Neuropsychological and ASD phenotypes in rare genetic syndromes: A critical review of the literature.

OBJECTIVE: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by core deficits in social communication and restricted and repetitive behaviors and interests. Recent advances in clinical genetics have improved our understanding of genetic syndromes associated with ASD, which has helped clarify distinct etiologies of ASD and document syndrome-specific profiles of neurocognitive strengths and weaknesses. Pediatric neuropsychologists have the potential to be impactful members of the care team for children with genetic syndromes and their families. METHOD: We provide a critical review of the current literature related to the neuropsychological profiles of children with four genetic syndromes associated with ASD, including Tuberous Sclerosis Complex (TSC), fragile X syndrome (FXS), 22q11.2 deletion syndrome, and Angelman syndrome. Recommendations for assessment, intervention, and future directions are provided. RESULTS: There is vast heterogeneity in terms of the cognitive, language, and developmental abilities of these populations. The within- and across-syndrome variability characteristic of genetic syndromes should be carefully considered during clinical evaluations, including possible measurement limitations, presence of intellectual disability, and important qualitative differences in the ASD-phenotypes across groups. CONCLUSIONS: Individuals with genetic disorders pose challenging diagnostic and assessment questions. Pediatric neuropsychologists with expertise in neurodevelopmental processes are well suited to address these questions and identify profiles of neurocognitive strengths and weaknesses, tailor individualized recommendations, and provide diagnostic clarification.

Outcomes of Cataract Surgery Complicated by Retained Lens Fragments Requiring Pars Plana Vitrectomy.

OBJECTIVE: To analyze outcomes and complications related to cataract surgery complicated by retained lens fragment (RLF) requiring pars plana vitrectomy (PPV) in a county hospital where procedures are performed by trainees. METHODS: Retrospective study of consecutive patients who met inclusion criteria and underwent PPV for RLF in the vitreous cavity at an urban teaching hospital between January 2010 and January 2016 (N=20). MAIN OUTCOMES/MEASURES: Visual acuity was recorded pre- and post-operatively over a follow-up period of 3 to 12 months. Complications and patient factors contributing to outcomes were assessed using paired and unpaired t-tests and multiple linear regression. RESULTS: The average rate of cataract surgery with RLF requiring PPV was 0.75%. Twenty patients met inclusion criteria. Mean pre-operative visual acuity (VA) was logMAR 1.7 (Snellen 20/1000). Nearly half (8/20) had nuclear cataracts grade 3+ or higher. The majority (14/20) had factors predisposing them to cataract surgery complications. Most patients underwent PPV within 1 week (median 6.5 days). At 12-month follow-up, significant (p=0.001) visual acuity (VA) improvement from initial VA was observed, with final mean logMAR 0.6 (± 0.75; Snellen 20/80) and median logMAR 0.35 (Snellen 20/45). Nearly half of the patients had a final Snellen VA ≥20/40. Factors associated with less VA improvement were older age and greater proportion of lens dropped (p<0.01). Complications following PPV included hypotony (5 patients), corneal edema (4), elevated intraocular pressure (IOP) (3), and cystoid macular edema (3). CONCLUSIONS/RELEVANCE: Despite patients with advanced pathology and trainee surgeons, rates of cataract surgery-associated RLF requiring PPV at a large tertiary care teaching hospital are similar to reported rates in the literature.

Antecedents of Screening Positive for Attention Deficit Hyperactivity Disorder in Ten-Year-Old Children Born Extremely Preterm.

