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Background Pierre Robin sequence (PRS) is a heterogeneous condition involving retro(micro)gnathia, glossoptosis and upper airway obstruction, very often with posterior cleft palate. Patients with PRS, either isolated or associated with Stickler syndrome have good intellectual prognosis. Nevertheless, the quality of life in adolescence and the phonatory and morphological outcomes are rarely analysed. We assessed the phonatory and morphological outcomes of 72 cognitively unimpaired adolescents with PRS, studied their oral (COHIP-SF19), vocal (VHI-9i) and generic quality of life (QoL; KIDSCREEN-52), and searched for determinants of these outcomes. Results Two-thirds of our adolescents retained low or moderate phonation difficulties, but risk factors were not identified. For 14%, morphological results were considered disharmonious, with no link to neonatal retrognathia severity. Only one vs two-stage surgery seemed to affect final aesthetic results. The oral QoL of these adolescents was comparable to that of control patients and was significantly better than that of children with other craniofacial malformations (COHIP-SF19 = 17.5, 15.4 and 25.7, respectively). The oral QoL of the adolescents with non-isolated PRS was significantly worse (COHIP-SF19 = 24.2) than that of control patients and close to that of children with other craniofacial malformations. The vocal QoL of the adolescents (mean [SD] VHI-9i = 7.5 [5.4]) was better than that of patients with other voice pathologies and better when phonation was good. The generic QoL of the adolescents was satisfactory but slightly lower than that of controls, especially in dimensions concerning physical well-being, relationships and autonomy. QoL results were lower for adolescents with non-isolated than isolated PRS. Only non-isolated PRS and low oral QoL affected generic QoL. Conclusion Morphological or phonatory impairments remain non-rare in adolescents with PRS but do not seem to be directly responsible for altered QoL. These adolescents, especially those with non-isolated PRS, show self-confidence and social-relation fragility. We must focus on long-term functional and psychological results for PRS patients and improve therapy protocols and follow-up, notably those affecting the oral aspects of the disease.

ARID1B mutations in Coffin-Siris syndrome are a cause of intellectual disability (0.5-1%), with various degrees of autism and agenesis of the corpus callosum (10%). Little is known regarding the cognitive and motor consequences of ARID1B mutations in humans and no link has been made between corpus callosum anomalies and visuospatial and neuromotor dysfunctions. We have investigated the visuospatial and neuromotor phenotype in eight patients with ARID1B mutations. A paramedian sagittal section of the brain MRI was selected, and corpus callosum was measured in anteroposterior length, genu and trunk width. Spearman's rank order coefficients were used to explore correlations between visuospatial and social cognitive variables and dimensions of the corpus callosum. A significant correlation between genu width size and visual cognition was observed. Retrocerebellar cysts were associated with corpus callosum anomalies. Here, we show that corpus callosum anomalies caused in ARID1B mutations may be predictive of the visuospatial and motor phenotype in Coffin-Siris syndrome.

Neonatal Diabetes (ND) mellitus is a rare genetic disease (1 in 90,000 live births). It is defined by the presence of severe hyperglycaemia associated with insufficient or no circulating insulin, occurring mainly before 6 months of age and rarely between 6 months and 1 year. Such hyperglycaemia requires either transient treatment with insulin in about half of cases, or permanent insulin treatment. The disease is explained by two major groups of mechanism: malformation of the pancreas with altered insulin-secreting cells development/survival or abnormal function of the existing pancreatic β cell. The most frequent genetic causes of neonatal diabetes mellitus with abnormal β cell function are abnormalities of the 6q24 locus and mutations of the ABCC8 or KCNJ11 genes coding for the potassium channel in the pancreatic β cell. Other genes are associated with pancreas malformation or insufficient β cells development or destruction of β cells. Clinically, compared to patients with an ABCC8 or KCNJ11 mutation, patients with a 6q24 abnormality have lower birth weight and height, are younger at diagnosis and remission, and have a higher malformation frequency. Patients with an ABCC8 or KCNJ11 mutation have neurological and neuropsychological disorders in all those tested carefully. Up to 86% of patients who go into remission have recurrent diabetes when they reach puberty, with no difference due to the genetic origin. All these results reinforce the importance of prolonged follow-up by a multidisciplinary pediatric team, and later doctors specializing in adult medicine. 90% of the patients with an ABCC8 or KCNJ11 mutation as well as those with 6q24 anomalies are amenable to a successful switch from insulin injection to oral sulfonylureas.

