Incontinence in autism spectrum disorder: a systematic review.

Autism spectrum disorders (ASD) are defined by persistent deficits in reciprocal social interaction, communication, and language, as well as stereotyped and repetitive behavior. Functional incontinence, as well as ASD are common disorders in childhood. The aim of this systematic review was to give an overview of the co-occurrence of nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) in ASD, and vice versa, of ASD in children with incontinence. A systematic literature search of the terms "incontinence", "enuresis", and "encopresis" in combination with "autism" or "Asperger" in four databases (Scopus, PubMed, PsycInfo and Web of science) was conducted. All studies that examined incontinence frequencies in samples with ASD, and studies that measured frequencies of ASD diagnoses or symptoms in samples with incontinence were included. Risk of bias and limitations of each study were described. After eligibility assessment, 33 publications were included in the review. The published literature implies a higher prevalence of incontinence in children with ASD compared to typically developing children. Limitations and biases as inappropriate diagnostic criteria for ASD and incontinence, selected samples, or lack of control groups are reported. Associations of incontinence in ASD with psychopathological symptoms were found. Vice versa, ASD symptoms are found in incontinent children, but no study included a non-ASD control sample. Incontinence symptoms are also reported as an adverse effect of medication in ASD. Due to methodological problems and definitional discrepancies in some publications, results have to be interpreted cautiously. Research in ASD and incontinence is scarce. More systematic research including state-of-the-art assessments is needed.

Standard urotherapy as first-line intervention for daytime incontinence: a meta-analysis.

According to the International Children's Continence Society (ICCS) guidelines for the treatment of daytime urinary incontinence (DUI) in children and adolescents, the first-line intervention for all types of DUI is standard urotherapy (SU). Despite this recommendation there is still no meta-analysis available on the effectiveness of SU. The aim of this study is to provide a meta-analytic evaluation of the intervention. This meta-analysis is based on Odds Ratios (OR) and consists of 26 patient samples out of 19 studies (N = 1609), collected from well-established medical databases. Remission rates after SU are compared to spontaneous remission rates, which are matched to the individual follow-up period. The meta-analysis shows that SU is an effective treatment of DUI. Compared to a spontaneous remission rate of 15.40% per year, urotherapy increases the probability to recover by a factor of 7.27 (6.57 if corrected for publication bias). After exclusion of three outlying samples this effect can be generalized for all types of SU and all patient populations. Moderator analyses cannot identify variables which significantly influence the variance of effect sizes. However, RCTs seem to be associated with lower effects, even when the control group is not considered for effect size calculation. Based on the present meta-analysis, SU is an effective intervention for treating DUI in children and adolescents. Of 100 patients in 1 year, approximately 56 patients (54 if corrected for publication bias) remit after being treated with SU, while only 15 out of 100 remit spontaneously. However, to further quantify the effect size of SU in comparison to spontaneous remission rates and other treatments, additional RCTs are still needed.

Incontinence in persons with Angelman syndrome.

Angelman syndrome (AS) is a congenital syndrome with a prevalence of 1:15,000. Individuals with AS often have severe intellectual disability, typical dysmorphic signs, and behavioral problems. The aim of the study was to investigate the rate of incontinence and associated psychological problems in children and adults with AS. Ninety children (4-18 years) and 54 adults (18-31 years) with AS were recruited through a parent support group (55.6% male, mean age 15.1 years). The Parental Questionnaire: Enuresis/Urinary Incontinence, the Incontinence Questionnaire-Pediatric Lower Urinary Tract Symptoms (ICIQ-CLUTS), as well as the Developmental Behaviour Checklist for parents (DBC-P) or for adults (DBC-A) were filled out by parents or caregivers. 85.6% of individuals with AS were affected by at least one subtype of incontinence (82.7% nocturnal enuresis (NE), 64.7% daytime urinary incontinence (DUI), and 57.1% fecal incontinence (FI)). 52.5% of the children and 32.6% of adults reached a clinically relevant DBC score. Incontinence was not associated with behavioral problems. NE and DUI were associated with genotype and epilepsy. CONCLUSION: Children with AS have high rates of incontinence. Many adults are still affected by NE, DUI, or even FI. Screening, assessment, and treatment of incontinence in individuals with AS are recommended. What is Known: • Incontinence in persons with Angelman syndrome (AS) is associated with younger age, lower level of adaptive functioning, and epilepsy. What is New: • Children and teens with AS are at special risk for incontinence, but older persons are also affected. • Comorbid epilepsy is significantly associated not only with nocturnal enuresis (NE) but also with daytime urinary incontinence (DUI). Underlying genotype is significantly associated with incontinence.

