopia. 

Systemic Features: 

There are no systemic features by definition. 

Genetics

Refractive errors are continuous traits with a wide range in most populations.  This suggests that many developmental and heritable (and perhaps environmental) components are responsible.  No specific mutation has been identified but a number of 'susceptibility' loci have been mapped.

Myopia 2 has been linked to a susceptibility locus at 18q11.31.

Evidence of heritability in both syndromal and isolated myopia comes from several sources.  For example, high myopia is a common feature in familial collagenopathies such as Marfan syndrome (154700), Kniest dysplasia (156550), and Stickler syndrome (108300). Multigenerational families with isolated myopia have been reported as well and mutations in multiple genes (at least 18) have been associated with these.  Heredibility studies using twin pairs have identified additional mutations (609256).  Further, the prevalence of myopia among children increases in the presence of parental myopia.

The transmission pattern in most families to which susceptibility loci have been linked is autosomal dominant.  However, a susceptibility locus has been mapped to 14q22.1-q24.2 in several families with good evidence for autosomal recessive inheritance (255500).  In addition, two loci on the X chromosome have been linked to presumed X-linked myopia (MYP1 [310460] at Xq28 and MYP13 [300613] at Xq23-q25).  A patient with high myopia has been reported with a mutation in the NYX gene on the X-chromosome.  This patient did not have congenital stationary night blindness of the type CSNB1A (310500) in which NYX is usually mutated.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Correction of the refractive error is primary.  High myopes require periodic evaluation throughout life and prompt surgical intervention for retinal detachments.  In extreme myopia it may be especially prudent for individuals to avoid impact sports. 

References
Article Title: 

Marshall Syndrome

Clinical Characteristics
Ocular Features: 

Myopia is a common feature.  The globes appear prominent with evident hypertelorism, perhaps in part due to shallow orbits.  The vitreous is abnormally fluid.  The beaded vitreous pattern seen in Stickler syndrome type II (604841), with which Marshall syndrome is sometimes confused, is not seen in Marshall syndrome, nor is the same frequency of retinal detachments.  Congenital or juvenile cataracts were present in Marshall’s original family.

Systemic Features: 

The midface is flat with some features of the Pierre-Robin phenotype.  The nasal root is flat and the nares anteverted.  Patients tend to be short in stature and joints are often stiff.  Small iliac wings and a thickened calvarium can be seen radiologically together with other bone deformities.  Abnormal frontal sinuses and intracranial calcifications have also been reported.  Sensorineural hearing loss may be noted during the first year of life with age-related progression.  Osteoarthritis of the knees and lumbosacral spine begins in the 4th and 5th decades.  Features of anhidrotic ectodermal dysplasia such as hypohidrosis and hypotrichosis are present in some patients.  Individuals may have linear areas of hyperpigmentation on the trunk and limbs.

Genetics

The syndromal status of Marshall syndrome as a unique entity remains uncertain inasmuch as there are many overlapping clinical features with Stickler syndrome type II (604841) and both result from mutations in the COL11A1 gene (1p21).  Autosomal dominant inheritance is common to both although autosomal recessive inheritance has been proposed for a few families with presumed Marshall syndrome. Stickler syndrome type II (604841) and Marshall syndrome may be allelic or even the same disorder.

Pedigree: 
Autosomal dominant
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for this disorder beyond cataract removal.  Patients need to be monitored for retinal breaks and detachments.

References
Article Title: 
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