Cerebroretinal microangiopathy with calcifications and cysts associated with CTC1 and NDP mutations.

Mutations in the conserved telomere maintenance component 1 (CTC1) gene were recently described in Coats plus syndrome and in cerebroretinal microangiopathy with calcifications and cysts. Norrie disease protein (NDP) gene was found mutated in Norrie disease, in Familial Exudative Vitreoretinopathy, and in Coats syndrome. Here we describe a boy affected by Norrie disease who developed typical features of cerebroretinal microangiopathy with calcifications and cysts.

The ability of CBCL DSM-oriented scales to predict DSM-IV diagnoses in a referred sample of children and adolescents.

The majority of studies examining associations between clinical-diagnostic and empirical-quantitative approaches have concentrated only on the target diagnosis without taking into account any possible co-variation of psychopathological traits, which is intrinsic to child psychopathology. The ability of child behaviour checklist (CBCL) DSM-oriented scales (DOSs) to predict target and other DSM diagnoses, taking into consideration the covariation of psychopathological traits, was analysed by logistic regression analysis. Corresponding odds ratio (OR) was used as indicator of the strength of the relationship between the clinical score in DOSs and the presence of DSM-IV diagnoses.

Eye-hand coordination in children with high functioning autism and Asperger's disorder using a gap-overlap paradigm.

We investigated eye-hand coordination in children with autism spectrum disorders (ASD) in comparison with age-matched normally developing peers. The eye-hand correlation was measured by putting fixation latencies in relation with pointing and key pressing responses in visual detection tasks where a gap-overlap paradigm was used and compared to fixation latencies in absence of manual response. ASD patients showed less efficient eye-hand coordination, which was particularly evident when pointing towards a target was being fixated.

Psychopathology and adversities from early- to late-adolescence: a general population follow-up study with the CBCL DSM-Oriented Scales.

Aims. Adolescence is a critical transition phase between childhood and adulthood, when the burden of mental disorder may still be prevented. The aim of this study was to evaluate the continuity and discontinuity of behavioural problems in adolescence while taking into account the multiple co-variation of psychopathological traits and the complex role of recent stressful life events (SLEs).

A novel mutation in the β-tubulin gene TUBB2B associated with complex malformation of cortical development and deficits in axonal guidance.

Neurological disorders characterized by abnormal neuronal migration, organization, axon guidance, and maintenance have recently been associated with missense and splice-site mutations in the genes encoding α- and β-tubulin isotypes TUBA1A, TUBB2B, TUBB3, and TUBA8. We found a novel heterozygous mutation c.419G > C in exon 4 of the gene encoding TUBB2B in a female with microcephaly, agenesis of the corpus callosum, open-lip schizencephaly of the left parietal lobe, extensive polymicrogyria, basal ganglia and thalami dysmorphisms, and vermis and right third nerve hypoplasia.

GTP-dependent packing of a three-helix bundle is required for atlastin-mediated fusion.

The mechanisms governing atlastin-mediated membrane fusion are unknown. Here we demonstrate that a three-helix bundle (3HB) within the middle domain is required for oligomerization. Mutation of core hydrophobic residues within these helices inactivates atlastin function by preventing membrane tethering and the subsequent fusion.

Further evidence of complex motor dysfunction in drug naive children with autism using automatic motion analysis of gait.

In order to increase the knowledge of locomotor disturbances in children with autism, and of the mechanism underlying them, the objective of this exploratory study was to reliably and quantitatively evaluate linear gait parameters (spatio-temporal and kinematic parameters), upper body kinematic parameters, walk orientation and smoothness using an automatic motion analyser (ELITE systems) in drug naïve children with Autistic Disorder (AD) and healthy controls. The children with AD showed a stiffer gait in which the usual fluidity of walking was lost, trunk postural abnormalities, highly significant difficulties to maintain a straight line and a marked loss of smoothness (increase of jerk index), compared to the healthy controls. As a whole, these data suggest a complex motor dysfunction involving both the cortical and the subcortical area or, maybe, a possible deficit in the integration of sensory-motor information within motor networks (i.

Neurological soft signs feature a double dissociation within the language system in Williams syndrome.

The neurocognitive profile of Williams-Beuren syndrome (WBS) is characterized by visuospatial deficits, apparently fluent language, motor soft signs, and hypersociability. We investigated the association between neuromotor soft signs and visuospatial, executive-attentive, mnestic and linguistic functions in a group of 26 children and young adults with WBS. We hypothesized that neurological soft signs could be an index of subtle neurofunctional deficits and thus provide a behavioural window into the processes underlying neurocognition in Williams-Beuren syndrome.

COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10-14.

The functional Val158Met COMT polymorphism appears to affect a host of behaviours mediated by the pre-frontal cortex, and has been found associated to the risk for disruptive behaviours including ADHD. Parental socioeconomic status (SES) has also been reported as a predictor for the same childhood disorders. In a general population sample of 575 Italian pre-adolescents aged 10-14, we examined the association of the functional Val158Met COMT polymorphism and SES-both as linear and interactive effects-with oppositional defiant problems, conduct problems, and attention deficit/hyperactivity problems, as defined by the newly established Child Behaviour Check-List/6-18 DSM oriented scales.

Evidence for a link among cognition, language and emotion in cerebellar malformations.

