Cognition in nephropathic cystinosis: pattern of expression in heterozygous carriers

Abstract

Individuals with cystinosis exhibit specific cognitive deficits in visual spatial function. The purpose of the current study was to examine if obligate heterozygotes of the CTNS mutation have the same pattern of cognitive functioning seen in homozygotes, namely aberrant visual-spatial functioning against a background of relatively intact visual-perceptual functioning and overall cognitive ability. Study participants were 254 adults (100 heterozygotes and 154 controls), ages 17 years 10 months through 74 years 9 months. Tests of intelligence, visual perceptual, and visual spatial functioning were administered. Our results showed that cystinosis heterozygotes demonstrated intelligence within the normal range, and performed similarly to controls on tests of visual-perceptual ability. In contrast, the heterozygotes performed significantly more poorly on each of the visual-spatial tests when compared to controls. Obligate heterozygotes for the CTNS mutation display a similar pattern of visual processing decrements as do individuals with cystinosis. Namely, carriers demonstrate relative weaknesses in visual-spatial processing, while maintaining normal visual perceptual ability and intelligence in the normal range. The visual spatial decrements in heterozygotes were not as marked as those found in individuals with cystinosis, suggesting a gene dosing effect. This study provides an impetus for other studies of gene-behavior relationships in recessive disorders, and may stimulate further interest in the role of aberrant genes on "individual differences" in behavior.

Figure 1

Comparison of Heterozygote and Control group performance on Stanford-Binet subtests. Higher scores indicate better performance. The average standard score for each test is 50. Cystinosis carriers performed significantly more poorly than controls on all subtests (ps < 0.05) except Pattern Analysis.

Figure 2

Comparison of Heterozygote and Control group performance on the Locomotor Maze test. Longer time indicates poorer performance. Carriers performed significantly more poorly than controls (p = .009).

Figure 3

Comparison of Heterozygote and Control group performance on Woodcock-Johnson Spatial Relations. Carriers performed significantly more poorly than controls (p = .0035), although within normal range.

Figure 4

Comparison of Heterozygote and Control group performance on Space Thinking - Flags. Cystinosis carriers performed significantly more poorly than controls (p = .027).