Lattice corneal dystrophy is generally divided into three subtypes. The classification has been made mainly by clinical and pathological findings. LCD I is characterized by prominent delicate linear opacities that tend to be mainly in the superficial corneal stroma accompanied with epithelial erosions.
During the past decade, several autosomal dominant hereditary corneal dystrophies had been related to mutations in TGFBI/BIGH3
. Nearly 30 different mutations in TGFBI
have been identified in families with variants of LCD [11
]. Therefore, due to such genetic heterogeneity, it is necessary to identify which specific mutations are carried by the patient to assess a final diagnosis. However, in clinical practice, we may occasionally encounter patients with atypical clinical features of corneal dystrophy, which is difficult to diagnose by clinical features only.
In this present study, we report three Chinese pedigrees with variable clinical features where misdiagnosis had been made in some of the patients. Since phenotypic variations within these families are apparent, some patients’ clinical features of lattice corneal dystrophy are quite atypical. For this reason, classifications of the phenotype for these patients are very difficult. Genetic analysis of TGFBI showed that all affected members of the family have a heterozygous mutation of R124C, which suggests they belong to a classification of LCD I. They are classified into LCD I by the genetic findings, as this mutation occurs independently in several ethnic groups.
Meesmann’s CD is a rare autosomal dominant corneal dystrophy that preferentially affects young family members. Therefore, the penetrance of Meesmann’s CD should also be nearly 50%. However, from these Chinese families, the penetrance of atypical LCD I patients resembling Meesmann’s CD is only 5.6%, which does not support the diagnosis of Meesmann’s CD. Furthermore, the probability of two mutations occurring in both TGFBI and KRT3 (or KRT12) in two unrelated Chinese families should be extremely rare. To our knowledge, there is no such report in other countries. Although we had not done DNA analysis for KRT3 and KRT12 in the atypical LCD I patients resembling Meesmann’s CD, we prefer the diagnosis of atypical LCD I rather than Meesmann’s CD.
This is the first report of phenotypic variability with the R124C mutation in Chinese LCD I pedigrees. Other reports about atypical LCD I with R124C mutation have been found in a Greek family, a Japanese family, and a Bangladeshi family, which indicates that atypical clinical features could also happen independently in different ethnic origins [21
]. Therefore, to speak of the clinical features of LCD I, we should keep in mind that it may include two subtypes, typical and atypical LCD I, even within the same family. The mechanism of the phenotypic variability with the same mutation and even within the same family still remains unknown and needs further study.
Currently, genetic diagnosis plays an important role in establishing the classification of corneal dystrophy. Molecular genetic analysis could establish reliable clinical diagnostic criteria and could improve the accuracy of clinical diagnosis. The technique of DNA diagnosis could also make prenatal and postnatal DNA diagnosis possible in our clinical practice. Once the Arg124Cys mutation is detected in an individual from these families at birth, it can be expected that he or she will develop corneal lattice dystrophy, which may require keratoplasty in the future.