Proopiomelanocortin (POMC) sequencing and developmental delay: Preliminary evidence for a SNP in the 3' UTR region of the POMC gene-Possible relevance for biological risk and self-injurious behavior.

The proopiomelanocortin (POMC) molecule has been implicated in models of self-injurious behavior (SIB) in neurodevelopmental disorders, but it has never been specifically sequenced in search of base specific polymorphisms. The empirical focus of this preliminary study was to sequence the POMC gene in 11 children (mean age = 41.8 months, range = 12-60 months; 73% male) with clinical concerns regarding global developmental delay, 5 with reported self-injury.

A Case-Controlled Investigation of Tactile Reactivity in Young Children With and Without Global Developmental Delay.

Assessing tactile function among children with intellectual, motor, and communication impairments remains a clinical challenge. A case control design was used to test whether children with global developmental delays (GDD; n = 20) would be more/less reactive to a modified quantitative sensory test (mQST) compared to controls (n = 20). Reactivity was indexed by blinded behavioral coding across vocal, facial, and gross motor responses during the mQST.

A Direct Comparison of Self-Injurious and Stereotyped Motor Behavior Between Preschool-Aged Children With and Without Developmental Delays.

Objective: To compare the prevalence of self-injurious behavior (SIB) and stereotyped motor behavior (STY) of preschool-aged children with developmental delays (DD group) and their peers without developmental delays (TD group) using a standardized caregiver report scale.

Methods: The Repetitive Behavior Scale-Revised was completed by caregivers of children with developmental delays and their peers without developmental delays. Frequency of occurrence and severity ratings for SIB and STY were compared between groups.

Peripheral Innervation in Children With Global Developmental Delay: Biomarker for Risk for Self-Injurious Behavior?

The relation between somatosensory mechanisms and self-injury among children with neurologic impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.

Refining analyses of copy number variation identifies specific genes associated with developmental delay.

Copy number variants (CNVs) are associated with many neurocognitive disorders; however, these events are typically large, and the underlying causative genes are unclear. We created an expanded CNV morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. We resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls.

Skin and self-injury: a possible link between peripheral innervation and immune function?

The aim of this preliminary case study series was to investigate epidermal innervation in pediatric patients with significant neurological impairment and self-injurious behavior. We enrolled four pediatric patients with self-injury (two males, two females; mean age 12y, range 9-14y) and used archival specimens from healthy, age-matched children with typical development for comparison purposes. Epidermal nerve fiber density, peptide content, and mast cell degranulation patterns from non-damaged skin were tested between the patients and the comparison group.

Parent-reported pain in Rett syndrome.

Objectives: Clinical reports suggest that patients with Rett syndrome (RTT) live with significant chronic health issues as well as severe motor and communication impairments. Consequently, patients with RTT may be at risk for living with pain but not having it recognized. The purpose of this preliminary study was to document parent reported estimates of pain frequency, pain communication, and pain source.

The duplication 17p13.3 phenotype: analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes.

Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities.

Investigation of NRXN1 deletions: clinical and molecular characterization.

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray-based comparative genomic hybridization.

Seizures and pain uncertainty associated with parenting stress and Rett syndrome.

Data were collected parenting stress, adaptive behavior, pain, and health issues from the caregivers of 35 girls and women with Rett syndrome (mean age = 20.3). A majority (60%) of parents reported stress in the clinical range on at least 1 subscale of the Parenting Stress Index-Short Form.

Rasch analysis of items from two self-report measures of motor function: determination of item difficulty and relationships with children's ability levels.

Aim: The aim of this article was to determine item measurement properties of a set of items selected from the Gillette Functional Assessment Questionnaire (FAQ) and the Pediatric Outcome Data Collection Instrument (PODCI) using Rasch analysis, and to explore relationships between the FAQ/PODCI combined set of items, FAQ walking scale level, Gross Motor Function Classification System (GMFCS) levels, and the Gait Deviation Index on a common measurement scale.

Method: Rasch analysis was performed on data from a retrospective chart review of parent-reported FAQ and PODCI data from 485 individuals (273 males; 212 females; mean age 9 y 10 mo, SD 3 y 10 mo) who underwent first-time three-dimensional gait analysis. Of the 485 individuals, 289 had a diagnosis of cerebral palsy (104 GMFCS level I, 97 GMFCS level II, 69 GMFCS level III, and 19 GMFCS level IV).

Microdeletion of Xq28 involving the AFF2 (FMR2) gene in two unrelated males with developmental delay.

Fragile X E (FRAXE) is an X-linked form of intellectual disability characterized by mild to moderate cognitive impairment, speech delay, hyperactivity, and autistic behavior. The folate-sensitive fragile site FRAXE is located in Xq28 approximately 600 kb distal to the fragile X syndrome fragile site (FRAXA) and harbors an unstable GCC (CCG) triplet repeat adjacent to a CpG island in the 5' untranslated region of the AFF2 (FMR2) gene. The disorder results from amplification and methylation of the GCC repeat and resultant silencing of AFF2.

Developmental and behavior problems predict parenting stress in young children with global delay.

