Very preterm children are at increased risk of reduced processing speed at 5 years of age, predicted by typical complications of prematurity and prenatal smoking.

AIM: Very little is known about risk predictors for the development of reduced processing speed, which can cause intellectual problems in later life. This study identified risk predictors at 5 years of age in a population-based cohort of very preterm infants. METHODS: Between January 2003 and August 2006, all preterm infants born before 32 weeks of gestation in Tyrol were prospectively enrolled (n = 223), and 161 underwent a detailed examination at 5 years of age, including a cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence, third edition. The processing speed quotient is calculated on the basis of two subtests that assess symbol search and coding. The association between prenatal and postnatal factors and reduced processing speed was analysed by means of logistic regression analysis. RESULTS: Of 161 children tested, 55 (34.2%) showed reduced processing speed. In 55.6% (n = 30) of these children, reduced processing speed was related to full-scale intelligence quotient scores of <85. Smoking in pregnancy, steroids for chronic lung disease and intracerebral haemorrhage predicted reduced processing speed at 5 years of age. CONCLUSION: More than a third of the very preterm children we tested showed reduced processing speed at 5 years of age, and predictors were typical complications of prematurity and smoking in pregnancy.

Don't miss patients with atypical FMR1 mutations: dysmorphism and clinical features in a boy with a partially methylated FMR1 full mutation.

UNLABELLED: Fragile X syndrome characterized by intellectual disability (ID), facial dysmorphism, and postpubertal macroorchidism is the most common monogenic cause of ID. It is typically induced by an expansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene on Xq27 to more than 200 repeats. Only rarely patients have atypical mutations in the FMR1 gene such as point mutations, deletions, or unmethylated/partially methylated full mutations. Most of these patients show a minor phenotype or even appear clinically healthy. Here, we report the dysmorphism and clinical features of a 17-year-old boy with a partially methylated full mutation of approximately 250 repeats. Diagnosis was made subsequently to the evaluation of a FMR1 premutation as the cause for maternal premature ovarian failure. Dysmorphic evaluation revealed no strikingly long face, no prominent forehead/frontal bossing, no prominent mandible, no macroorchidism, and a head circumference in the lower normal range. Acquisition of a driving license for mopeds and unaccompanied rides by public transport in his home province indicate rather mild ID (IQ = 58). CONCLUSION: This adolescent demonstrates that apart from only minor ID, patients with a partially methylated FMR1 full mutation present less to absent pathognomonic facial dysmorphism, thus emphasizing the impact of family history for a straightforward clinical diagnosis.

Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet.

This is a report on the successful treatment of a 6-year-old girl with genetically proven glucose transporter type 1 deficiency syndrome (GLUT1-DS) with modified Atkins diet (MAD). GLUT1-DS is an inborn disorder of glucose transport across the blood-brain barrier, which leads to energy deficiency of the brain with a broad spectrum of neurological symptoms including therapy-resistant epilepsy. Usually classical ketogenic diet (KD) is the standard treatment for patients with GLUT1-DS. Treatment with MAD, a variant of KD, for an observation period of 17 months resulted in improvement of seizures, alertness, cognitive abilities, and electroencephalography in this patient.

Neuropsychological profile of children after an episode of neuroborreliosis.

BACKGROUND: In the majority of patients with Lyme neuroborreliosis (LNB), neurological symptoms are transient. The extent of neuropsychological and neuropsychiatric problems in children is not well researched. OBJECTIVES: The study aimed to investigate cognitive functions and behavioral problems in children after LNB. PATIENTS AND METHODS: A total of 20 children between 6 and 16 years of age with an episode of LNB at least 4 month before neuropsychological testing were enrolled in the study and compared with 20 healthy controls. Children with LNB had cranial nerve palsies or meningoencephalitis, immunoglobulin G and immunoglobulin M antibodies for Borrelia burgdorferi in the peripheral blood, pleocytosis in the cerebrospinal fluid (leukocytes > 10 cells/µL) and/or an intrathecal synthesis of antibodies for B. burgdorferi.Neuropsychological tests assessing intellectual skills, memory, and executive functions were used. Two parental questionnaires assessing behavior, psychiatric problems, and executive functions were administered. RESULTS: Intellectual skills, memory, and executive functions of children after an episode of LNB were within the normal range. In the subcategory of working memory, children after an episode of LNB performed worse than controls. The questionnaires did not reveal behavior or psychiatric problems, although there was a tendency that children after an episode of LNB had more physical complaints. CONCLUSION: Neuropsychological deficits resulting from LNB in childhood are rare. Most children had a good cognitive, emotional, and behavioral outcome.