Stress and coping in parents of children and adolescents with spinal muscular atrophy.

BACKGROUND: Chronic illness and disability is not only associated with higher rates of behavioural problems in children, but also parental stress which requires active coping. The aim of the study was to analyse stress and coping, as well as their mediating variables, in parents of children and adolescents with Spinal Muscular Atrophy (SMA). METHOD: 96 children and adolescents with SMA aged 6;0 to 18;11 years were compared to 59 age, sex and SES matched controls. RESULTS: Parental stress was measured with the QRS, coping with the F-COPES and social support with the F-SOZU questionnaires.Parental stress was significantly higher in the SMA families for the total score and all subscales of the QRS. Stress was higher in families with severely affected SMA types I and II. The greatest percentage of variance contributing to stress could be explained by lack of social support, degree of disability and behavioural problems in the child. Although social support was reduced, the actual coping abilities of the families did not differ. CONCLUSION: Families with children and adolescents with SMA show high degrees of stress and strain which are associated with the severity of the disease, reduced social support and child behaviour. Despite these stresses they manage and cope no differently from families with healthy children.

Association of attention deficit and elimination disorders at school entry: a population based study.

PURPOSE: Attention deficit/hyperactivity disorder is a common comorbid disorder in children with nocturnal enuresis, daytime urinary incontinence and fecal incontinence. We assessed the specific association of these conditions in a population based sample. We hypothesized that children with elimination disorders have a higher rate of attention deficit/hyperactivity disorder, and that children with daytime urinary incontinence are more strongly affected than those with nocturnal enuresis. MATERIALS AND METHODS: All children in a defined geographic area (Saarpfalz Kreis) were examined at school entry. Mean age was 6.22 years in 734 boys and 6.18 years in 645 girls. A questionnaire regarding elimination problems and the attention problems scale of the Child Behavior Checklist were administered as an interview to parents. Participation rate was 99.1% (1,379 parents). RESULTS: Of the children 71 (5.1%) had attention deficit/hyperactivity disorder problems of clinical relevance (7.1% of boys and 2.9% of girls). A total of 185 children (13.4%) were wet (nocturnal enuresis in 9.1% and daytime urinary incontinence in 4.4%) and 19 (1.4%) had fecal incontinence. Attention deficit/hyperactivity disorder symptoms were more common in children with urinary incontinence than nonwetting children (16.8% vs 3.4%). When controlled for confounding variables, only children with daytime urinary incontinence (but not nocturnal enuresis) had a significantly higher risk of attention deficit/hyperactivity disorder symptoms (OR 4.4). CONCLUSIONS: Attention deficit/hyperactivity disorder symptoms were increased in children with urinary incontinence in this population based sample. Children with daytime urinary incontinence were at greater risk for attention deficit/hyperactivity disorder than those with nocturnal enuresis. Screening and referral for specialized treatment of both disorders are recommended.

Central nervous system processing of emotions in children with faecal incontinence.

AIM: Faecal incontinence (FI) is a common disorder involving both the enteric (ENS) and central nervous systems (CNS). The aim of the study is to analyze neurophysiologically the central processing of emotions in children with FI, healthy controls and children with Attention-deficit hyperactivity disorder (ADHD). METHODS: Fourteen children with FI and constipation, nine with non-retentive FI, 15 controls and 13 children with ADHD were examined. The methods included a physical exam, sonography, Child Behavior Checklist, a psychiatric interview and intelligence test. Acoustic evoked potentials were recorded according to standardized methodology. For the event-related potentials, 80 neutral, 40 positive and 40 negative pictures from the International Affective Picture System (IAPS), and 40 pictures depicting faeces were presented. RESULTS: Children with FI had significantly more intense responses for most stimuli over the frontal, central and parietal regions compared to controls. Stool pictures did not evoke stronger responses than other stimuli. Children with constipation elicited stronger responses. Children with ADHD did not differ from controls. Acoustic evoked potentials were comparable in all groups. CONCLUSIONS: Children with FI have increased responses in the processing of emotions. These can be interpreted as a neurobiological vulnerability, possibly due to the association of the ENS and CNS.

Fragile x syndrome and elimination disorders in a 6-year-old girl.

