Cataract 32, Multiple Types

Clinical Features

Moross et al. (1984) reported 4 persons in 3 generations of a family with an apparently balanced translocation t(2;14)(p25;q24) and anterior polar cataracts. Anterior polar cataracts are small opacities on the anterior surface of the lens, which do not usually interfere with vision.

Pras et al. (2006) examined 28 family members from 3 Moroccan Jewish families with autosomal dominant posterior polar cataract (CTPP). The phenotype showed slow progression with age, the opacity being initially evident at 3 to 4 years of age as a barely detectable mat reflex of the posterior capsule. This haziness progressed over the following years into a well-demarcated 2- to 3-mm disc confined to the posterior lens pole, eventually becoming a dense opaque plaque. There was variable pathology in adjacent lens compartments, including scattered cortical white punctate opacities in the early stages and later posterior cortical extensions progressing to form a presenile nuclear sclerotic cataract by 40 to 50 years of age. Family members had no other ocular or systemic abnormalities, and there was generally full recovery of normal visual acuity following cataract extraction.

Pathogenesis

Moross et al. (1984) stated that 3 mechanisms had been postulated for the formation of anterior polar cataracts: imperfect separation of the lens from the surface ectoderm during the fifth week of embryologic development; secondary changes in the epithelial cells with formation of an abnormal mass in the region of the anterior pole; and incomplete resorption of blood vessels and mesoderm at the anterior pole of the embryonic lens.

Mapping

In a genomewide scan of 22 members of 2 Moroccan Jewish families with autosomal dominant posterior polar cataract, Pras et al. (2006) found linkage to chromosome 14q. Fine mapping using additional samples from another Moroccan Jewish family with CTPP yielded a maximum lod score of 5.19 with the marker D14S274 (theta = 0), and haplotype analysis identified an 11.3-cM (11.23-Mb) critical region between D14S980 and D14S1069 on chromosome 14q22-q23. Visual inspection of the haplotypes cosegregating with CTPP in the families suggested a common founder for the 3 families. One affected individual was homozygous for disease chromosomes from both parents, but there was no detectable clinical difference compared to patients who inherited a single disease chromosome.

Inheritance

The transmission pattern of cataract in the families reported by Moross et al. (1984) and Pras et al. (2006) was consistent with autosomal dominant inheritance.

Cytogenetics

Moross et al. (1984) reported 4 persons in 3 generations of a family with an apparently balanced translocation t(2;14)(p25;q24) and anterior polar cataract. The transmission pattern was consistent with autosomal dominant inheritance.

Miller et al. (1992) described a female infant with multiple congenital anomalies associated with a rare terminal deletion of chromosome 14; the karyotype was that of mos46,XX/46,XX,del(14)(q32.3). There was unilateral nuclear cataract of the left eye. Miller et al. (1992) suggested that the finding, together with the report of Moross et al. (1984), indicates the localization of a cataract-producing mutation on chromosome 14. It should be noted, however, that the abnormality in the case of Miller et al. (1992) was situated more distal.

Frances et al. (1997) described a brother and sister, born of healthy, second-cousin parents, with arrhythmogenic right ventricular dysplasia (ARVD) and cataracts. The brother had anterior polar cataracts and the sister had a 'linear-shaped opacification of the crystalline lens in the anterior and posterior subcapsular zones.' Because one form of ARVD (107970) had been mapped to 14q23-q24, the tentative location of a cataract locus, the authors suggested the possibility of pleiotropy or a contiguous gene syndrome.

Molecular Genetics

Exclusion Studies

In affected members of 3 Moroccan Jewish families with autosomal dominant posterior polar cataract mapping to chromosome 14q22-q23, Pras et al. (2006) excluded mutations in the SIX1 (601295), SIX4 (606342), SIX6 (606326), OTX2 (600037), and ARHJ (607653) genes.