Summary Objectives Children with developmental coordination disorder (DCD) are particularly affected by handwriting disorders, which remain poorly understood and are not clearly defined. The aim of our study is to provide a better understanding of handwriting disorders, and specifically of dysgraphia in children with DCD. Methods Sixty-five children with DCD (5–15 years), enrolled according to DSM-5, were assessed with handwriting testing and standardized assessments of neuropsychological, neurovisual, MRI and neuropsychomotor functions, with special attention paid to muscular tone examination. Results While handwriting disorders were strongly represented in our sample of children with DCD (89%), dysgraphia appeared uncommon (17%) and was closely related to several specific dysfunctions of laterality establishment; mild pyramidal tract dysfunction with distal phasic stretch reflex (PSR) in lower limbs; digital praxis slowness (both P Discussion In our sample, dysgraphia was closely related to minor neurological dysfunction (MND) suggesting a disturbance of motor control at the level of the corticospinal motor pathway. This highlights the uncommon character of dysgraphia in children with DCD for which diagnosis should be made through a particular attention to evaluation of MND with muscular tone examination. This consideration, both in the research setting and in clinical practice, appears necessary to avoid inaccurate clinical diagnosis and to optimize appropriate therapeutic management.

Chromosome 6 abnormalities such as paternal uniparental isodisomy, paternal 6q24 duplication, and maternal DMR (differentially methylated region) hypomethylation are a common cause of transient neonatal diabetes mellitus (TNDM). Oral sulfonylurea (SU) is used off-label to treat permanent neonatal diabetes mellitus owing to potassium channel mutation but has not been evaluated in TNDM. Our objective was to evaluate the efficacy and safety of SU therapy in chromosome 6-related TNDM. Description of 3 case reports and literature review was the subject of the study. SU therapy was successful in 2 patients (initiated during neonatal life in 1 patient and during relapse in the other) but failed in the other despite the use of high dosage. The literature review identified 11 cases of patients with chromosome 6-related TNDM treated with SU, including 4 treated before remission and 7 after the relapse. SU therapy was consistently effective, although 4 patients treated after the relapse required multiple oral medications. None of the patients needed associated insulin therapy. No side effects of SU or complications of diabetes were reported. SU seems effective and safe in chromosome 6-related TNDM treatment when used to treat the initial episode of diabetes or the relapse. It improves patients' and families' quality of life. SU is available only as oral tablets. A pediatric dosage form would facilitate the treatment of neonates and infants.

IntroductionHandwriting disorder is commonly observed in Developmental Coordination Disorder (DCD) (87-88%) and is often noted in children with high Intellectual Quotient (HIQ).Two mainly pure DCD subtypes: ideomotor-DCD (IM), visuospatial/or visuoconstructional-DCD (VSC) and a mixed subtype (MX) were identified in the literature but nothing is known regarding IQ and dysgraphia.ObjectivesTo refine the specific clinical features of dysgraphia related to DCD subtypes regarding IQ levels.Methods Neurovisual, neuropsychological, neuropsychomotor functions, and handwriting performances of 38 children (6-to-12 years-old: mean 9y, SD 2.7) diagnosed with DCD (DSM-5 criteria) were collected. Two matched groups were analyzed according to their IQ: 19 (TC) typical children (IQ=90-110) and 19 HIQ children (IQ> 120).Results IQ scores were not significantly associated with dysgraphia. There isa significant difference between TC vs HIQ with a lower rate of IM-DCD respectively 11% vs 5% (p=.035) and 68% vs 37% for VSC-DCD (p=.03) but 21% vs 58% in MX-DCD (p=.41). Dysgraphia was significantly more present in TC group with MX-DCD and in HIQ with VSC-DCD. A negative correlation between Kho’s’ cubes test failure (p=.006), visual-spatial memory (p=.05) and VSC-DCD was noted in HIQ group. The deficit of visual spatial memory was significantly related to dysgraphia in HIQ children (p=.01) associated to visual gnosis impairment (p=.03).ConclusionsDysgraphia was significantly found with VSC-DCD subgroup in FIQ>120 with specific features of visual perception disorders suggesting more involvement of the right cortex. These results suggest that VSC-DCD in HIQ could be a neurovisual impairment rather than a pure VSC-DCD.