A case of a 6-year-old girl with multiple elimination disorders (nocturnal enuresis, functional urinary incontinence and fecal incontinence) and a fragile X-syndrome is described. The late diagnosis of the fragile X-syndrome had implications for treatment as well as for family interaction. With the knowledge of the diagnosis the parents reacted in a more understanding manner regarding the behavioral problems of the child, whereby the elimination problems were reduced. The need for further research on elimination disorders in children with genetic disorders is discussed.

Evaluation of a bladder and bowel training program for therapy-resistant children with incontinence.

INTRODUCTION: Daytime urinary incontinence (DUI) and fecal incontinence (FI) are common disorders in children. Although standard treatment is highly effective, subgroups of incontinence (combinations of nocturnal enuresis (NE), DUI and/or FI, or with psychological comorbidity) can relapse or take a chronic course. For these complex, therapy-resistant cases, a manualized outpatient bladder and bowel training program was developed. The aim of the study was to evaluate prospectively treatment effects of this training program, including a follow-up assessment. MATERIAL & METHODS: The training program was developed for small groups of 2-6 children (of same age and sex) aged 5-12 years with adaptations for 13-16 year-old adolescents. It consists of 7-9 weekly sessions for group training and 3 weekly sessions for individual training. The training comprises information about anatomy/physiology of the urogenital tract, pathophysiology, hygiene and balanced nutrition. Voiding and drinking diaries, stress management, relaxation and emotion regulation techniques are also included. Data of 32 children (mean age 8.6 years, range 5-13 years; 21 boys), who had received standard treatment (and did not reach complete response) are presented. 14 children received group therapy, 18 (younger children) were treated individually. Children were assessed before and after the treatment, as well as at a follow-up of 6 months later. Treatment effects were measured by incontinence frequency and treatment success according to the ICCS (complete response: 100% reduction of symptoms; partial response: 50-99% reduction of symptoms). Psychological symptoms were measured by the Child Behavior Checklist questionnaire (CBCL). RESULTS: Frequencies of DUI were significantly reduced from 5.7 wetting episodes/week (before training) to 4.9 (after training) to 2.0 (6 months after training). Frequencies of FI were reduced from 2.9 soiling episodes/week (before training) to 1.9 (after training), but increased to 2.6 (6 months after training). According to the ICCS classification, 11.1% of children with DUI had a complete response after training and 47.6% at follow-up after 6 months. In children with FI, 33.3% reached a complete response at the end of the training and 25% at follow-up. Additionally, psychological symptoms, especially internalizing, decreased significantly during training. Further, in 14 children with comorbid NE, nighttime wetting reduced from 5.9 before training to 1.5 episodes/week at follow-up. CONCLUSIONS: This bladder and bowel training program is an effective and successful treatment option for children with therapy-resistant subtypes of incontinence. Symptoms still improved 6 months after training in DUI. Additionally, the training program is helpful to decrease psychological symptoms.

Definitions, indications and practice of urotherapy in children and adolescents: - A standardization document of the International Children's Continence Society (ICCS).

BACKGROUND: Urotherapy is an umbrella term for all non-surgical, non-pharmacological interventions for lower urinary tract disorders (LUTD) in children and adolescents. Urotherapy is a specialized practice, which has become mainstay therapy not only for daytime urinary incontinence, but also for nocturnal enuresis, functional constipation and fecal incontinence. The aim of urotherapy is to achieve the normalization of the micturition and bowel pattern and to prevent further functional disturbances by repeated training. It is well known that in the treatment of adult and childhood incontinence a team approach is best, where there are shared areas of expertise and also discipline-specific expertise available. AIM: We present a consensus view from a cross-professional team of experts affiliated with the International Children's Continence Society on definitions, indications and practice of urotherapy. This is a selective, non-systematic review with practical recommendations for the implementation and research on urotherapy. METHODS: The document uses the globally accepted ICCS terminology. Evidence-based literature serves as the basis, but in areas lacking in primary evidence, expert consensus is used. Before submission, a full draft was made available to all ICCS members for additional comments. RESULTS: Urotherapy uses non-pharmacological, non-surgical methods and focuses on behavioral interventions, largely based on cognitive-behavioral psychotherapy (CBT). Standard urotherapy comprises components such as provision of information, instructions, life-style advice, counselling and registration of symptoms. Specific urotherapy is tailored towards specific disorders and includes alarm treatment, biofeedback training, pelvic floor training, neurostimulation and other interventions. Fig. 1. Urotherapy is a treatment that addresses all aspects of incontinence, leading to the best clinical outcome. This includes somatic, psychosocial, and behavioral problems and quality of life. Therefore urotherapy is recommended by the ICCS as the first-line treatment for most types of LUTD. The document is intended to be clinically useful in primary, secondary and tertiary care.

