Cognitive ability predicts degree of genetic abnormality in participants with 18q deletions

Abstract

One of the most common chromosomal deletions is a loss of genetic material from the long arm of chromosome 18. Most individuals with this condition exhibit mental retardation (68%), yet previous attempts to link cognitive status to deletion size have not shown an association, possibly because cases with additional genetic abnormalities were included. We studied 46 participants ranging from 3 to 35 years of age who had a pure genetic abnormality by excluding those with mosaicism or complex genetic rearrangements. Our patients had terminal deletions ranging from a proximal breakpoint at 18q21.1 (greater genetic abnormality, larger deletion size) to a more distal breakpoint at 18q23 characterized with molecular genetic techniques. Cognitive ability, assessed with the age-appropriate measure (Bayley, 1993, Differential Ability Scale, Wechsler Scales), ranged from IQ 5 49 to 113, with a predominance of mild and moderate mental retardation. Using multivariate regression, deletion size breakpoint rank order was predicted by cognitive ability, age, and adaptive behavior (Vineland Adaptive Behavior Scales), accounting for 36% of the variance in deletion size. However, lower cognitive ability (beta 5 .34, p 5 .032) and younger age (beta 5 .296, p 5 .024) predicted a larger deletion size, but adaptive behavior (beta 5 .225, p 5 .15) did not. An additional multivariate regression showed that cognitive ability and age together accounted for 33% of the variance in deletion size, whereas univariate regression showed that cognitive ability accounted for 26% of the variance and age accounted for 11% of the variance. These findings suggest that degree of cognitive impairment is associated with genetic abnormality when a large sample of individuals with "pure" deletions of genetic material from chromosome 18 is examined. (JINS, 2005, 11, 584-590.)

Psychiatric syndromes in individuals with chromosome 18 abnormalities

“…Although less systematically studied, many subjects with chromosome 18 abnormalities also manifest neuropsychiatric symptoms. Mental retardation is found in case reports of all three abnormalities (18p-, 18q-, and 18p tetrasomy), and in one study was estimated at 68% of all 18q deletion subjects [Semrud-Clikeman et al, 2005]. Abnormal EEG findings and epilepsy have been described in case reports for all three chromosomal disorders [Chudley et al, 1974;Wilson et al, 1979;Wilson and Al Saadi, 1989;Schinzel et al, 1991;Chudley et al, 1992;Krasikov et al, 1992;Poissonnier et al, 1992;Engelen et al, 1998;Tinkle et al, 2003;Linnankivi et al, 2006;Swingle et al, 2006;Brenk et al, 2007;Cody et al, 2007].…”

Prenatal Diagnosis of 18q-Syndrome: A Case of Fetal Mosaicism with a Normal Karyotype in Chorionic Villi

“…It may be hypothesized that the cytogenetically and functionally normal placenta, as in the present case, can account for the normal weight of a fetus with a karyotype anomaly usually associated with intrauterine growth retardation [12] .…”

Global brain dysmyelination with above-average verbal skills in 18q - syndrome with a 17 Mb terminal deletion

“…Thus, our patient has one of the largest terminal 18q deletions reported in an individual without mental retardation. Unfortunately, two previous studies evaluating the neuropsychiatry and neuropsychology of 18q) syndrome do not specify chromosomal breakpoints and IQ scores of individual patients, so it is not possible to compare our findings directly with these reports (4,9).…”

“…Mental retardation is reported in the majority of patients, but exact neuropsychological test results are available in very few cases only. A recent study suggests that the degree of cognitive impairment is related to the amount of missing genetic material in individuals with deletions in 18q (4). However, individuals have been described, all of whom carried 18q deletions with breakpoints in 18q22, Background -Patients with the karyotypic finding of a terminal deletion in the long arm of chromosome 18 (18q) syndrome) commonly display cerebral dysmyelination and developmental delay.…”

“…Neurological symptoms include seizures, hypotonia, oculomotor problems, nystagmus, tremor, poor coordination, choreiform movements, and poor cerebral myelination as determined by magnetic resonance imaging (MRI) of the brain (3). A recent study suggests that the degree of cognitive impairment is related to the amount of missing genetic material in individuals with deletions in 18q (4). A recent study suggests that the degree of cognitive impairment is related to the amount of missing genetic material in individuals with deletions in 18q (4).…”