[International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder]. / Internationale Konsenserklärung zu Screening, Diagnostik und Behandlung von Jugendlichen und Heranwachsenden mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung und gleichzeitigen Störungen durch Substanzgebrauch.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Abstract. Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder.

BACKGROUND: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. OBJECTIVE: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. METHOD: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. RESULTS: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. CONCLUSION: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for the development of substance abuse and substance use disorders (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment, and is associated with poor treatment outcomes. In this study, we provide a systematic review of controlled studies on the effectiveness of pharmacological, psychosocial, and complementary treatments of ADHD in adolescents with and without comorbid SUD. In addition, we review the longitudinal association between pharmacotherapy for childhood ADHD and the development of SUD in adolescence and early adulthood. We conducted a systematic review of the research literature published since 2000 using Medline, PsycINFO, and the Cochrane Database of Systematic Reviews databases to select randomized clinical trials, observational studies, and meta-analyses. The quality of the evidence from each study was rated using the SIGN grading system. Based on the limited evidence available, strong clinical recommendations are not justified, but provisionally, we conclude that stimulant treatment in children with ADHD may prevent the development of SUD in adolescence or young adulthood, that high-dose stimulant treatment could be an effective treatment for adolescents with ADHD and SUD comorbidity, that cognitive behavior therapy might have a small beneficial effect in these patients, and that alternative treatments are probably not effective. More studies are needed to draw definitive conclusions that will allow for strong clinical recommendations.

Morphological abnormalities in children with thyroidal congenital hypothyroidism.

Several groups of investigators have reported an increased incidence of congenital anomalies in patients with congenital hypothyroidism. Furthermore, in patients with congenital hypothyroidism and mutations in genes known to be involved in thyroid development, specific extra-thyroidal abnormalities have been observed. The goal of the present study was to gain insight in the types and patterns of morphological characteristics depending on the type of congenital hypothyroidism of thyroidal origin (CH-T). In 242 Dutch CH-T patients with a thyroid agenesis, a dystopic thyroid rudiment or a eutopic thyroid gland, we performed a careful physical examination of the body surface directed to visually detectable morphological abnormalities; results were compared to a group of 1,007 Dutch control subjects. The percentage of patients with one or more major abnormalities in the total CH-T cohort (33.1%) and in patients with CH-T dystopic thyroid (37.2%) was significantly higher than in the control population (21.8%; P < 0.001). Especially in the CH-T dystopic thyroid group specific major malformations (bilateral ear pits; oligodontia) were found more frequently. Also, the percentage of patients in the total CH-T group with one or more minor anomalies (96.3%) was significantly higher than in the control group (82.5%). The careful grouping of patients according to their CH-T etiology and the types and patterns in morphological findings may be helpful in the search for novel genes involved in thyroid development.

A novel 6.14 Mb duplication of chromosome 8p21 in a patient with autism and self mutilation.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with a strong genetic etiology. Cytogenetic abnormalities have been detected in 5-10% of the patients with autism. In this study, we present the clinical, cytogenetic and array-comparative genomic hybridization (array-CGH) evaluation of a 13-year-old male with severe developmental delay, facial dysmorphic features, autism and self mutilation. The patient was found to carry a de novo duplication of chromosome region 8p21 of minimally 6.14 and maximally 6.58 Mb as ascertained by bacterial artificial chromosome (BAC)-based array-CGH. Hitherto, only a few patients with autism with cytogenetically visible duplications involving the chromosome 8p21 region have been described, but the extent of these duplications has not been determined at the molecular level. This represents the smallest rearrangement of chromosomal region 8p21 as yet found in a patient with autism. For 11 of the 36 genes with known functions located within this duplication clear transcription in the brain was found. Of those the STMN4 and DPYSL2 genes are the most likely candidate genes to be involved in neuronal development, and, if altered in gene-dosage, in the autistic phenotype of our patient.

Prevalence and patterns of morphological abnormalities in patients with childhood cancer.

CONTEXT: Constitutional gene defects predispose to cancer in children. Such tumor predisposition syndromes can be recognized by specific patterns of morphological abnormalities. OBJECTIVES: To assess the prevalence of morphological abnormalities in a large cohort of patients with childhood cancer and to identify new tumor predisposition syndromes. DESIGN, SETTING, AND PARTICIPANTS: Patients were recruited from Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands, between January 2000 and March 2003. A total of 1073 patients underwent a physical examination directed at 683 morphological abnormalities. The patient cohort consisted of 898 long-term survivors of childhood cancer and 175 newly diagnosed pediatric patients with cancer. The control group consisted of 1007 schoolchildren examined in an identical way. Mean ages of patients and controls were 21.2 and 10.4 years, respectively. MAIN OUTCOME MEASURES: Prevalence and patterns of morphological abnormalities in patients compared with controls. To prevent age bias, only age-independent abnormalities were used for overall prevalence analysis. Patients younger than 9 years were excluded from the pattern analysis. The sample was restricted to white patients to prevent ethnicity bias. RESULTS: Morphological abnormalities were significantly more prevalent in pediatric patients with cancer. Major abnormalities were present in 26.8% of patients vs 15.5% of controls (P < .001) and minor anomalies in 65.1% of patients vs 56.2% of controls (P < .001). Three or more minor anomalies were detected in 15.2% of patients vs 8.3% in controls (P < .001). Forty-two patients were diagnosed with an established tumor predisposition syndrome. Multivariate analyses showed 14 morphological abnormalities to occur significantly more often in the patient group. For 2 of these (blepharophimosis and asymmetric lower limbs), we identified statistically significant patterns of co-occurring morphological abnormalities suggestive of new tumor predisposition syndromes. Thirty-four patients fit 1 of the 2 novel tumor predisposition patterns. CONCLUSIONS: Pediatric patients with cancer show a significantly higher prevalence of morphological abnormalities compared with controls. Specific patterns of morphological abnormalities indicate possible unrecognized tumor predisposition syndromes, but validation in an independent sample is needed.