The natural history of daytime urinary incontinence in children: a large British cohort.

AIM: Few studies have looked at the prevalence of daytime incontinence in a longitudinal cohort of children. This study set out to determine the prevalence of daytime incontinence and relationships between daytime incontinence and bedwetting, faecal incontinence and urgency in a large cohort of British children. METHODS: Parents of children taking part in the Avon Longitudinal Study of Parents and Children (ALSPAC) were asked questions concerning the child's daytime wetting, bedwetting and faecal incontinence at different time points, 4.5, 5.5, 6.5, 7.5 and 9.5 years. The difference between the sexes for these different conditions was compared. RESULTS AND LIMITATIONS: Data were available for 10 819 of the 13 973 children who entered the study. The prevalence of any daytime incontinence declined from 15.5% at 4.5 years to 4.9% at 9.5 years, and was mainly described as infrequent. Daytime incontinence was more common in girls than boys and frequent (DSM-IV) incontinence was more commonly related to urgency, bedwetting and faecal incontinence than infrequent incontinence. CONCLUSIONS: Daytime incontinence is relatively common among children of primary school age and frequent incontinence more commonly coexists with other conditions, such as bedwetting and urgency. This study suggests the need for treatment to focus on children with frequent incontinence.

Quality of life and self-esteem for children with urinary urge incontinence and voiding postponement.

PURPOSE: Urge incontinence and voiding postponement are common subtypes of daytime wetting in children. We analyzed health related quality of life for children with urge incontinence and voiding postponement, and healthy controls at 2 centers. MATERIALS AND METHODS: We examined a total of 49 consecutive children 5 to 13 years old who presented with urge incontinence (22) or voiding postponement (27), and 32 controls matched for age and sex. Health related and overall quality of life were measured with generic questionnaires, and self-esteem was measured with the Piers-Harris questionnaire. RESULTS: Health related quality of life was significantly reduced in parent rating but not in child rating in the incontinent vs control group (total mean parent score 73 vs 78, child 76 vs 76). Children with voiding postponement have the lowest health related quality of life. Overall quality of life was significantly reduced in children with incontinence, while self-esteem did not differ. Children with externalizing disorders generally have the lowest health related and overall quality of life. CONCLUSIONS: Health related and overall quality of life are useful constructs, and are reduced in children with daytime incontinence by parental rating. In comparison, children rate their quality of life as being higher. Quality of life is lowest with externalizing behavioral disorders, as in children with voiding postponement. Due to comorbid behavioral disturbances, children with voiding postponement often need additional assessment, counseling and treatment.

Methylation mosaicism of 5'-(CGG)(n)-3' repeats in fragile X, premutation and normal individuals.

Fragile X syndrome (FRAXA) is characterized at the molecular level by an expansion of a naturally occurring 5'-(CGG)(n)-3' repeat in the promoter and 5'-untranslated region (5'-UTR) of the fragile X mental retardation (FMR1) gene on human chromosome Xq27.3. When expanded, this region is usually hypermethylated. Inactivation of the FMR1 promoter and absence of the FMR1 protein are the likely cause of the syndrome. By using the bisulfite protocol of the genomic sequencing method, we have determined the methylation patterns in this region on single chromosomes of healthy individuals and of selected premutation carriers and FRAXA patients. In control experiments with unmethylated or M- Sss I-premethylated DNAs, this protocol has been ascertained to reliably detect all cytidines or 5-methylcytidines as unmethylated or methylated nucleotides, respectively. Analyses of the DNA from FRAXA patients reveal considerable variability in the lengths of the 5'-(CGG)(n)-3' repeats and in the levels of methylation in the repeat and the 5'-UTR. In one patient (OEl) with high repeat length hetero-geneity ( n = 15 to >200), shorter repeats (n = 20-80) were methylated or unmethylated, longer repeats ( n = 100-150) were often completely methylated, but one repeat with n = 160 proved to be completely unmethylated. This type of methylation mosaicism was observed in several FRAXA patients. In healthy females, methylated 5'-CG-3' sequences were found in some repeats and 5'-UTRs, as expected for the sequences from one of the X chromosomes. The natural FMR1 promoter is methylation sensitive, as demonstrated by the loss of activity in transfection experiments using the unmethylated or M- Sss I-premethylated FMR1 promoter fused to the luciferase gene as an activity indicator.

