KRT12

Corneal Dystrophy, Stocker-Holt

Clinical Characteristics
Ocular Features: 

Stocker-Holt dystrophy is clinically somewhat similar to Meesmann corneal dystrophy but is caused by a different mutation and is therefore discussed separately here.  Stocker and Holt in 1954 described this disorder among 20 descendents from Moravia who settled in North Carolina (Meesmann and Wilke's report in 1939 was based on patients in Germany).  Fine, grayish punctate epithelial opacities were found in the epithelium anterior to Bowman's throughout the entire cornea even in patients as young as 7 months old.  These stain with fluorescein and are accompanied by fine linear opacities that appear in a whorled pattern.  Outside of light sensitivity and glare reported by some patients, few are symptomatic.  Spontaneous, recurrent epithelial erosions can occur.  Corneal sensitivity is reduced. Contact lenses are poorly tolerated.  Visual acuity is generally around 20/50 but can be significantly worse.  Few require keratoplasty.

Meesmann dystrophy (122100) is superficially similar but the opacities are more numerous in the interpalpebral area and the surrounding epithelium is generally clear.

Systemic Features: 

No systemic problems are associated with this corneal disease.

Genetics

Stocker-Holt dystrophy is caused by mutations in KRT12 (17q12).  Like Meesmann dystrophy (122100), it follows an autosomal dominant pattern.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment is largely directed at symptoms from epithelial erosions using hypertonic solutions and sometimes epithelial debridement.  The cystic changes tend to recur following removal of the offending epithelium and even after corneal replacement.

References
Article Title: 

Corneal Dystrophy, Meesmann

Clinical Characteristics
Ocular Features: 

Meesmann corneal dystrophy is a disorder of the epithelium and its basement membrane.  Onset is early, even in the first year of life and begins with irritation and often photophobia.  However, some patients remain asymptomatic for many years.  Vision is usually impacted only to a mild degree as a result of surface irregularities and epithelial cysts, which are concentrated most commonly in the interpalpebral regions.  They may only be visible with slit lamp examination. The cysts are usually in the basal cells and are filled with PAS positive material. They may coalesce to form refractile lines and later in life become more opaque. The basement membrane appears coarse and is often abnormally thick.  Bowman layer and the stroma are unaffected.  Corneal sensitivity is reduced.

Stocker-Holt dystrophy (122100) is often lumped with Meesmann dystrophy and, while it is a clinically similar disease, it is usually caused by a different mutation.  The 20 patients reported by Stocker and Holt in 1954 were descendents from Moravia who settled in North Carolina (Meesmann and Wilke's report in 1939 was based on patients in Holstein, Germany).

Systemic Features: 

No systemic disease is associated with this dystrophy.

Genetics

This is a genetically heterogeneous autosomal dominant disorder resulting from mutations in several genes encoding cornea-specific keratins, K12 by KRT12 (similar to Stocker-Holt dystrophy; 122100) and K3 by KRT3 (Meesmann dystrophy) located on chromosomes 17 (q12) and 12 (q13), respectively.

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Contact lenses are poorly tolerated and keratoplasty is rarely indicated.  Treatment is largely directed at symptoms with hypertonic solutions and sometimes with epithelial debridement.  The cystic changes tend to recur following removal of the offending epithelium and even after corneal replacement.

The Arg135Thr mutation in the KRT12 gene found in the German family reported by Meesman and Wilke in 1939 (and a common founder mutation in Europe) can be selectively silenced in vitro by an allele-specific short interfering RNA (siRNA) suggesting a novel approach to therapy.

References
Article Title: 
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