corneal guttae

Corneal Dystrophy, Fuchs Endothelial, Late Onset 2

Clinical Characteristics
Ocular Features: 

The signs and symptoms of this disorder are similar to those of other adult endothelial dystrophies.  Guttae appear in the fourth or fifth decade of life and gradually increase in number.  Diffuse corneal edema eventually develops with a corresponding decrease in acuity.  In late stages the corneal edema involves all layers including the epithelium, leading to painful corneal erosions. 

Systemic Features: 

Some patients with FECD3 report hearing impairment but this has not been studied and may be simply an age-related association.  It is of interest that among an unclassified series of patients with FCD the frequency of hearing loss was higher than in matched controls.       

Genetics

A mutation in LOXHD1 (18q21.2-q21.32) was originally thought to be responsible for this form of Fuchs in a multigenerational pedigree but is now considered an insignificant variant.  More recent evidence suggests that heterozygous trinucleotide repeat expansions in the TCF4 transcription factor gene at 18q22 are responsible.

There is considerable genetic heterogeneity in adult endothelial dystrophy which makes the nosology confusing especially since the clinical features are similar.  A similar late onset autosomal dominant disease [Fuchs Endothelial Dystrophy, Late Onset (610158)], sometimes labeled FCD2, may result from mutations on chromosome 13, or from changes in ZEB1 on chromosome 10.  Many cases are sporadic, however, and additional genotyping will be necessary in individuals to further clarify the classification of late-onset Fuchs endothelial dystrophy.

There is also an early onset form of Fuchs endothelial dystrophy, (136800).  

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Corneal transplantation for symptomatic patients would likely be helpful but results have not been reported specifically for this type of dystrophy.

References
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Vitreoretinal Degeneration, Snowflake Type

Clinical Characteristics
Ocular Features: 

The retina and vitreous are primarily affected in this disorder.  The age of onset is unknown but characteristic signs can be seen early in the second decade of life.   Early changes include thickening of the cortical vitreous and white dots in the superficial layers of the retina.  The latter are minute yellow-white crystalline deposits more common in the peripheral retina.  Many (83%) patients have early onset cataracts.  Corneal guttae are common (80% of patients).  The vitreous undergoes fibrillar degeneration with liquefaction and eventually appears optically empty.  Many patients experience symptoms of floaters.  The vitreous changes most closely resemble that seen in Wagner syndrome (143200) but with important differences.  In the latter disorder the vitreous changes are membranous, the retinal changes are deeper in location, RPE changes are evident, the choroid and RPE are involved, and the risk of retinal detachment is much higher.  Only 21% of patients with snowflake vitreoretinal degeneration have retinal detachments compared with about 50% in Wagner syndrome.  Retinal vasculature change such as perivascular sheathing and attenuation of arterioles may be seen in both disorders but occur far less commonly in snowflake degeneration.

Based on lack of visual symptoms, the photoreceptors are minimally involved.  Electrophysiologic studies reveal an elevated dark adaptation and reduced scotopic B waves.  Most patients retain excellent vision.  However, the optic nerve may have a waxy pallor and frequently appears flat and lacks a visible cup. 

Systemic Features: 

None.

Genetics

Snowflake vitreoretinal degeneration is an autosomal dominant disorder.   Heterozygous missense mutations have been found in KCNJ13 (2q37) in a single family.  Mutations in the same gene have been identified in rare cases of Leber congenital amaurosis.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Visually significant cataracts may be removed.  Patients need to be observed throughout life to enable prompt intervention when retinal detachments occur.

References
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