Are Psychiatrists Trained to Address the Mental Health Needs of Young People Transitioning From Child to Adult Services? Insights From a European Survey.

Background: In mental health, transition refers to the pathway of young people from child and adolescent to adult services. Training of mental health psychiatrists on transition-related topics offers the opportunity to improve clinical practice and experiences of young people reaching the upper age limit of child and adolescent care.

Methods: National psychiatrist's organizations or experts from 21 European countries were surveyed 1/ to describe the status of transition in adult psychiatry (AP) and child and adolescent psychiatry (CAP) postgraduate training in Europe; 2/ to explore the amount of cross-training between both specialties.

Clinical phenotypes of infantile onset CACNA1A-related disorder.

Background: CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events: epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients.

Objective: To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations.

FGF14-related episodic ataxia: delineating the phenotype of Episodic Ataxia type 9.

We report four patients from two families who presented attacks of childhood-onset episodic ataxia associated with pathogenic mutations in the FGF14 gene. Attacks were triggered by fever, lasted several days, and had variable frequencies. Nystagmus and/or postural tremor and/or learning disabilities were noticed in individuals harboring FGF14 mutation with or without episodic ataxia.

Training of adult psychiatrists and child and adolescent psychiatrists in europe: a systematic review of training characteristics and transition from child/adolescent to adult mental health services.

Background: Profound clinical, conceptual and ideological differences between child and adult mental health service models contribute to transition-related discontinuity of care. Many of these may be related to psychiatry training.

Methods: A systematic review on General Adult Psychiatry (GAP) and Child and Adult Psychiatry (CAP) training in Europe, with a particular focus on transition as a theme in GAP and CAP training.

Cognitive impairment in children with CACNA1A mutations.

Aim: To describe the clinico-radiological phenotype of children with a CACNA1A mutation and to precisely evaluate their learning ability and cognitive status.

Method: Children between the ages of 3 and 18 years harboring a pathogenic CACNA1A mutation associated with episodic ataxia, hemiplegic migraine, benign paroxysmal torticollis, benign paroxysmal vertigo, or benign paroxysmal tonic upgaze, were enrolled in this cross-sectional study. Data concerning psychomotor development, academic performance, educational management, clinical examination at inclusion, and brain imaging were collected.

Benign paroxysmal torticollis, benign paroxysmal vertigo, and benign tonic upward gaze are not benign disorders.

Aim: Benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) are characterized by transient and recurrent episodes of neurological manifestations. The purpose of this study was to analyse the clinical relationships between these syndromes, associated comorbidities, and genetic bases.

Method: In this cross-sectional study, clinical data of patients with BPT, BPV, or BTU were collected with a focus on developmental achievements, learning abilities, and rehabilitation.

Severe phenotypic spectrum of biallelic mutations in PRRT2 gene.

Background: Heterozygous dominant mutations of PRRT2 have been associated with various types of paroxysmal neurological manifestations, including benign familial infantile convulsions and paroxysmal kinesigenic dyskinesia. The phenotype associated with biallelic mutations is not well understood as few cases have been reported.

Methods: PRRT2 screening was performed by Sanger sequencing and quantitative multiplex PCR of short fluorescent fragments.

Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants.

Objective: Duchenne muscular dystrophy (DMD) is characterised by progressive muscle weakness. It has recently been reported that single nucleotide polymorphisms (SNPs) located in the SPP1 and LTBP4 loci can account for some of the inter-individual variability observed in the clinical disease course. The validation of genetic association in large independent cohorts is a key process for rare diseases in order to qualify prognostic biomarkers and stratify patients in clinical trials.

[Phenotypic heterogeneity and phenotype-genotype correlations in dystrophinopathies: Contribution of genetic and clinical databases].

The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies).

Comprehensive oligonucleotide array-comparative genomic hybridization analysis: new insights into the molecular pathology of the DMD gene.

We report on the effectiveness of a custom-designed oligonucleotide-based comparative genomic hybridization microarray (array-CGH) to interrogate copy number across the entire 2.2-Mb genomic region of the DMD gene and its applicability in diagnosis. The high-resolution array-CGH, we developed, successfully detected a series of 42 previously characterized large rearrangements of various size, localization and type (simple or complex deletions, duplications, triplications) and known intronic CNVs/Indels.

Motor and respiratory heterogeneity in Duchenne patients: implication for clinical trials.

Aims: Our objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD).

Methods: The French dystrophinopathy database provided clinical, histochemical and molecular data of 278 DMD patients (mean longitudinal follow-up: 14.2 years).

[Genetic mutation databases: stakes and perspectives for orphan genetic diseases].

