Nonverbal cognitive abilities
Nonverbal intellectual abilities1
for all 18 patients were assessed using the Leiter International Performance Scale-Revised – Brief IQ score. Consistent with prior findings, 78% of participants fell within the range of Intellectual Disability. Eleven percent (2 subjects) fell in the borderline range, 6% (1 subject) in the low-average range, and 6% (1 subject) in the average range ().
Nonverbal fluid reasoning (Leiter-R Fluid Reasoning Index; n = 18) ranged from the moderate range of Intellectual Disability to the average range (Mean = 65, SD = 17, range = 48 to 100). Consistent with prior findings, nonverbal fluid reasoning was found to be a strength relative to overall nonverbal IQ by about ½ a standard deviation on average, though this effect was not statistically significant due to high within-group variance ().
Nonverbal memory (Leiter-R Associative Memory Scale; n = 14) was consistent with nonverbal intellectual functioning, with 43% of subjects falling in the mildly delayed range, 36% in the borderline range, and 21% in the low-average range ().
Verbal cognitive abilities
Verbal intellectual abilities (SB5; n = 18) were within the range of Intellectual Disability for 83% of participants, with 44% falling in the moderate range, and 39% in the mild range (Mean = 57, SD = 13, range = 43 to 90). Two subjects (11%) fell in the borderline range, and 1 (6%) in the average range. In contrast to the nonverbal test results, fluid reasoning in the verbal realm was not found to be a strength relative to overall verbal IQ (F = 1.63, p = .2) ().
Receptive vocabulary skills, as measured by the PPVT-IV (n = 18), were better developed than overall verbal cognitive skills. Fifty-five percent fell in the range of Intellectual Disability, with a third (33%) in the borderline range, and 2 subjects (11%) falling in the low average range (Mean = 63, SD = 15, range = 33 to 88).
Visuomotor integration skills (VMI; n = 18) were in the range of Intellectual Disability for a majority of subjects (83%), with the remaining 17% falling in the borderline range. Non-motor visuoperceptual skills (VMI Visual Perception) showed a similar pattern, with 50% falling in the moderate range, 22% falling in the mild range, 11% falling in the borderline range, and 1 subject falling in the low average range.
The Vineland-II Adaptive Behavior Scales (VABS-II) Survey Interview Form was completed for 17 subjects. Overall adaptive functioning was judged to fall in the range of Intellectual Disability for 70% of subjects, with 24% in the borderline range, and one subject (6%) in the low average range. Socialization skills were indicated as a relative strength (Mean = 75, SD = 12), and Daily Living Skills were an area of relative difficulty (Mean = 65, SD = 9), and the difference between these two scales was significant (F = 7.466, p = .01). Communication skills fell between these two ranges (Mean = 68, SD = 9).
The VABS-II Motor Scale was completed for the five children under age 7 years. Motor skills were rated as falling in the mild range of disability for all 5 subjects (Mean = 59, SD = 2).
The VABS-II behavioral profile was completed for 16 subjects. Twenty-five percent had internalizing scores in the Average range, 50% had Elevated internalizing scores, and 25% had Clinically Significant internalizing problems. Thirty-eight percent had externalizing scores in the Average range, whereas 56% had Elevated externalizing scores and one subject (6%) had a Clinically Significant externalizing score.
Difference by mutation
Because the disease causing mutations of two patients differ from the other patients’ change (one male p.G13C, one male p.T58I), we reviewed their test results individually and compared them to the mean for the study group. On the Leiter-R measure, both patients scored more than 1 SD above the mean on the Fluid Reasoning scale. The patient with the p.G13C mutation also scored more than 1 SD above the mean on the Leiter-R Memory Screen and the PPVT-IV, and more than 3 SD above the mean on the SBV (scores ranging from the Low Average to Average range on these scales). The patient with the p.T58I scored more than 2 SD below the mean in the VABS-II Daily Living Skills, and more than 1.5 SD below the mean in VABS-II Socialization.