We compared the neurobehavioral profiles of children with Joubert syndrome (JS participants), a rare autosomal recessive condition characterized on magnetic resonance imaging (MRI) by hypoplasia of the cerebellar vermis and midbrain-hindbrain malformations, and children with malformations confined to the cerebellar vermis and one or both hemispheres (Cerebellar malformations--CM participants). We aimed at investigating the influence of anatomo-clinical similarities (vermian malformation) and differences (intact cerebellar hemispheres vs sparing of the pons, respectively) with respect to cognitive, linguistic and emotional development, assuming as a reference framework the Cerebellar Cognitive Affective Syndrome (CCAS). Results show that severe to moderate mental retardation is infrequent in JS children, while it is present in more than half the sample of CM children.

Complex segmental duplications mediate a recurrent dup(X)(p11.22-p11.23) associated with mental retardation, speech delay, and EEG anomalies in males and females.

Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.

The role played by the interaction between genetic factors and attachment in the stress response in infancy.

Background: The importance of understanding which environmental and biological factors are involved in determining individual differences in physiological response to stress is widely recognized, given the impact that stress has on physical and mental health.

Methods: The child-mother attachment relationship and some genetic polymorphisms (5-HTTLPR, COMT and GABRA6) were tested as predictors of salivary cortisol and alpha amylase concentrations, two biomarkers of hypothalamic-pituitary-adrenocortical (HPA) axis and sympathetic adrenomedullary (SAM) system activity, during the Strange Situation (SS) procedure in a sample of more than 100 healthy infants, aged 12 to 18 months.

Results: Individual differences in alpha amylase response to separation were predicted by security of attachment in interaction with 5-HTTLPR and GABRA6 genetic polymorphisms, whereas alpha amylase basal levels were predicted by COMT x attachment interaction.

Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin.

Establishment and maintenance of proper architecture is essential for endoplasmic reticulum (ER) function. Homotypic membrane fusion is required for ER biogenesis and maintenance, and has been shown to depend on GTP hydrolysis. Here we demonstrate that Drosophila Atlastin--the fly homologue of the mammalian GTPase atlastin 1 involved in hereditary spastic paraplegia--localizes on ER membranes and that its loss causes ER fragmentation.

The influence of family structure, the TPH2 G-703T and the 5-HTTLPR serotonergic genes upon affective problems in children aged 10-14 years.

Background: Both genetic and psychosocial risk factors influence the risk for depression in development. While the impacts of family structure and of serotonergic polymorphisms upon individual differences for affective problems have been investigated separately, they have never been considered together in a gene-environment interplay perspective.

Methods: We examined the effects of family structure and two serotonergic polymorphisms (the TPH2 G-703T and the 5-HTTLPR) upon depressive symptoms assessed by the new CBCL/6-18 DSM-oriented Affective Problems scale in a general population sample of 607 Italian children aged 10-14 years.

Mosaic 22q13 deletions: evidence for concurrent mosaic segmental isodisomy and gene conversion.

Although 22q terminal deletions are well documented, very few patients with mosaicism have been reported. We describe two new cases with mosaic 22q13.2-qter deletion, detected by karyotype analysis, showing the neurological phenotype of 22q13.

Socioeconomic status mediates the genetic contribution of the dopamine receptor D4 and serotonin transporter linked promoter region repeat polymorphisms to externalization in preadolescence.

The impact of socioeconomic status (SES) and genetic polymorphisms on individual differences for externalized behaviors have often been investigated separately in studies of children and adults. In a general population sample of 607 Italian preadolescents, we examined the independent and joint effects of SES and the dopamine receptor D4 (DRD4) and serotonin transporter linked promoter region (5-HTTLPR) polymorphisms upon rule-breaking and aggressive behaviors measured with the Child Behavior CheckList/6-18. We found evidence, which was based on both one locus and two-loci genotype analyses, that low SES and DRD4 long and 5-HTTLPR long alleles, both alone and in interaction, are associated with higher aggressive behavior scores.

An assessment of transmission disequilibrium between quantitative measures of childhood problem behaviors and DRD2/Taql and DRD4/48bp-repeat polymorphisms.

In a pilot study of 120 children with reading disabilities, we assessed the presence of linkage and association between the DRD2/Taql and the DRD4/48bp-repeat polymorphisms and quantitative measures of behavioral problems derived from parental rated Child Behavior Checklist (CBCL) [Achenbach, T. M. (1991).

A case-control and family-based association study of the 5-HTTLPR in pediatric-onset depressive disorders.

Background: Pediatric depression can be particularly informative for clarification of the causes of mood disorders. The aim of this work was to explore the possible association between childhood- and early-adolescent-onset DSM-IV depressive disorders (DD; including major depression and dysthymia) and the serotonin transporter-linked promoter polymorphism (5-HTTLPR) locus.

Methods: The case-control sample consisted of 68 unrelated patients with DD, and 68 unrelated age- and gender-matched healthy control subjects.

Unilateral periventricular nodular heterotopia associated with diffuse areas of cerebral functional abnormalities.

A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic resonance imaging revealed a unilateral periventricular nodular heterotopia near the occipital ventricular right horn. Interictal and ictal electroencephalographic recordings showed bilateral specific epileptiform anomalies in the occipital region and asynchronous slow waves in frontal areas.