New technologies, which constantly become available for mutation detection and gene analysis, have contributed to an exponential rate of discovery of disease genes and variation in the human genome. The task of collecting and documenting this enormous amount of data in genetic databases represents a major challenge for the future of biological and medical science. The Locus Specific Databases (LSDBs) are so far the most efficient mutation databases.

Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase.

UMD-DMD France is a knowledgebase developed through a multicenter academic effort to provide an up-to-date resource of curated information covering all identified mutations in patients with a dystrophinopathy. The current release includes 2,411 entries consisting in 2,084 independent mutational events identified in 2,046 male patients and 38 expressing females, which corresponds to an estimated number of 39 people per million with a genetic diagnosis of dystrophinopathy in France. Mutations consist in 1,404 large deletions, 215 large duplications, and 465 small rearrangements, of which 39.

Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy.

Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show intragenic deletions ranging from one to several exons of the DMD gene and leading to a premature stop codon. Other deletions that maintain the translational reading frame of the gene result in the milder Becker muscular dystrophy (BMD) form of the disease. Thus the opportunity to transform a DMD phenotype into a BMD phenotype appeared as a new treatment strategy with the development of antisense oligonucleotides technology, which is able to induce an exon skipping at the pre-mRNA level in order to restore an open reading frame.

Partial epilepsy and 47,XXX karyotype: report of four cases.

Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of the most common sex chromosome abnormalities in females, and is associated with considerable phenotypic variability. This report describes four 47,XXX females with mental deficiency and epilepsy.

[Parry-Romberg's syndrome and epilepsy].

Introduction: Parry-Romberg's syndrome or progressive facial hemiatrophy is a rare disorder of unknown etiology which may be accompanied by neurological complications, frequently epilepsy, usually focal refractory epilepsy. The associated brain lesions are located on the same side as the half face atrophy and may progress.

Observation: We report the cases of two patients with Parry-Romberg's syndrome and epilepsy.

[Movement disorders in childhood: therapeutic update].

Abnormal movements are not uncommon in childhood. Due to the severity of the abnormal movements or to the functional disability, a medical treatment is often required; the wide range of available pharmacological molecules and the absence of therapeutic consensus highlight the limited efficacy of the medical treatment on dystonic or athetoid movements, or severe tic disorders. The recent identification of the enzymatic defect implicated in metabolic diseases led to the development of specific treatment for newly recognized disorders, with more or less interesting results (creatine ou biotine supplementation).

[Movement disorders in childhood: classification and genetic update].

Abnormal movements are not unusual in childhood. Recent genetic progresses provide a new approach of childhood movement disorders. Several loci have been identified in paroxysmal dyskinesia, or in Gilles de la Tourette syndrome.

Ataxia with vitamin E deficiency and severe dystonia: report of a case.

Mutation of the gene for alpha-tocopherol transfer protein causes ataxia with isolated vitamin E deficiency, a disorder usually stabilized or improved after vitamin E supplementation. Dystonia has rarely been described in ataxia with isolated vitamin E deficiency (AVED) patients. We present the case of a young boy with AVED, whose neurological and extra-neurological cardinal symptoms of the disease improved after vitamin E supplementation but who progressively developed generalized dystonia.

Interictal paroxysmal epileptic discharges during sleep in childhood: phenotypic variability in a family.

We report three children of the same parents who exhibited various types of cognitive disorders, ranging from severe mental deficiency with transient autistic-like regression to specific neuropsychological disabilities, associated with paroxysmal EEG abnormalities with various patterns of severity. This familial association highly suggests a genetic factor responsible for both epileptic discharges on EEG and cognitive dysfunction.

[The varied etiologies of childhood-onset dystonia].

Dystonia is not uncommon in childhood, and identification of its etiology is an ultimate aim in the clinical evaluation of dystonia. Advances in neuroimaging, recent identification of gene or loci implicated in dystonic syndromes, and characterisation of new pathological entities (creatine deficiency, biotin-responsive basal ganglia disease) enlarge our understanding of childhood dystonia, and expend its diagnosis spectrum. Awareness of the diverse etiologic categories of childhood-onset dystonia is necessary to accurate diagnosis approach.

Neurological presentation of three patients with 22q11 deletion (CATCH 22 syndrome).

Chromosome 22q11 deletion (CATCH 22 syndrome or velocardiofacial syndrome) is one of the most frequent chromosomal syndromes. Neurological features other than cognitive disorders are probably the least-described part of the expanding phenotype of the 22q11 deletion. We report the neurological features of three unrelated children with a de novo deletion: one patient with an autistic disorder, a second patient with hypocalcaemic neonatal seizures and unusual persistent epileptic focus at electroencephalographic follow-up, and a third patient with atypical absence epilepsy.