To identify parent-reported symptoms that predict parenting stress in preschoolers with global developmental delay, 201 parents/guardians of 142 boys and 59 girls with global delay, mean age 39.1 months (range, 18 to 63 months) were studied retrospectively. Parents completed the following: (a) a semistructured interview; (b) the Child Development Inventory, (c) Child Behavior Checklist 1½-5, and the (d) Parenting Stress Index-Short Form.

High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44.

Microdeletions of 1q43q44 result in a recognizable clinical disorder characterized by moderate to severe intellectual disability (ID) with limited or no expressive speech, characteristic facial features, hand and foot anomalies, microcephaly (MIC), abnormalities (agenesis/hypogenesis) of the corpus callosum (ACC), and seizures (SZR). Critical regions have been proposed for some of the more prominent features of this disorder such as MIC and ACC, yet conflicting data have prevented precise determination of the causative genes. In this study, the largest of pure interstitial and terminal deletions of 1q43q44 to date, we characterized 22 individuals by high-resolution oligonucleotide microarray-based comparative genomic hybridization.

Deletions and duplications of developmental pathway genes in 5q31 contribute to abnormal phenotypes.

Although copy number changes of 5q31 have been rarely reported, deletions have been associated with some common characteristics, such as short stature, failure to thrive, developmental delay (DD)/intellectual disability (ID), club feet, dislocated hips, and dysmorphic features. We report on three individuals with deletions and two individuals with duplications at 5q31, ranging from 3.6 Mb to 8.

French norms and validation of the Child Development Inventory (CDI): Inventaire du Developpement de l'Enfant (IDE).

The aim of this study was to determine the French norms and examine the validity of a parent-report inventory: the Child Development Inventory (CDI), called "Inventaire du Développement de l'Enfant (IDE)" in French. This assesses the general level of a child's development in 8 developmental domains. The norms were determined for a community sample of 1287 children, aged 15 to 72 months.

22q13.32 deletion and duplication and inversion in the same family: a rare occurrence.

Chromosome 22q13.3 deletion syndrome is a well-recognized cause of global developmental delay, while duplication of the same chromosome is a rare occurrence. The presence of both abnormalities in the same family has never been reported, to our knowledge.

Self-injury among a community cohort of young children at risk for intellectual and developmental disabilities.

Objective: To identify risk factors for self-injurious behavior in young children with developmental delay and to determine whether that group is also more likely to exhibit other challenging behaviors.

Study Design: A retrospective chart review of 196 children < 6 years of age referred for comprehensive neurodevelopmental evaluations. We analyzed child developmental level, receptive and expressive communication level, mobility, visual and auditory impairment, and co-morbid diagnoses of cerebral palsy, seizure disorders, and autism.

Attention problems and parent-rated behavior and stress in young children at risk for developmental delay.

The aim of this article is to characterize the neurobehavior of young children at risk for developmental delay and attention problems. Two hundred and eighty-one children, ages 18 to 70 months, were evaluated. All parents/guardians completed the Child Development Inventory, Child Behavior Checklist for Ages 1½ to 5, Inventory for Client and Agency Planning, and Parenting Stress Index-Short Form.

The principle of double effect, genetic testing, and global developmental delay.

Well-intended efforts to diagnose a child's developmental delay may have unintended negative consequences for a child and his family. Consequently, clinicians may feel caught in a moral dilemma: between doing the good they seek and avoiding the harm they foresee. The dilemma is that when investigating global developmental delay it is not possible to avoid all the anticipated negative outcomes of genetic testing and concurrently fulfill our obligations to do the good from which these harmful effects result.

Parents' reports predict abnormal investigations in global developmental delay.

Aims: To identify symptoms reported by parents that predict abnormal laboratory investigations in preschoolers with global developmental delay (GDD).

Methods: A cross-sectional descriptive study of 81 boys and 38 girls, with a mean age of 43.5 months (SD = 13.

Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication.

Background: Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported.

The effects of methylphenidate on the classroom behavior of elementary school-age children with cerebral palsy: a preliminary observational analysis.

High- and low-dose methylphenidate administration was evaluated prospectively for 3 elementary school-age children with cerebral palsy, cognitive impairments, and attention-deficit hyperactivity disorder (ADHD) symptoms using single-case, randomized, double-blind, placebo-controlled designs. An observational time sampling protocol was used to directly measure and quantify classroom behavior. Summary level analysis showed that (1) low-dose (0.

Language proficiency, development, and behavioral difficulties in toddlers.

The aim of this cross-sectional descriptive study was to explore the relation of language proficiency, behavioral difficulties, and development in infants and toddlers. Surveyed were 118 parents/caregivers of preschool children (76 boys, 42 girls). The children were a mean age of 27 months (range, 18-35 months), and 32 (27.

Parent evaluation of spasticity treatment in cerebral palsy using botulinum toxin type A.

Objective: To assess parent ratings of treatment acceptability associated with botulinum toxin type A (BTX-A) injection for spasticity in children with cerebral palsy (CP).

Design: A single-point survey design across a sequentially recruited cohort, using a standardized evaluation measure.

Setting: Regional specialty health care center medical clinic and pain research program.