Objective: Handwriting difficulties are commonly observed in children with high intellectual quotient (HIQ) and generally associated to developmental coordination disorder (DCD) but remain poorly understood. The aim of our study is to refine the specific clinical features of handwriting disorders in children with DCD regarding their IQ level. Method: Neurovisual, neuroimaging, neuropsychological, neuropsychomotor functions, and handwriting performances of 38 children (6-to-12 years-old: mean 9y, SD 2.7), diagnosed with DCD (DSM-5 criteria), were analyzed. Among them, two matched groups were studied according to the Full IQ (FIQ) level: 19 typical-children (FIQ=90-110) and 19 HIQ children (FIQ> 120). Results: Handwriting difficulties were present in both groups without statistical difference. Dysgraphia was significantly related to pyramidal-tract-dysfunction (p=0.01) and electroretinogram abnormalities (p=0.03) in both groups. In HIQ children, a specific marker was identified: visual gnosis impairment associated to deficit of visual-spatial memory. Conclusions: Dysgraphia is a severe diagnosis involving the central nervous system, affecting the motor and neurovisual pathways and it rather appears as a comorbidity to DCD. Neurological-soft-signs and electroretinogram abnormalities can be considered as interesting clinical markers of dysgraphia in children with DCD. Children having FIQ>120 display visual gnosis disorder as a specific clinical marker of dysgraphia.

Background Behavioral problems are an important issue for people with CHARGE syndrome. The similarity of their behavioral traits with those of people with autism raises questions. In a large national cross-sectional study, we used specific standardized tools for diagnosing autism (Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders, 5th edition, DSM-5) and evaluating behavioral disorders (Developmental Behavior Checklist-Parents, DBC-P) to investigate a series of individuals with CHARGE syndrome, defined by Verloes’s criteria. We evaluated their adaptive functioning level and sensory particularities and extracted several data items from medical files to assess as potential risk factors for autism and/or behavioral disorders. Results We investigated 64 individuals with CHARGE syndrome (35 females; mean age 10.7 years, SD 7.1 years). Among 46 participants with complete results for the Autism Diagnostic Interview-Revised (ADI-R), 13 (28%) had a diagnosis of autism according to the ADI-R, and 25 (54%) had a diagnosis of autism spectrum disorder (ASD) according to the DSM-5 criteria. The frequency of autistic traits in the entire group was a continuum. We did not identify any risk factor for ASD but found a negative correlation between the ADI-R score and adaptive functioning level. Among 48 participants with data for the DBC-P, 26 (55%) had behavioral disorders, which were more frequent in patients with radiological brain anomalies, impaired adaptive functioning, later independent walking, and more sensory particularities. Conclusions ASD should be considered to be an independent risk requiring early screening and management in children born with CHARGE syndrome.

Posterior fossa arachnoid cysts (PFAC) are mostly considered as benign lesions of the cerebellum. Although many studies have shown the major role of the cerebellum in modulating movement, language, cognition, and social interaction, there are few studies on the cognitive impact and surgical decompression of PFAC.We present the cases of two brothers successively diagnosed with PFAC and neuropsychological delay. After multidisciplinary discussion with the boys' parents, it was decided to drain these lesions. Clinical signs, cerebral images, and neuropsychological status were assessed on admission and then 1 and 3 years after surgery.At presentation, both children had mild cerebellar signs, associated with cognitive and visual-motor impairments and academic regression. CT scans revealed retrovermian cysts, which were shunted. Post-operatively, both brothers demonstrated improved visual-motor skills and behavior. At follow-up, we observed disappearance of dysarthria and academic delay and significant improvement in cognition especially at the intelligence scale and in language. Fine motor skills had improved but remained slower than the average and writing skills appeared limited.Except for PFAC which impair cerebrospinal fluid circulation or which are responsible for a significant mass effect, most PFAC are usually considered as "asymptomatic" and do not require surgical treatment. The two cases reported herein suggest that these lesions might be responsible for some associated but potentially reversible neuropsychological impairment. In the future, clinical assessment should include neuropsychological evaluation to help inform decision for surgical decompression in these children with PFAC.

Motor symptomatology in autism is currently poorly understood, and still not included in the autism spectrum disorder (ASD) diagnostic criteria, although some studies suggest the presence of motor disturbances in this syndrome. We provide here a literature review on early motor symptoms in autism, focusing on studies on psychomotor issues (tone, postural control, manual dexterity, handedness, praxis). The approach adopted in research to study altered motor behaviors is generally global and there is no detailed semiology of the motor or neuromotor disorders observed in people with ASD. This global approach does not enable understanding of the neuro-developmental mechanisms involved in ASD. Identification of clinical neuro-psychomotor profiles in reference to a standard would help to better understand the origin and the nature of the disorders encountered in ASD, and would thus give new directions for treatment.