Management of functional nonretentive fecal incontinence in children: Recommendations from the International Children's Continence Society.

BACKGROUND: Fecal incontinence (FI) in children is frequently encountered in pediatric practice, and often occurs in combination with urinary incontinence. In most cases, FI is constipation-associated, but in 20% of children presenting with FI, no constipation or other underlying cause can be found - these children suffer from functional nonretentive fecal incontinence (FNRFI). OBJECTIVE: To summarize the evidence-based recommendations of the International Children's Continence Society for the evaluation and management of children with FNRFI. RECOMMENDATIONS: Functional nonretentive fecal incontinence is a clinical diagnosis based on medical history and physical examination. Except for determining colonic transit time, additional investigations are seldom indicated in the workup of FNRFI. Treatment should consist of education, a nonaccusatory approach, and a toileting program encompassing a daily bowel diary and a reward system. Special attention should be paid to psychosocial or behavioral problems, since these frequently occur in affected children. Functional nonretentive fecal incontinence is often difficult to treat, requiring prolonged therapies with incremental improvement on treatment and frequent relapses.

Incontinence in children with autism spectrum disorder.

INTRODUCTION: Autism spectrum disorder (ASD) and incontinence (nocturnal enuresis (NE), daytime urinary incontinence (DUI), fecal incontinence (FI)) are relevant disorders in childhood. In general, children with special needs such as intellectual disability (ID) or ASD are more often affected by incontinence than typically developing children. OBJECTIVE: In the few studies conducted on children with ASD, gastrointestinal (GI) symptoms have received more attention than NE, DUI and lower urinary tract symptoms (LUTS). The aim of the present study was to assess the prevalence of incontinence, LUTS and psychological symptoms/disorders in children with ASD compared to controls. STUDY DESIGN: Forty children with ASD (12 children with infantile or childhood autism, 15 with atypical autism and 13 with Asperger's syndrome) (mean age 11.3 years) and 43 age-matched control children (mean age 10.7 years) were assessed. A questionnaire referring to incontinence and the International Consultation on Incontinence Questionnaire-Pediatric LUTS (ICIQ-CLUTS) were administered. Child psychopathology was assessed with the Child Behavior Checklist (CBCL/4-18). Child psychiatric ICD-10 diagnoses were based on a structured psychiatric interview (Kinder-DIPS). RESULTS: Children with ASD showed increased rates of NE (30.0% vs 0%) and DUI (25.0% vs 4.7%) compared to controls. Among children with ASD, daytime bladder control (≥5 years of age: 20.5% vs 0%) and bowel control (≥4 years of age: 42.5% vs 7.5%) were delayed compared to controls. Children with ASD had a higher LUTS score. Additionally, children with ASD were more often affected by psychological symptoms and disorders. Rates of clinically relevant externalizing symptoms (32.5% vs 0%), internalizing symptoms (67.5% vs 9.3%) and total problem score (70.0% vs 2.1%) were higher in children with ASD than the controls (see table). Children with ASD had more ICD-10 diagnoses than the controls (47.5% vs 4.7%). DISCUSSION: The present study showed that children with ASD are more at risk of DUI and NE than healthy controls. In addition, children with ASD had more LUTS, especially urgency and postponement, and they needed a longer time to become dry and continent. Additionally, according to the parental CBCL questionnaire, children with ASD showed higher rates of clinically relevant psychological symptoms (externalizing and internalizing symptoms), and according to the psychiatric interview, they had higher rates of comorbid psychological disorders. CONCLUSION: Autism spectrum disorder is an incapacitating disorder with significant impairment in social functioning. In most cases, psychological symptoms and disorders co-occur. Additionally, children with ASD are at a greater risk of being affected by different forms of incontinence and LUTS. Therefore, screening for incontinence and, if indicated, treatment of these disorders is recommended.

