Childhood predictors of written expression in late adolescents with 22q11.2 deletion syndrome: a longitudinal study.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is the second most prevalent genetic syndrome and has a characteristic academic and behavioural phenotype. The primary objective of the current study was to examine the childhood predictors of written expression achievement in adolescents with 22q11DS. Written expression is an important skill that can impact an individual's overall academic performance, potentially resulting in increased levels of stress and exacerbation of psychiatric symptoms. METHODS: A total of 119 participants were included in this study. Sixty-nine late adolescents with 22q11DS and 50 controls (consisting of a combined sample of 23 unaffected siblings of youth with 22q11DS and 27 community controls) participated in a 6-year longitudinal research project and received neuropsychological test batteries every 3 years. The Written Expression subtest of the Wechsler Individual Achievement Test - Second Edition was the primary outcome measure in the current project. RESULTS: Findings indicated differences in childhood predictors of adolescent written expression between participants in the 22q11DS group and participants in the control group. Whereas childhood verbal IQ scores predicted adolescent written expression for participants in the control group, childhood executive function and language skills were unique predictors of adolescent written expression in individuals with 22q11DS. CONCLUSIONS: Childhood predictors of late adolescent written expression in 22q11DS differ in meaningful ways from predictors in the non-22q11DS population. These results offer some guidance on the underlying factors that may be useful to consider when developing written expression interventions for children with 22q11DS.

Neurocognitive and familial moderators of psychiatric risk in velocardiofacial (22q11.2 deletion) syndrome: a longitudinal study.

BACKGROUND: Although risk for psychosis in velocardiofacial (22q11.2 deletion) syndrome (VCFS) is well established, the cognitive and familial factors that moderate that risk are poorly understood. METHOD: A total of 75 youth with VCFS were assessed at three time points, at 3-year intervals. Time 1 (T1) psychiatric risk was assessed with the Behavior Assessment System for Children (BASC). Data reduction of BASC scores yielded avoidance-anxiety and dysregulation factors. Time 2 (T2) neuropsychological and family function and time 3 (T3) prodromal/overt psychosis were assessed. Poisson regression models tested associations between T3 positive prodromal symptoms/overt psychosis and T1 psychiatric risk, T2 cognitive and familial factors, and their interactions. RESULTS: T1 avoidance-anxiety ratings predicted T3 prodromal/overt psychosis. T2 verbal learning scores moderated this association, such that individuals with low avoidance-anxiety scores and stronger verbal learning skills were the least likely to demonstrate prodromal/overt psychosis at T3. Low scores on a T2 visual vigilance task also predicted T3 prodromal/overt psychosis, independently of the effect of T1 avoidance-anxiety scores. T1 dysregulation scores did not predict T3 prodromal/overt psychosis in a linear manner. Instead, the association between dysregulation and prodromal/overt psychosis was amplified by T2 levels of family organization, such that individuals with low dysregulation scores and low family organization scores were the most likely to exhibit T3 prodromal/overt psychosis. CONCLUSIONS: Significant moderators of psychiatric risk in VCFS include verbal learning skills as well as levels of family organization, carrying implications for early identification and preventative treatment of youth with VCFS at highest risk for psychosis.

Predicting reading comprehension academic achievement in late adolescents with velo-cardio-facial (22q11.2 deletion) syndrome (VCFS): a longitudinal study.

BACKGROUND: The primary objective of the current study was to examine the childhood predictors of adolescent reading comprehension in velo-cardio-facial syndrome (VCFS). Although much research has focused on mathematics skills among individuals with VCFS, no studies have examined predictors of reading comprehension. METHODS: 69 late adolescents with VCFS, 23 siblings of youth with VCFS and 30 community controls participated in a longitudinal research project and had repeat neuropsychological test batteries and psychiatric evaluations every 3 years. The Wechsler Individual Achievement Test-2nd edition (WIAT-II) Reading Comprehension subtest served as our primary outcome variable. RESULTS: Consistent with previous research, children and adolescents with VCFS had mean reading comprehension scores on the WIAT-II, that were approximately two standard deviations below the mean and word reading scores approximately one standard deviation below the mean. A more novel finding is that relative to both control groups, individuals with VCFS demonstrated a longitudinal decline in reading comprehension abilities yet a slight increase in word reading abilities. In the combined control sample, WISC-III FSIQ, WIAT-II Word Reading, WISC-III Vocabulary and CVLT-C List A Trial 1 accounted for 75% of the variance in Time 3 WIAT-II Reading Comprehension scores. In the VCFS sample, WISC-III FSIQ, BASC-Teacher Aggression, CVLT-C Intrusions, Tower of London, Visual Span Backwards, WCST Non-perseverative Errors, WIAT-II Word Reading and WISC-III Freedom from Distractibility index accounted for 85% of the variance in Time 3 WIAT-II Reading Comprehension scores. A principal component analysis with promax rotation computed on the statistically significant Time 1 predictor variables in the VCFS sample resulted in three factors: Word reading decoding/Interference control, Self-Control/Self-Monitoring and Working Memory. CONCLUSIONS: Childhood predictors of late adolescent reading comprehension in VCFS differ in some meaningful ways from predictors in the non-VCFS population. These results offer some guidance for how best to consider intervention efforts to improve reading comprehension in the VCFS population.

Executive functioning in high-IQ adults with ADHD.