Summary Objective Motor disorders are known in autism spectrum disorder (ASD), but muscle tone assessments are rarely performed. Muscle tone underpins movement. We investigated muscle tone in 34 ASD children using a standardized neuro-developmental battery, which uses the French norms for muscular tone in children. Methods Dangling and extensibility were used to examine passive muscle tone in the upper and lower limbs and the body axis. A comparison between muscles of the right and left sides enabled the determination of tonic laterality. Results We found a disharmonious tonic typology, with a tonic component for the muscles of the trunk and the proximal muscles of the lower limbs and a laxity component for the ankles and the proximal and distal muscles of the upper limbs (wrists and shoulders). No establishment of tonic laterality was found in the upper limbs in 61% of ASD children (P Conclusion The disturbed tonic organization influenced by subcortical structures, such as the cerebellum, may partially explain the motor disorders, and indefinite tonic laterality may also be linked to low hemispheric brain dominance described in autism. This preliminary examination is necessary before any gross motor assessments to understand the nature of movement disorders, explore typologies and highlight possible soft neuro-motor signs.

A detailed assessment of laterality in children with Autism Spectrum Disorder (ASD) was realized, including handedness and other measures (muscle tone, manual performance, dominant eye), using a standardized battery for the developmental assessment of neuro-psychomotor functions. The results of the laterality tests relating to cerebral hemisphere organization (spontaneous gestural laterality and tonic laterality) were different in ASD children, and indicate that the cerebral organization could be disrupted. These assessments, added to the observations of usual laterality most often reported in the literature, provide better understanding of the developmental organization from the pathophysiological point of view in children with ASD.

In the literature, descriptions of children with motor coordination difficulties and clumsy movements have been discussed since the early 1900s. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), it is a marked impairment in the development of fine or global motor coordination, affecting 6% of school-age children. All these children are characterized for developmental coordination disorder (DCD) in motor learning and new motor skill acquisition, in contrast to adult apraxia which is a disorder in the execution of already learned movements. No consensus has been established about etiology of DCD. Intragroup approach through factor and cluster analysis highlights that motor impairment in DCD children varies both in severity and nature. Indeed, most studies have used screening measures of performance on some developmental milestones derived from global motor tests. A few studies have investigated different functions together with standardized assessments, such as neuromuscular tone and soft signs, qualitative and quantitative measures related to gross and fine motor coordination and the specific difficulties -academic, language, gnosic, visual motor/visual-perceptual, and attentional/executive- n order to allow a better identification of DCD subtypes with diagnostic criteria and to provide an understanding of the mechanisms and of the cerebral involvement.

CHARGE Syndrome (CS) is a rare genetic disease involving somatic malformations and multisensory impairments. The association of CS with autism spectrum disorders remains a controversial issue because it remains challenging to clinically assess symptoms of autism in young children with potential severe somatic conditions, deaf blindness and mental delay and the behavior troubles often encountered in individuals with CS can be considered the consequence of their multisensory deficits and medical history. We report the complex developmental trajectory of a 25-year-old girl with typical CS, with emotional disorders and problematic behaviors that led to a diagnosis of autism. Addressed by a multidimensional and integrative perspective, this situation reveals the coexistence of factors and impairments not causally connected but whose constant interactions during her development must be evaluated. In this way, clinicians can achieve a functional diagnosis enabling the elaboration of a tailored therapeutic proposal.

Background: An increasing number of clinicians point to similar clinical features between some children with High Intellectual Potential (HIP or “Giftedness” = Total IQ > 2 SD), and children with Autism Spectrum Disorder (ASD) without intellectual or language delay, formerly diagnosed with Asperger Syndrome. Some of these common features are social interaction impairments, special interests, and in some cases high-verbal abilities. The aim of this article is to determine whether theses similarities exist at more fundamental levels, other than clinical, and to explore the literature in order to provide empirical support for an overlap between ASD and HIP. Method: First, comparative studies between ASD and HIP children were sought. Because of a lack of data, the respective characteristics of ASD and HIP subjects were explored by a cross-sectional review of different areas of research. Emphasis was placed on psychometric and cognitive evaluations, experimental and developmental assessments, and neurobiological research, following a “bottom-up” procedure. Results: This review highlights the existence of similarities in the neurocognitive, developmental and neurobiological domains between these profiles, which require further study. In addition, the conclusions of several studies show that there are differences between HIP children with a homogeneous Intellectual Quotient profile and children with a heterogeneous Intellectual Quotient profile. Conclusion: HIP seems to cover different developmental profiles, one of which might share features with ASD. A new line of investigation providing a possible starting-point for future research is proposed. Its implications, interesting from both clinical and research perspectives, are discussed.