Brief report: CANTAB performance and brain structure in pediatric patients with Asperger syndrome.

By merging neuropsychological (CANTAB/cambridge neuropsychological test automated battery) and structural brain imaging data (voxel-based-morphometry) the present study sought to identify the neurocognitive correlates of executive functions in individuals with Asperger syndrome (AS) compared to healthy controls. Results disclosed subtle group differences regarding response speed on only one CANTAB subtest that is thought to tap fronto-executive network functions (SWM/spatial working memory). Across all participants, SWM performance was significantly associated with two brain regions (precentral gyrus white matter, precuneus grey matter), thus suggesting a close link between fronto-executive functions (SWM) and circumscribed fronto-parietal brain structures. Finally, symptom severity (ADOS total score) was best predicted by response speed on a set-shifting task (IES) thought to tap fronto-striatal functions (corrected R2 56%).

Microdeletion 19p13.2 in an almost 5-year-old boy.

Deletions of the short arm of chromosome 19 are rarely found by conventional cytogenetic techniques. This region has a high gene density and this is likely the reason why deletions in this region are associated with a severe phenotype. Since the implementation of modern high-resolution SNP- and CGH-array techniques more cases have been reported. Here, we present an almost 5-year-old boy with intellectual disability, minor dysmorphisms, febrile seizures, and a de novo deletion of 834.2 kb on 19p13.2 encompassing 32 genes. The deletion was found by the Illumina Infinium HD Human1M-Duo v1 BeadChip SNP-array and confirmed by the NimbleGen Human CGH 2.1M Whole Genome Tiling v2.0D oligonucleotide array. PCR amplification of the junction fragment and subsequent sequencing defined the breakpoints and indicated that formation was mediated by non-allelic homologous recombination (NAHR). The phenotype of our patient shows that microrearrangements even at gene-dense chromosomes may result in mild clinical consequences.

Phenotypic variability of a deletion and duplication 6q16.1 → q21 due to a paternal balanced ins(7;6)(p15;q16.1q21).

Constitutional insertional translocations are rare findings in clinical cytogenetics. Here, we report on the unbalanced segregation of a balanced paternal insertional translocation ins(7;6)(p15;q16.1q21) to three children. Investigations by conventional karyotyping, FISH with locus-specific probes, microsatellite marker analysis, and SNP-array based copy number analysis revealed a direct orientation of the inserted segment, a size of 11.3 Mb, and breakpoints between rs4370337 and rs12660854 and rs12110990 and rs4946730 on 6q16.1 and 6q21, respectively, as well as within BAC clone RP11-182J2 on 7p15. A 17-year-old daughter inherited the der(6) chromosome and was affected by severe mental retardation, obesity, and minor anomalies. Two further children inherited the der(7) chromosome. A daughter shows an almost unremarkable phenotype and only minor features in neuropsychological testing at 19 years of age. Her 14-year-old half-brother demonstrates a mild delay in cognitive development most likely jointly caused by the chromosomal rearrangement and asphyxia during delivery. The patient with the deletion confirms the previously reported phenotype of severe mental retardation and obesity in patients with del(6)(q16.2), while both patients with partial trisomy for the same segment of chromosome 6 are further examples for a generally less severe phenotype associated with duplications than with deletions, and even for the recent insight that chromosomal aneusomies of several megabases may go without major clinical consequences.

Predictive validity of attentional functions in differentiating children with and without ADHD: a componential analysis.

AIM: The objective of this study was to investigate which attentional components are of predictive utility in differentiating children with attention-deficit-hyperactivity disorder, combined type (ADHD-C) from their peers without ADHD. METHODS: Thirty-four children participated in the study: 17 males with ADHD-C (mean age 10y 4mo, SD 1y 9mo) and 17 comparison children (12 males, 5 females; mean age 10y 8mo, SD 1.7y). Attentional functions were assessed using a computer-administered, child-friendly test series in German (i.e. Testbatterie zur Aufmerksamkeitsprüfung für Kinder; KITAP). The KITAP measures several attentional components, including alertness and executive attention (inhibition, divided attention, flexibility). RESULTS: The variable best able to discriminate between children with and without ADHD-C was found to be response time variability in a go/no go task, followed by, in order, number of errors in a divided attention task and response time variability in an alertness task. However, group discrimination was not facilitated by differences in either response latency or accuracy of response in visuospatial attention and attentional flexibility tasks. INTERPRETATION: The assessment of attentional functions proved to be a powerful instrument for discriminating between children with and without ADHD-C. Notably, the discriminative power of executive attention was found to be task dependent and dependent on processing demands.