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.       


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).  


Treatment Options: 

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

Article Title: 


Sundin OH. Genetics of Fuchs Corneal Dystrophy Comes of Age: Sweet Repeats. JAMA Ophthalmol. 2015 Sep 24:1.  [Epub ahead of print].

PubMedID: 26402556

Du J, Aleff RA, Soragni E, Kalari K, Nie J, Tang X, Davila J, Kocher JP, Patel SV, Gottesfeld JM, Baratz KH, Wieben ED. RNA toxicity and missplicing in the common eye disease fuchs endothelial corneal dystrophy. J Biol Chem. 2015 Mar 6;290(10):5979-90.

PubMedID: 25593321

Mootha VV, Hussain I, Cunnusamy K, Graham E, Gong X, Neelam S, Xing C, Kittler R, Petroll WM. TCF4 Triplet Repeat Expansion and Nuclear RNA Foci in Fuchs' Endothelial Corneal Dystrophy. Invest Ophthalmol Vis Sci. 2015 Feb 26;56(3):2003-11.

PubMedID: 25722209

Riazuddin SA, Parker DS, McGlumphy EJ, Oh EC, Iliff BW, Schmedt T, Jurkunas U, Schleif R, Katsanis N, Gottsch JD. Mutations in LOXHD1, a Recessive-Deafness Locus, Cause Dominant Late-Onset Fuchs Corneal Dystrophy. Am J Hum Genet. 2012 Mar 9;90(3):533-539.

PubMedID: 22341973

Stehouwer M, Bijlsma WR, Van der Lelij A. Hearing disability in patients with Fuchs' endothelial corneal dystrophy: unrecognized co-pathology? Clin Ophthalmol. 2011;5:1297-301.

PubMedID: 21966205

Sundin OH, Broman KW, Chang HH, Vito EC, Stark WJ, Gottsch JD. A common locus for late-onset Fuchs corneal dystrophy maps to 18q21.2-q21.32. Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3919-26.

PubMedID: 16936105