IntroductionAn overlap between autism spectrum disorder (ASD), in particular Asperger Syndrome (AS), and high intellectual potential (HIP–Total IQ > 2 SD) is often discussed.ObjectivesExplore differences between homogeneous and heterogeneous Wisc-profiles among HIP children, and between HIP and ASD children, on cognitive and clinical assessments.MethodsForty-nine participants (mean age 11.2 years) were divided in 4 groups: High Functioning Autism (HFA), AS, Homogenous HIP and Heterogeneous HIP. Data of WISC-IV and questionnaires – Autism Quotient (AQ), Empathy Quotient (EQ), Systemizing Quotient (SQ), Children's Communication Checklist (CCC) – were compared.(Preliminary) ResultsOn the WISC-IV, the Z scores curves follow similar trajectories but highlight quantitative differences between AS and heterogeneous HIP: verbal comprehension is the highest index (+1,6 SD in AS; +3,1 SD in heterogeneous HIP) followed by perceptual reasoning, working memory, and processing speed indexes (–1,2 SD in AS; +0,5 SD in heterogeneous HIP), respectively. The questionnaires show that scores of Homogenous HIP children are all in the average. Heterogeneous HIP children score 2,1 SD above average on the AQ (+1,6 SD on “Social Skills” and +1,3 SD on “Local Detail” subscales), whereas ASD children score 4 SD above average on the AQ. In addition, heterogeneous HIP children show pragmatic difficulties (–2,4 SD on the CCC, with a peak on “Area of Interest” subscale), also present in ASD children (–4 SD).ConclusionsAS and heterogeneous HIP children show similar cognitive profiles on the WISC-IV. Furthermore, heterogeneous HIP children exhibit high scores on the AQ and have pragmatic difficulties.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Data on growth status at birth in a French sample of gifted children identified at school age were analysed in a retrospective survey. Birth weight, gestational age, head circumference, stature, gender, parental socio-economic status, information on the pregnancy, and motor development were recorded. On the basis of standard growth curves, the sample was characterised according to the 10th, 50th, 75th and 90th percentiles. Three groups of gestational age were determined: preterm births (18.6%), full term births (63.2%) and post-term births (18.1%) with a high frequency of hypertrophy in preterm births (≥ 90th). Intellectual quotient (IQ) did not differ among the groups, showing a notable advance in motor development. This research shows that, among children later identified as gifted, compared to those born full term, preterm infants showed a significant relationship between homogeneity in anthropometric variables and future motor and intellectual development when these children were exposed to a favourable perinatal environment (few pregnancy complications) and a favourable postnatal parental socio-economic status.

OBJECTIVE. The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No. 606232) is a neurodevelopmental disorder that includes hypotonia, severely impaired development of speech and language, autistic-like behavior, and minor dysmorphic features. Although the number of reported cases is increasing, the 22q13.3 deletion remains underdiagnosed because of failure in recognizing the clinical phenotype and detecting the 22qter deletion by routine chromosome analyses. Our goal is to contribute to the description of the neurobehavioral phenotype and brain abnormalities of this microdeletional syndrome. METHODS. We assessed neuromotor, sensory, language, communication, and social development and performed cerebral MRI and study of regional cerebral blood flow measured by positron emission tomography in 8 children carrying the 22q13.3 deletion. RESULTS. Despite variability in expression and severity, the children shared a common developmental profile characterized by hypotonia, sleep disorders, and poor response to their environment in early infancy; expressive language deficit contrasting with emergence of social reciprocity from ages ∼3 to 5 years; sensory processing dysfunction; and neuromotor disorders. Brain MRI findings were normal or showed a thin or morphologically atypical corpus callosum. Positron emission tomography study detected a localized dysfunction of the left temporal polar lobe and amygdala hypoperfusion. CONCLUSIONS. The developmental course of the 22q13.3 deletion syndrome belongs to pervasive developmental disorders but is distinct from autism. An improved description of the natural history of this syndrome should help in recognizing this largely underdiagnosed condition.

We investigated the recognition of pairs of faces (same or different facial identities and expressions) in two groups of 14 children aged 6-10 years, with either an expressive language disorder (ELD), or a mixed language disorder (MLD), and two groups of 14 matched healthy controls. When looking at their global performances, children with either expressive (ELD) or MLD have few differences from controls in either face or emotional recognition. At contrary, we found that children with MLD, but not those with ELD, take identical faces to be different if their expressions change. Since children with mixed language disorders are socially more impaired than children with ELD, we think that these features may partly underpin the social difficulties of these children.