BACKGROUND: The incidence of attention deficit hyperactivity disorder is higher among children born very preterm than among children who are mature at birth. METHODS: We studied 583 ten-year-old children who were born before 28 weeks of gestation whose IQ was above 84 and had a parent-completed Child Symptom Inventory-4, which allowed classification of the child as having or not having symptoms of attention deficit hyperactivity disorder. For 422 children, we also had a teacher report, and for 583 children, we also had a parent report of whether or not a physician made an attention deficit hyperactivity disorder diagnosis. RESULTS: The risk profile of screening positive for attention deficit hyperactivity disorder based on a parent's report differed from the risk profile based on the teacher's report, whereas the risk profile according to a physician and according to any two observers closely resembled the parent-reported profile. Among the statistically significant risk factors were young maternal age (parent, physician, and two observers), maternal obesity (parent, physician, and two observers), maternal smoking (parent, physician, and two observers), magnesium given at delivery for seizure prophylaxis (parent and two observers), recovery of Mycoplasma sp. from the placenta (teacher and two observers), low gestational age (parent and two observers), low birth weight (teacher and physician), singleton (parent, physician, and two observers), male (parent, teacher, physician, and two observers), mechanical ventilation on postnatal day seven (physician), receipt of a sedative (parent and two observers), retinopathy of prematurity (parent), necrotizing enterocolitis (physician), antibiotic receipt (physician and two observers), and ventriculomegaly on brain scan (parent and two observers). CONCLUSIONS: The multiplicity of risk factors identified can be subsumed as components of four broad themes: low socioeconomic state, immaturity or vulnerability, inflammation, and epigenetic phenomena.

Observer variability identifying attention deficit/hyperactivity disorder in 10-year-old children born extremely preterm.

AIM: A DSM-5 diagnosis of attention deficit/hyperactive disorder (ADHD) requires that symptoms be present in two settings. We wanted to see how teachers and parents compare on their assessments. METHODS: We evaluated how well Child Symptom Inventory-4 (CSI-4) reports from 871 parents and 634 teachers of 10-year-old children born before the 28th week of gestation provided information about indicators of school dysfunction. RESULTS: Kappa values for parent and teacher agreement of any ADHD were at best fair to poor (<0.41). Nevertheless, ADHD identified by each alone provided a moderate amount of information about such indicators of school dysfunction as grade repetition. Only occasionally did agreement provide more information than provided by only one reporter. Mother's social class and intelligence level did not discriminate between parents who did and did not agree with the teacher. CONCLUSION: ADHD identified by a single observer can provide appreciable information about a range of the child's functions needed for success in school and, therefore, should not be discounted when another observer does not consider the child to have ADHD symptoms.

Neurocognitive Correlates of Attention-Deficit Hyperactivity Disorder Symptoms in Children Born at Extremely Low Gestational Age.

OBJECTIVE: Compared with children born near term, those born extremely preterm (EP) are at much higher risk for attention-deficit hyperactivity disorder (ADHD). Little information is available about differences in neuropsychological outcomes among EP children with and without ADHD. Our analyses aimed to evaluate the neuropsychological correlates of ADHD symptoms in extremely low gestational age newborns (ELGANs). METHODS: We obtained Child Symptom Inventory-4 reports from parents (n = 871) and teachers (n = 634) of 10-year-old children born before the 28th week of gestation. Participants completed standardized assessments of neurocognitive and academic functioning. RESULTS: In the total sample, children who screened positive for ADHD symptoms were at increased risk for neurocognitive limitations. These associations were weaker when the sample was limited to those with intelligence quotient (IQ) ≥70 or ≥85. Even those with IQ ≥85 who screened positive for ADHD symptoms were more likely than their peers to have deficits on the DAS-II Working Memory Cluster and the NEPSY-II Auditory Response subtest. The risks for impaired academic performance (Z ≤ -1) on components of the WIAT-III were 2-to-3 times higher in this group than among ELGANs not classified as having ADHD symptoms. CONCLUSION: Among children born EP, those with ADHD symptoms are more likely to have global neurocognitive impairment. When IQ is within normal limits, ADHD symptoms are associated with deficits in executive functioning skills. These findings highlight a group at risk for executive functioning deficits and related academic difficulties, even in the absence of intellectual disability.

Systemic Inflammation during the First Postnatal Month and the Risk of Attention Deficit Hyperactivity Disorder Characteristics among 10 year-old Children Born Extremely Preterm.

