Linkage Analysis of Corneal Fleck Dystrophy (CFD) in a Family with Marked Symptomatology Maps to Chromosome 2q35

Abstract

Abstract: : Purpose:To describe a family affected with Corneal Fleck Dystrophy (CFD) in which the proband was found to have severe symptoms of photophobia and ocular surface irritation. Methods:We identified a family of six in which four members were found to have the clinical features of CFD. Slit–lamp exam was done of all six family members and genetic analysis and confocal microscopy was done on the proband, her two daughters and her father. Results:Pedigree analysis was done on this family. The proband was found to have multiple discrete wreath–like refractile bodies in the corneal stroma that were easily seen on retro–illumination. She also had severe symptoms of photophobia and ocular surface irritation, initially presenting with blepharospasm. Over the course of three weeks this progressed to facial spasm and she required multiple courses of botulinum toxin injection with marked improvement in her symptoms. Her two young daughters were found to have multiple lesions bilaterally, but were symptom free. Her father was found to have refractile bodies in the stroma and was also asymptomatic. The patients’ paternal grandmother and sister were found to be unaffected. Confocal microscopy revealed engorged keratocytes with refractile inclusion bodies within the cytoplasm in the stroma of the affected members. Genetic linkage analysis was done in conjunction with DNA extracted from the blood of four other families and the site of the defect was found to localize to a 24 cM interval flanked by D2S2289 and D2S126 on chromosome 2q35. Conclusions:CFD appears to be an autosomal dominant corneal dystrophy that localizes to chromosome 2q35. It is easily identified by the wreath–like opacities seen on retro–illumination. Contrary to its’ typical presentation, our patient suffered from ocular symptoms that were severe enough to result in blepharo– and facial spasm that was effectively treated with multiple botulinum toxin injections. Confocal microscopy revealed engorged keratocytes with multiple refractile inclusion bodies. Linkage analysis confirms that this dystrophy is distinct from the other autosomal dominantly inherited corneal dystrophies in its localizing to chromosome 2q35, a region of the genome only rarely associated with mucopolysaccharidosis (MPS). Also, this represents the only autosomal dominant MPS described.

Keywords: cornea: basic science • gene mapping • cornea: clinical science