OBJECTIVE Neonatal diabetes secondary to mutations in potassium-channel subunits is a rare disease but constitutes a paradigm for personalized genetics-based medicine, as replacing the historical treatment with insulin injections with oral sulfonylurea (SU) therapy has been proven beneficial. SU receptors are widely expressed in the brain, and we therefore evaluated potential effects of SU on neurodevelopmental parameters, which are known to be unresponsive to insulin. RESEARCH DESIGN AND METHODS We conducted a prospective single-center study. Nineteen patients (15 boys aged 0.1–18.5 years) were switched from insulin to SU therapy. MRI was performed at baseline. Before and 6 or 12 months after the switch, patients underwent quantitative neurological and developmental assessments and electrophysiological nerve and muscle testing. RESULTS At baseline, hypotonia, deficiencies in gesture conception or realization, and attention disorders were common. SU improved HbA1c levels (median change −1.55% [range −3.8 to 0.1]; P < 0.0001), intelligence scores, hypotonia (in 12 of 15 patients), visual attention deficits (in 10 of 13 patients), gross and fine motor skills (in all patients younger than 4 years old), and gesture conception and realization (in 5 of 8 older patients). Electrophysiological muscle and nerve tests were normal. Cerebral MRI at baseline showed lesions in 12 patients, suggesting that the impairments were central in origin. CONCLUSIONS SU therapy in neonatal diabetes secondary to mutations in potassium-channel subunits produces measurable improvements in neuropsychomotor impairments, which are greater in younger patients. An early genetic diagnosis should always be made, allowing for a rapid switch to SU.

Introduction Although the terminology of Asperger’s Syndrome has been subsumed within high functioning autism in the last edition of the DSM, the absence of a clear consensus concerning the relevance of the distinction between HFA and AS persists among researchers and clinicians. Besides, the frequent convergence of clinical signs between AS and intellectual high potential encourages to investigate the existence of parallels and their nature. The current situation contributes to maintain confusion at the diagnostically level and by extension to hamper the care system. Objectives Explore and better define three atypical neurocognitive profiles: HFA, AS and intellectual high potential, in order to refine the criteria for a more accurate identification. Methods Data will be collected from 5 groups of children: 'typical HFA”, 'typical AS”, 'typical gifted children”, 'atypical” (ambiguous diagnosis) and control. These groups will be compared to each other at multiple level: cognition, language, social cognition, psychomotor assessment. Evaluations will be completed by questionnaires and by a clinical interview process (anamnestic data). Results expected 'Typical” gifted children, even when they exhibit social issues, don’t have constitutional deficit in the area of social cognition and perform normally or above average in such tasks. Children with heterogeneous psychometric profiles show neuropsychological and/or psychopathological disorders. AS group performs better in language dimension and verbal comprehension (vocabulary, verbal abstraction) than HFA group. In addition, AS children might present motor coordination difficulties and undetermined lateralization more frequently than HFA children. Conclusions Despite these differences, these children exhibit atypical developmental trajectories characterized by heterochrony.

