Diagnostic value of ophthalmologic findings in myotonic dystrophy: Comparison with risks calculated by haplotype analysis of closely linked restriction fragment length polymorphisms

Abstract

To determine diagnostic value of lens opacities in myotonic dystrophy (DM), we examined 98 at-risk members of 9 DM kindreds. Haplotype analysis of restriction fragment length polymorphisms (RFLPs) using ApoC2, CKMM, and pEFD4.2 supported the diagnosis of DM in 33 and excluded the diagnosis in 51 members. The sensitivities of bilateral iridescent lens opacities, posterior cortical lens opacities, orbicularis oculi weakness, low intraocular pressure, ptosis, and ocular myotonia were 46.7, 50.0, 60.6, 59.3, 51.5, and 3.0%, while their specificities were 100.0, 100.0, 98.0, 94.1, 96.1, and 100.0%, respectively. A peripheral pigmentary degeneration and central macular lesions of retina were not found on indirect fundoscopy. In 86.2% of DM patients, bilateral iridescent lens opacities, posterior cortical lens opacities, or both were present. Unilateral iridescent lens opacities occurred in only 3 of our DM patients, and 2 of non-DM relatives showed a few unilateral iridescent particles. Posterior cortical lens opacities in DM patients always affected both eyes in this series. We conclude that 1) bilateral iridescent lens opacities and posterior cortical lens opacities are highly specific for DM and useful for establishing clinical diagnosis of DM, 2) unilateral iridescent lens opacities are infrequent in DM and are seen in some non-DM members, and 3) ocular myotonia and clinical retinopathies are rare in DM.

Eight years' experience of direct molecular testing for myotonic dystrophy in Wales

“…However, subsequent molecular analysis showed that most such subjects in this and other kindreds did not carry the myotonic dystrophy mutation 816 By contrast, Ashizawa et al ,17 analysing lens opacities alone in a series of 98 subjects at risk, found 100% specificity for opacities considered characteristic, when compared with a prediction from closely linked DNA markers. Outside the family context, lens opacities are less specific, Giordano et al 18 finding apparently characteristic lens opacities in 10 of 1400 healthy subjects, none of whom showed the myotonic dystrophy mutation.…”

Myotonic dystrophy protein kinase (DMPK) induces actin cytoskeletal reorganization and apoptotic-like blebbing in lens cells

“…The formation of cataracts in the eye lens and the myotonia of skeletal muscle are the most penetrant phenotypes in DM patients [Ashizawa et al, 1992b]. Furthermore, DMPK mRNA and protein are expressed in the epithelial and cortical fiber cells of human and bovine lenses [Dunne et al, 1996a].…”

Reassessment of the Specificity of Lens Opacities in Myotonic Dystrophy

“…In fact, bilateral cortical irides cent and posterior cortical lens opacities were found in 1 in every 140 individuals in the Ital ian population with a sevenfold higher fre quency than that reported by Ashizawa et al [7], Actually the 3 patients who underwent cataract surgery in group I could represent a distortion factor in the calculation of the fre quency of cataract in the tested population sample. However, approximately the same None of the individuals with the described lens opacities showed preclinical neurological signs of DM.…”

“…Two further analogous cases were re ported by MacMillan et al [10] and Reardon et al [ 11 ]. Contrarily to that seen by Ashizawa et al [7], these studies suggest that not all cases of early cataract typical of DM are corre lated to the presence of the mutation in the DM gene, even in affected families, and that a reassessment of the specificity of the ophthal mic sign in DM is required.…”

“…Ashizawa et al [7] studied the specifici ty and sensitivity of these ocular anomalies in a group of relatives of DM patients including individuals with no muscle involvement and no definitive diagnosis, in which inheritance of the DM gene was assessed by genetic analy sis following the segregation of closely linked markers. These authors showed that bilateral cortical iridescent and posterior cortical lens opacities are highly specific and, when they are combined, highly sensitive for DM.…”