BACKGROUND: To examine the association between psychological tests of executive functioning and functional outcomes among high-IQ adults with attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were high-IQ adults with (n=64) and without ADHD (n=53). Subjects were administered a battery of neuropsychological tests assessing executive functioning. RESULTS: High-IQ adults with ADHD performed less well than those without ADHD on several psychological tests of executive functioning, including the Wisconsin Card Sorting Test (WCST), Stroop Color and Word Test, Rey-Osterrieth Complex Figure Test (ROCF), California Verbal Learning Test (CVLT) and an auditory continuous performance test (CPT). Test performance in the high-IQ adult ADHD group, however, was average. In the entire sample, performance on several tests of executive functioning including the ROCF and the CVLT were significant predictors of real-world functioning. CONCLUSIONS: High-IQ adults with ADHD perform less well on tests of executive functioning relative to high-IQ control participants. Performance on several tests of executive functioning was a significant predictor of functioning.

Is adult attention deficit hyperactivity disorder a valid diagnosis in the presence of high IQ?

BACKGROUND: Because the diagnosis of attention deficit hyperactivity disorder (ADHD) in higher education settings is rapidly becoming a contentious issue, particularly among patients with high IQs, we sought to assess the validity of diagnosing ADHD in high-IQ adults and to further characterize the clinical features associated with their ADHD. METHOD: We operationalized high IQ as having a full-scale IQ120. We identified 53 adults with a high IQ who did not have ADHD and 64 adults with a high IQ who met diagnostic criteria for ADHD. Groups did not differ on IQ, socio-economic status or gender. RESULTS: High-IQ adults with ADHD reported a lower quality of life, had poorer familial and occupational functioning, and had more functional impairments, including more speeding tickets, accidents and arrests. Major depressive disorder, obsessive-compulsive disorder and generalized anxiety disorder diagnoses were higher in high-IQ adults with ADHD. All other psychiatric co-morbidities, including antisocial personality disorder and substance abuse, did not differ between the two high-IQ groups. ADHD was more prevalent in first-degree relatives of adults with ADHD relative to controls. CONCLUSIONS: Our data suggest that adults with ADHD and a high IQ display patterns of functional impairments, familiality and psychiatric co-morbidities that parallel those found in the average-IQ adult ADHD population.

Temperament in velocardiofacial syndrome.

BACKGROUND: Velocardiofacial syndrome (VCFS) is a microdeletion syndrome caused by a 22q11.2 chromosomal deletion. METHODS: In this study, parents reported on their own temperament as well as the temperament of their child. Sixty-seven children with VCFS (mean age = 10.8, SD = 2.8; range 6-15), and age-, race- and gender-ratio matched samples of 47 community control participants (mean age = 10.4, SD = 2.6; range 6-15), and 18 sibling control participants (mean age = 12.1, SD = 1.9; range 9-15) took part in the current project. RESULTS: Children with VCFS have a temperament that may best be described as modestly difficult; while participants with VCFS were not more difficult across all temperamental domains, children with VCFS were rated by their parents as being: (1) less regular in their daily habits (e.g. eating at the same time each day, etc.); (2) less able to focus/sustain attention; (3) less cheerful/pleasant; (4) less likely to stay with an activity for a long time; and (5) less able to respond flexibly to changes in the environment. CONCLUSIONS: The best predictors of parent report of behavioural symptoms in children with VCFS were poor concordance between parent and child temperament across general activity level and mood domains.

Normal cognition and behavior in a Smith-Lemli-Opitz syndrome patient who presented with Hirschsprung disease.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis. It is caused by mutations in the gene encoding the enzyme 7-dehydrocholesterol Delta7-reductase (DHCR7), which catalyzes the final step in cholesterol biosynthesis, usually resulting in cholesterol deficiency. We report a 3.5-year-old girl who has cognition in the low average range and normal behavior, but in whom molecular studies identified two missense mutations in DHCR7: V326L and F284L. She was born at term following an uncomplicated pregnancy and delivery, and presented at 12 days of age with poor feeding, abdominal distention, and jaundice. Colonic biopsy was consistent with Hirschsprung disease. On physical examination she had mild ptosis, a long philtrum, mild micrognathia, a short, upturned nose, and subtle 2,3 syndactyly. Her 7-dehydrocholesterol (7-DHC) level was markedly elevated at 8.7 mg/dl (normal 0.10 +/- 0.05), and her cholesterol level was normal at 61 mg/dl (normal for newborn period 50-80 mg/dl). Karyotype analysis was normal, 46,XX. Breast milk feeding was initiated and continued for 18 months. Cholesterol supplementation was implemented at 100 mg/kg/day at 3 months, which resulted in increased cholesterol levels and reduced dehydrocholesterol levels. Neuropsychological testing has shown functioning in the low average range, between the 14th and 18th centiles when compared to peers. This is markedly higher than most children with SLOS. She has no behavioral problems. MRI and MRS testing of the brain revealed no structural abnormalities. This is in contrast to a recently reported case by Prasad et al. [2002: Am J Med Genet 108:64-68] with a mild phenotype, behavioral problems, and abnormal MRI, who is compound heterozygote for both a null and missense mutation. Our case suggests that patients with severe feeding disorders with or without Hirschprung disease and postnatal onset microcephaly may warrant screening for SLOS.