IntroductionAlthough more than 85% of children with DCD are affected by handwriting disorders, their characteristics and underlying mechanisms remain poorly known.ObjectivesWe aim to better identify the nature of handwriting disorders in subtyping DCD children.MethodsSchool children aged between 5 to 15 years and exhibited a DCD (according to DSM-5) are eligible for inclusion. They were classified in three subtypes of DCD: ideomotor (IM), visual-spatial and/or constructional (VSC), and mixed (MX). They were assessed with a standardized handwriting evaluation including quality and speed and a clinical observation of motor gestual developmental and temporal-spatial organization of handwriting highlighting six qualitative criteria: irregular handwriting (criterion 1), immaturity of handwriting gesture (criterion 2), excessive pressure of the pen on the paper (criterion 3), neuro-vegetative responses (criterion 4), trembling (criterion 5), slow handwriting velocity (criterion 6). Two groups are established: children with poor handwriting (PH) and children with dysgraphia (DysG).ResultsWhile 89% of children have handwriting disorders, only 20% exhibit dysgraphia. IM DCD is characterized by an immaturity of handwriting gesture and is associated with PH. Dysgraphia appears only in VSC and MX DCD which are characterized by the association of criteria 1, 2, 3, and 4. This association appears to more than 80% in DysG. Slow handwriting velocity is constant between PH and DysG.ConclusionImmaturity of handwriting gesture is a possible underlying mechanism of poor handwriting. Dysgraphia is associated with specific impairments in spatial organization of letters and in motor control of handwriting gesture.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Neonatal diabetes mellitus is a rare genetic form of pancreatic β-cell dysfunction. We compared phenotypic features and clinical outcomes according to genetic subtypes in a cohort of patients diagnosed with neonatal diabetes mellitus before age 1 year, without β-cell autoimmunity and with normal pancreas morphology.We prospectively investigated patients from 20 countries referred to the French Neonatal Diabetes Mellitus Study Group from 1995 to 2010. Patients with hyperglycaemia requiring treatment with insulin before age 1 year were eligible, provided that they had normal pancreatic morphology as assessed by ultrasonography and negative tests for β-cell autoimmunity. We assessed changes in the 6q24 locus, KATP-channel subunit genes (ABCC8 and KCNJ11), and preproinsulin gene (INS) and investigated associations between genotype and phenotype, with special attention to extra-pancreatic abnormalities.We tested 174 index patients, of whom 47 (27%) had no detectable genetic defect. Of the remaining 127 index patients, 40 (31%) had 6q24 abnormalities, 43 (34%) had mutations in KCNJ11, 31 (24%) had mutations in ABCC8, and 13 (10%) had mutations in INS. We reported developmental delay with or without epilepsy in 13 index patients (18% of participants with mutations in genes encoding KATP channel subunits). In-depth neuropsychomotor investigations were done at median age 7 years (IQR 1-15) in 27 index patients with mutations in KATP channel subunit genes who did not have developmental delay or epilepsy. Developmental coordination disorder (particularly visual-spatial dyspraxia) or attention deficits were recorded in all index patients who had this testing. Compared with index patients who had mutations in KATP channel subunit genes, those with 6q24 abnormalities had specific features: developmental defects involving the heart, kidneys, or urinary tract (8/36 [22%] vs 2/71 [3%]; p=0·002), intrauterine growth restriction (34/37 [92%] vs 34/70 [48%]; p0·0001), and early diagnosis (median age 5·0 days, IQR 1·0-14·5 vs 45·5 days, IQR 27·2-95·0; p0·0001). Remission of neonatal diabetes mellitus occurred in 89 (51%) index patients at a median age of 17 weeks (IQR 9·5-39·0; median follow-up 4·7 years, IQR 1·5-12·8). Recurrence was common, with no difference between the groups who had 6q24 abnormalities versus mutations in KATP channel subunit genes (82% vs 86%; p=0·36).Neonatal diabetes mellitus is often associated with neuropsychological dysfunction and developmental defects that are specific to the underlying genetic abnormality. A multidisciplinary assessment is therefore essential when patients are diagnosed. Features of neuropsychological dysfunction and developmental defects should be tested for in adults with a history of neonatal diabetes mellitus.Agence Nationale de la Recherche-Maladies Rares Research Program Grant, the Transnational European Research Grant on Rare Diseases, the Société Francophone du Diabète-Association Française du Diabète, the Association Française du Diabète, Aide aux Jeunes Diabétiques, a CIFRE grant from the French Government, HRA-Pharma, the French Ministry of Education and Research, and the Société Française de Pédiatrie.

Background Parents with past and current eating disorders (ED) have been shown to report troubles nourishing their infants. This could increase the risk of infant feeding problems linked to maternal anxiety and depression. It is not clear how mothers’ eating difficulties before pregnancy and at the time of birth can affect infant’s feeding. We aimed to specify the impact of eating disorders on mothers’ adaptation and sensitivity to their offspring during feeding, by comparing a population of mothers with eating disorders and controls. Methods Twenty-eight women agreed to participate in interviews and filmed mother-baby interactions. Pregnant women consulting at an obstetric unit for care follow-up were screened and tested for symptoms of eating disorders with the EDE-Q Questionnaire (Eating Disorders Examination Questionnaire) and the EDE Interview (Eating Disorders Examination Interview). Infant functional troubles and mothers’ sensitivity were investigated through the Symptom Check List. Reciprocal adaptation during feeding with their new-borns was filmed and analysed with the Chatoor Infant Feeding Scale. Before pregnancy, two women suffered from anorexia, three suffered from bulimia, three had binge eating symptoms and two were diagnosed with EDNOS (Eating Disorders Not Otherwise Specified). Results Mothers suffering from ED tended to show more difficult interactive patterns in terms of dyadic reciprocity when feeding their babies compared with mothers with no symptoms of eating disorders. In the interviews, other than the behavioural data gathered, ED mothers expressed feeling more dissatisfaction and uneasiness during feeding. Conclusions Pregnancy seems to be an useful period for interviewing women on eating disorders, allowing for the design and implementation of prevention programmes based on mothers’ narratives and infant/mother observations and treatment.

