Actualité de la prise en charge des mouvements anormaux chez l’enfant : la dystonie

2,48 x 1,25 x 1,05 metres de bronze.Díaz, Lautaro (escultor)Pla mig de l'obra. A la part superior d'unes escales que voregen la mar, hi ha un home i una dona de bronze asseguts plàcidament. El que li interessa és transmetre una sensació de tranquil·litat que inciti a contemplar el paisatge

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/ hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

The primary headaches: genetics, epigenetics and a behavioural genetic model

The primary headaches, migraine with (MA) and without aura (MO) and cluster headache, all carry a substantial genetic liability. Familial hemiplegic migraine (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is due to mutations in genes encoding neural channel subunits. MA/MO are considered multifactorial genetic disorders, and FHM has been proposed as a model for migraine aetiology. However, a review of the genetic studies suggests that the FHM genes are not involved in the typical migraines and that FHM should be considered as a syndromic migraine rather than a subtype of MA. Adopting the concept of syndromic migraine could be useful in understanding migraine pathogenesis. We hypothesise that epigenetic mechanisms play an important role in headache pathogenesis. A behavioural model is proposed, whereby the primary headaches are construed as behaviours, not symptoms, evolutionarily conserved for their adaptive value and engendered out of a genetic repertoire by a network of pattern generators present in the brain and signalling homeostatic imbalance. This behavioural model could be incorporated into migraine genetic research

Déficit moteur aigu non traumatique de l'enfant : orientations diagnostiques Acute motor deficit in childhood: Diagnosis management

International audienceAcute motor deficit is not uncommon in childhood, with various neurological etiologies. Pertinent semiological analysis allows correct diagnosis mangement, with adequate paraclinical investigations. The authors describe this clinical diagnosis strategy. The most common clinical situations and various etiologies are presented; paraclinical investigations confirming the diagnosis are discribed, with specific attention to central nervous system imaging according to the most recent sequences.La survenue d'un déficit moteur aigu d'un ou plusieurs membres n'est pas une situation exceptionnelle chez l'enfant. Les causes neurologiques en sont variées ; l'orientation étiologique nécessite une analyse sémiologique minutieuse, dont dépendent les investigations complémentaires ciblées. Les auteurs proposent de décrire cette démarche diagnostique à partir des données cliniques ; les principales situations cliniques et étiologies sont présentées ; les investigations complémentaires permettant de confirmer le diagnostic sont évoquées ; les données de l'imagerie du système nerveux obtenues, notamment grâce aux séquences les plus récentes, sont décrites

Myopathies constitutionnelles : place des examens complémentaires

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