Progeria: a new kind of Laminopathy-- report of the First European Symposium on Progeria and creation of EURO-Progeria, a European Consortium on Progeria and related disorders.

Progeria is a rare, genetically determined condition characterized by accelerated aging in children. Its name is derived from Greek (Geron) and means "prematurely old". The classic type is the Hutchinson-Gilford Progeria Syndrome (HGPS), which was first described in England in 1886 by Dr. Jonathan Hutchinson (1) and again in 1904 by Dr. Hastings Gilford (2). Since then and up to now, very little advancement toward the understanding of this devastating disorder has been accomplished. In early 2003 a French group succeeded in identifying point mutations in the LMNA gene, encoding A-type lamins, as the main cause of this disorder. These results were concomitantly confirmed by an American group, who identified mutations in LMNA, working on a large cohort of patients (3,4). HGPS is thus the most severe disorder added to the expanding list of "laminopathies", diseases caused by mutations in the LMNA gene encoding A-type lamins. To date, up to ten disorders are associated with mutations in LMNA. These disorders are diverse, both in their symptomatology and pattern of inheritance (see below and table 1). Due to the extremely low prevalence of progeria and the putative functional links between progeria and other premature aging disorders, setting-up a network about these disorders has become an absolute necessity. A reunion of families with a child affected with progeria, gathered within the European Progeria Family Circle, was held from September 25th to 29th 2003 in Magdeburg, Germany. In parallel to this event, a scientific symposium centered on clinical and molecular update of HGPS and related syndromes was organised. Several international experts, including clinical and molecular geneticists, cell biologists involved in the field of laminopathies, as well as paediatricians and other physicians with clinical experience in diagnosis, treatment and research on progeria and progeria-like syndromes presented their experience as well as their research projects and yet unpublished results. The main discussed topics as well as the developing research fields on progeria and related premature ageing disorders will be presented here.

Morphological features in children with autism spectrum disorders: a matched case-control study.

This study was designed to examine morphological features in a large group of children with autism spectrum disorder versus normal controls. Amongst 421 patients and 1,007 controls, 224 matched pairs were created. Prevalence rates and odds ratios were analyzed by conditional regression analysis, McNemar test or paired t-test matched pairs. Morphological abnormalities were significantly more prevalent in patients with autism than in the normal control group and 48 morphological features distinguished patients from controls. Our findings show that morphological features are associated with autism. Exploring potential underlying genetic mechanisms of this association might lead to a better understanding of autism.

Normal values for morphological abnormalities in school children.

Clinical morphology has proven to be a strong tool in the delineation of many syndromes and a helpful instrument in molecular studies. Numerous studies have been performed investigating the prevalence of minor anomalies in various disorders; all concluding that minor anomalies can well be utilized as indicators of altered embryonic differentiation. However, for adequate evaluation, normal values for phenotypic abnormalities are essential. So far, only few studies on the frequency of phenotypic abnormalities in the normal population have been done having one thing in common: all were performed in newborn infants. We studied morphological characteristics in a group of 1,007 school children, representative for the Dutch population, through a body surface examination using detailed definitions for all morphological findings. The region of study and distribution of children over various school types was chosen in such a way that it represented the general Dutch population. The median age of the studied children was 11 years (range 8-14 years), sex ratio (M:F) was 0.93. Nine hundred twenty-three children were of Caucasian descent, 84 others of mixed ethnic backgrounds. The reliability of the examinations was tested by independent scoring of 111 children by two observers, showing a kappa score of 0.85. Normal values for the morphological findings are presented together with their age-adjusted classification. These normal values provide a valuable source for validation of classifications of phenotypic abnormalities, especially those that are depending on frequency, that is, minor anomalies and common variants. Furthermore, they will allow a proper evaluation of patterns of phenotypic abnormalities found in patient groups with specific disorders.

Cerebellar hypoplasia-endosteal sclerosis: a long term follow-up.

Cerebellar hypoplasia with endosteal sclerosis is an infrequent entity that has been described in only four cases. Major clinical symptoms are cerebellar hypoplasia causing ataxia, hypotonia, mild to moderate developmental delay, microcephaly, growth retardation, endosteal sclerosis, tooth eruption disturbances, and hip dislocations. We report on a girl with this entity, whom we followed for 11 years. The endosteal sclerosis remained stationary over time, as were the clinical neurological symptoms, but neuroadiological symptoms were slowly progressive. We provide a short review of this probably autosomal recessively inherited disorder. (c) 2005 Wiley-Liss, Inc.