Anhidrotic/hypohidrotic ectodermal dysplasia (HED) is the most common of the ectodermal dysplasias characterized by a triad of absent or reduced sweat, hypodontia and misshapen teeth, and missing or sparse hair. As the central nervous system is primarily ectodermal in origin, it has long been a concern that HED may be associated with developmental delay and/or intellectual disabilities. While published reviews report abnormalities in mental or motor development in 15-25% of HED-affected patients, there is no report in the literature including a systematic assessment of intellectual abilities in a cohort of patients with this rare disorder. During yearly health care updates, many of our clinic families report attention difficulties in young HED patients without evidence of a significant impact on school performance. In an exploratory study to identify and quantify intellectual abnormalities that may be associated with HED, we performed a psychological examination of 23 HED patients by means of the Wechsler Intelligence Scales, WPPSI-III, and WISC-IV. The interpretation of the tests shows no significant impairment in the achievements of the sample group compared with normative values (full scale scores, and index scale scores of the WISC-IV). At an individual level, the HED-affected patients were characterised by higher scores on the Verbal Comprehension Index, on Perceptual Reasoning and Working Memory Indices, and lower scores on the Processing Speed Index. As all of the Indices were within normal limits for the study population, in the absence of major mental/motor disabilities these findings support the mainstream education of HED-affected children.

The persistence and predictive value at 3-5 years of age of three signs detected within the first 18 months of life were investigated: phasic stretch reflex in one or both gastrocnemius muscles, imbalance in passive axial tone with an excess of dorsal extension, and a ridge on the squamous sutures. Phasic stretch reflex and at least one of the other signs were found in 14 children during repeated assessments within the first 18 months. The progress of these children was compared with that of 14 matched controls who had repeatedly normal neurological assessments during the first 18 months in the same clinic in Paris. At the age 3-5 years all the children were then assessed blindly by the second author from a pediatric neurological viewpoint and by two psychologists and two psychomotor therapists as well. The parents of the affected children reported significantly more problems in motor/praxis skills, language development and attention. Abnormal neurological signs were also significantly more frequent than in the controls. Suboptimal cognition did not reach significance. The neurological inclusion criteria were still present at 3-5 years old in 86% (vs. respectively 100% and 93% during the first 18 months of life) of this small group of children, while the cranial suture sign was still present in only 28% (vs. 64%). Findings of these three signs during the first 18 months of life may help in predicting long-term neurobehavioral or long-term neuropsychological problems.

Autism is a pervasive developmental disorder (PDD) characterized by the association of communication and socialization impairments, and by repetitive stereotyped behaviours. The Minnesota Test of Affective Processing (MNTAP) was used to investigate the discrimination of face identities and face expressions by autistic children. Young children in the 6- to 10-year-old age range suffering from PDD were compared to paired normal children. When the expressions on faces remained neutral, autistic patients had more difficulty in distinguishing different faces than in matching the same facial identities in face pairs: they perceived different faces as being identical. However, recognition errors disappeared when expressions were changed together with face identity. When autistic children were asked to distinguish expressions, they discriminated better identity than difference, just as normal children do. Analysis of face and expression discrimination in terms of identity and difference is a novel approach for the understanding of the clinical features of autism. Autistic children seek sameness and use an atypical strategy to analyse human faces and expressions.

A longitudinal study of a child (MV) with developmental verbal dyspraxia was conducted to determine to what extent language development and motor performance in this clinical diagnosis followed a similar course of maturation. Patient MV was observed for two years from the age of 5 years and 6 months. Initially, this young patient exhibited unintelligible and atypical speech production (multiword utterances without consonants), delay in balance and coordination, and impairments in rhythmic tasks; but she was otherwise developing normally with no intellectual impairment or behavioral disorder. MRI scans showed moderately enlarged ventricles, a thin, incompletely myelinated corpus callosum and intact basal ganglia. Two years later, MV's performance was nearly normal only in comprehension aspects of language. In contrast, production aspects of language and speech and neuromotor development showed very little improvement after two years. These observations first suggest that development of receptive and expressive domains within language may be asynchronous, and that the progression of motor control of language appears to follow a parallel course to neuromotor development.