To examine developmental trends, subjects were divided into three age groups: Child (age 10 years and under; n = 6), Adolescent (age 11 to 17; n = 7), and Adult (age 18 and up; n = 5)(see ). Overall, the Child group showed significantly better nonverbal cognitive functioning, with Leiter-R Brief IQ scores in the borderline range (M = 72) relative to the Adolescents who were in the mild range of disability (M = 55) and the Adults who were in the moderate range of disability (M = 41)(F = 9.84, p < .002). This trend appears largely driven by differences in nonverbal fluid reasoning, with the Child group falling in the low average range (M = 81), the Adolescent group in the mild range of disability (M = 64), and the Adult group falling in the moderate range (M = 49)(F = 9.54, p = .002). Relative performance on the VMI also declined across age groups, with the Child and Adolescent groups falling in the mild range of disability and the Adult group falling in the moderate range (F = 5.256, p = .02). Interestingly, on the PPVT-IV, the opposite trend was observed, with the Adult group showing better relative verbal skills compared to the Child group, though this difference was only marginally significant (F = 3.7, p = .09). There were no age cohort effects in caregiver-reported adaptive functioning, though there was a non-significant trend toward greater maladaptive behaviors in the Child group (F = 3.00, p = .08) ().
A multivariate analysis of variance was performed to examine whether there was a difference in behavioral profile by gender. Significant differences emerged in caregiver-rated adaptive functioning. Specifically, females (n = 9) were found to be higher functioning than males (n = 8, one parent of a male did not participate in interview) in all domains, including Communication (Female M = 73, Male M = 63; F = 11.509, p = .006), Daily Living Skills (Female M = 67, Male M = 62; F = 5.093, p = .045), and Socialization (Female M = 77, Male M = 70; F = 10.367, p = .008). Caregivers also reported significantly more behavioral concerns in males, including internalizing behaviors (F = 5.64, p = .03), externalizing behaviors (F = 4.73, p = .05), and overall maladaptive behavior (F = 5.45, p = .03). Females generally fell at the upper end of the Average range in all three areas, whereas males were consistently in the Elevated range. ().
Gender Differences in Adaptive Skills
In contrast, no gender differences were found in cognitive or visuomotor functioning.
A series of repeated measures of analysis of variance were completed to examine change over time in intellectual functioning. Two sets of analyses were completed; the first examined changes in raw scores to determine whether there were any absolute changes (i.e., intellectual development or learning), and the second examined standard or scaled scores to assess changes in relative differences (i.e., between the subjects and normative data). Change in raw scores without a corresponding change in standard scores would indicate development along a predictable trajectory, whereas change in standard scores would indicate a gain or decline in skills relative to typical patterns of development.
In overall IQ, there was significant improvement in raw scores from T1 to T2 to T3 (F = 16.213, p < .001) but not in standard scores, indicating stable overall development. In Fluid Reasoning, there was significant change evident both in raw scores (F = 9.456, p = .003) and standard scores (F = 4.334, p = .034), but the pattern of change was different; raw score change was best represented by a linear model (F = 10.284, p = .015) whereas standard score change was quadratic (F = 20.250, p = .003). Inspection of means reveals raw score gains from T1 to T2 but then a plateau in skills from T2 to T3 (see ), with the result that relative performance (standard scores) improved from mildly impaired to borderline from T1 to T2 (+0.8 SD), but then declined back to the impaired range from T2 to T3 (−0.9 SD). Significant raw score changes were evident in three of four subtests, Figure Ground (F = 16.114, p < .001), Form Completion (F = 8.972, p = .003), and Repeated Patterns (F = 6.269, p = .031, corrected via the Greenhouse-Geisser procedure for violation of sphericity). Scaled score (relative) changes were evident in two subtests, Figure Ground (F = 13.235, p = .008) and Repeated Patterns (F = 4.607, p = .029), both of which conformed to a quadratic model. Interestingly, Figure Ground raw scores (and scaled scores) declined from T1 to T2, and then increased from T2 to T3 (though the fit with a quadratic model was only slightly better than the fit with a linear model), whereas Repeated Patterns showed a profile of plateauing raw scores and increasing-then-decreasing scaled scores.
Longitudinal Pattern in Fluid Reasoning
In all of these findings, there were no significant interactions with age at time of assessment, or gender.