Corneal endothelial dystrophy is characterized by thickening and opacification of the cornea, altered morphology of the endothelium, and secretion of an abnormal collagenous layer at the Descemet membrane. There are both autosomal dominant (CHED1; 121700) and autosomal recessive ... Corneal endothelial dystrophy is characterized by thickening and opacification of the cornea, altered morphology of the endothelium, and secretion of an abnormal collagenous layer at the Descemet membrane. There are both autosomal dominant (CHED1; 121700) and autosomal recessive (CHED2) forms, with the latter being more common and more severe (summary by Vithana et al., 2006).
Maumenee (1960) reported several cases in which family histories of corneal endothelial dystrophy suggested recessive inheritance. In each of 2 families a brother and sister were affected. In view of the degree of corneal clouding, vision is often ... Maumenee (1960) reported several cases in which family histories of corneal endothelial dystrophy suggested recessive inheritance. In each of 2 families a brother and sister were affected. In view of the degree of corneal clouding, vision is often remarkably good. Redmond (1946) described 3 affected daughters of normal but consanguineous parents. Judisch and Maumenee (1978) reviewed autosomal dominant and autosomal cases of CHED. They found that in the recessive form corneal clouding is observed at birth or within the neonatal period, nystagmus is often present, but no photophobia or epiphora is seen. In the dominant form, corneal opacification is usually seen in the first or second year of life and progresses slowly, photophobia and epiphora may be the first signs of the dystrophy, and nystagmus is infrequently seen. Kirkness et al. (1987) reviewed 23 patients with what they called congenital hereditary corneal edema of Maumenee, including 6 from a family with autosomal dominant inheritance previously reported by Pearce et al. (1969) and 17 from other families with either definite (8) or probable (9) autosomal recessive inheritance. They commented that in spite of significant corneal clouding from birth or early childhood, visual development is often little impaired. Penetrating keratoplasty carries a relatively good surgical prognosis and can produce a substantial visual gain even when carried out late in life. Their experience suggested that the recessive form has an earlier age of onset and earlier age of presentation to medical attention. McCartney and Kirkness (1988) stated that secondary epithelial changes are seen in CHED1 and CHED2, but that spheroidal degeneration of stroma is seen more commonly in CHED1. Changes at the level of Descemet membrane showing failure to regulate growth is seen in CHED2, whereas CHED1 is associated with development of a fibrillary posterior collagen layer.
Vithana et al. (2006) considered the SLC4A11 gene (610206), which resides within the CHED2 locus refined by them, a candidate for causative mutations. The SLC4A11 gene encodes a sodium-borate cotransporter essential for cell growth and proliferation in mammalian ... Vithana et al. (2006) considered the SLC4A11 gene (610206), which resides within the CHED2 locus refined by them, a candidate for causative mutations. The SLC4A11 gene encodes a sodium-borate cotransporter essential for cell growth and proliferation in mammalian cells. Comparative SAGE analysis of gene expression profiles in normal corneas and those from patients with Fuchs corneal endothelial dystrophy (see 136800) showed that SLC4A11 is downregulated in corneas of Fuchs patients. Vithana et al. (2006) confirmed expression of SLC4A11 in corneal endothelium by RT-PCR. Furthermore, in situ hybridizations in embryonic mouse eyes showed expression in the cornea at embryonic day 18, equivalent to human gestational month 5, the time at which CHED pathology develops in humans. Vithana et al. (2006) described 7 different mutations in the SLC4A11 gene in 10 families with CHED2. Mutations cause loss of function of the protein either by blocking its membrane targeting or by nonsense-mediated decay. The report of Vithana et al. (2006) concerning CHED2 was the first of a human disease linked to a transporter that reportedly regulates the intracellular concentration of boron, the homeostasis of which is poorly understood in humans. Identification of loss-of-function mutations in the first gene underlying CHED could facilitate gene replacement therapy in this most accessible part of the eye.