Although multiple sources link inflammation with attention difficulties, the only human study that evaluated the relationship between systemic inflammation and attention problems assessed attention at age 2 years. Parent and/or teacher completion of the Childhood Symptom Inventory-4 (CSI-4) provided information about characteristics that screen for attention deficit hyperactive disorder (ADHD) among 793 10-year-old children born before the 28th week of gestation who had an IQ ≥ 70. The concentrations of 27 proteins in blood spots obtained during the first postnatal month were measured. 151 children with ADHD behaviors were identified by parent report, while 128 children were identified by teacher report. Top-quartile concentrations of IL-6R, TNF-α, IL-8, VEGF, VEFG-R1, and VEGF-R2 on multiple days were associated with increased risk of ADHD symptoms as assessed by a teacher. Some of this increased risk was modulated by top-quartile concentrations of IL-6R, RANTES, EPO, NT-4, BDNF, bFGF, IGF-1, PIGF, Ang-1, and Ang-2. Systemic inflammation during the first postnatal month among children born extremely preterm appears to increase the risk of teacher-identified ADHD characteristics, and high concentrations of proteins with neurotrophic properties appear capable of modulating this increased risk.

Behavior disorders in extremely preterm/extremely low birth weight children in kindergarten.

OBJECTIVE: To examine the prevalence of behavior disorders in a 2001-2003 birth cohort of extremely preterm/extremely low birth weight (EPT/ELBW, <28 weeks gestational age or <1000 g) children in kindergarten. METHOD: We compared 148 EPT/ELBW children with 111 term-born normal birth weight classmate controls on reports of psychiatric symptoms obtained from parent interview (Children's Interview for Psychiatric Syndromes-Parent Form [P-ChIPS]), parent and teacher ratings of behavior (Child Behavior Checklist, Teacher's Report Form, and Behavior Rating Inventory of Executive Function), and teacher ratings of social functioning (School Social Behavior Scales, second edition). Associations of behavior disorders with global cognitive ability and tests of executive function were also examined within the EPT/ELBW group. RESULTS: Rates of attention-deficit/hyperactivity disorder combined on psychiatric interview were about twice as high for the EPT/ELBW group than for the normal birth weight group, odds ratio (95% confidence interval) = 2.50 (1.34, 4.68), p = .004. The EPT/ELBW group also had much higher rates of teacher-identified disorders in attention, behavior self-regulation, and social functioning, with odds ratios (95% confidence intervals) ranging from 3.35 (1.64, 6.83) to 18.03 (4.12, 78.94), all p values <.01. Attention-deficit/hyperactivity disorder and impaired behavior self-regulation were associated with deficits on tests of executive function but not with global cognitive impairment. CONCLUSIONS: The findings document increased rates of disorders in attention, behavior self-regulation, and socialization in EPT/ELBW children and suggest that deficits on tests of executive function are associated with some of these disorders. Early identification and intervention for these disorders are needed to promote early adjustment to school and facilitate learning progress.

Neurocognitive profile in a case of maple syrup urine disease.

Maple Syrup Urine Disease (MSUD) is a metabolic disease with associated enzyme deficiency and an inability to break down amino acids. Neurotoxic levels can occur resulting in neurological sequelae. Information regarding cognitive functions has suggested greater verbal than visuospatial abilities. Specific neuropsychological functions have not been studied. The objective of this study is to examine the neuropsychological profile in a case of MSUD. We present a case study of a 7-year-old female who has a history of late diagnosis (7 days of age) and poor metabolic control. Consistent with existing literature, a profile of stronger verbal reasoning and memory skills compared with visual-perceptual and nonverbal memory was revealed. Additional weaknesses were demonstrated with attention, emerging executive functions, and fine motor control. The results suggest that while previously described nonverbal reasoning and visuospatial impairments are present, there is likely a more complex pattern of neuropsychological impairments in children with MSUD, especially those with poor metabolic control.