Incontinence in children with treated attention-deficit/hyperactivity disorder.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) and incontinence (nocturnal enuresis, daytime urinary incontinence and fecal incontinence) are common disorders in childhood. Both disorders are strongly associated with each other. OBJECTIVE: ADHD can affect compliance to incontinence therapy in a negative way; it can also affect outcome. The aim of the present study was to assess the prevalence of incontinence, age of bladder and bowel control, and psychological symptoms in children having treatment for ADHD compared to a control group. STUDY DESIGN: Forty children having treatment for ADHD (75% boys, mean age 11.4 years) and 43 matched controls (60.5% boys, mean age 10.7 years) were assessed. Their parents filled out questionnaires to assess: child psychopathology (Child Behavior Checklist), incontinence (Parental Questionnaire: Enuresis/Urinary Incontinence; Encopresis Questionnaire - Screening Version) and symptoms of the lower urinary tract (International-Consultation-on-Incontinence-Questionnaire - Pediatric Lower Urinary Tract Symptoms). The ICD-10 diagnoses and children's IQ were measured by standardized instruments (Kinder-DIPS, Coloured Progressive Matrices/Standard Progressive Matrices). RESULTS: Rates of incontinence in the ADHD group (5% nocturnal enuresis, 5% daytime urinary incontinence, 2.5% fecal incontinence) did not differ significantly from incontinence rates in the control group (4.7% daytime urinary incontinence). More children in the ADHD group had Child Behavior Checklist scores in the clinical range. Further ICD-10 disorders were present in eight children with ADHD and in one control child. More children with ADHD had delayed daytime and nighttime bladder control, as well as delayed bowel control, than the controls. DISCUSSION: The present study showed that if children are treated for their ADHD, according to standard practice guidelines, incontinence rates are similar to those without ADHD. More children with ADHD reached continence at a later age than the controls, which could be an indicator of maturational deficits in the central nervous system. Additionally, children with ADHD showed higher rates of clinically relevant psychological symptoms. CONCLUSION: This study provides further information of the association between ADHD and incontinence. Treatment of ADHD may be associated with positive effects on incontinence outcomes. Therefore, children with ADHD should always be screened for incontinence problems and children with incontinence problems should also be screened for ADHD if symptoms of hyperactivity, inattention and/or impulsivity are also present.

Intelligence and cognitive function in children and adolescents with spinal muscular atrophy.

Spinal muscular atrophy is a chronic disease characterised by loss of motor function. The aim of the study was to analyse cognitive functions in a large group of patients with spinal muscular atrophy. It was hypothesised that their intelligence is comparable to controls, but not above average as previously postulated. Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests). The mean IQ measured with the CPM/SPM tests was 109.6 for the spinal muscular atrophy group, 107.3 for the sibs and 104.1 for the healthy controls (no significant difference). In the older children and adolescents (SPM only) the mean IQ was significantly higher for the spinal muscular atrophy patients (109.6) than for the controls (95.4). The standard score in the 'mental processing composite' scale of the Kaufman-ABC was identical in the spinal muscular atrophy group and controls (103.8). The cognitive profile was relatively homogeneous. However, the older children and adolescents did have a significantly higher verbal IQ (113.8) than controls (104.6) in the Wechsler tests. There were no significant differences in any of the tests among different grades of severity (spinal muscular atrophy types I-III). It can be concluded that children and adolescents with spinal muscular atrophy have a general intelligence in the normal range. By adolescence, environmentally mediated aspects of intelligence are higher in patients with spinal muscular atrophy. It could be speculated that the development of cognitive skills and knowledge is a creative way to compensate the many restrictions due to their physical handicap.

Cognitive and behavioral profile of fragile X boys: correlations to molecular data.

Fragile X syndrome (FXS) is the most common form of inherited mental retardation after Down syndrome. The expansion of a CGG repeat, located in the 5'-untranslated region (5'-UTR) of the FMR1 (fragile X mental retardation) gene, leads to the hypermethylation of the repeat and the upstream CpG island. Methylation is associated with transcriptional silencing of the FMR1 gene. The lack of FMR1 protein is believed to be responsible for the typical physical and mental characteristics of the syndrome. To analyze the specific phenotype of that syndrome as well as possible associations between the phenotype and the genotype, we examined a group of 49 fragile X boys and a control group of 16 patients with tuberous sclerosis. To determine the cognitive and behavioral phenotype, the Kaufman Assessment Battery for Children (K-ABC), the Child Behavior Checklist (4/18), and a structured psychiatric interview (Kinder DIPS) were used. The genotype was analyzed by the Southern blot method. The phenotype of boys with FXS is characterized by a specific cognitive profile with strengths in acquired knowledge and in simultaneous processing. The psychiatric comorbidity is high and ADHD (attention deficit hyperactivity disorder), oppositional defiant disorder, enuresis, and encopresis predominate. In a group of 24 fragile X boys, no significant correlations between the specific aspects of the phenotype and the genotype were found.

Association analysis of the dopamine D2 receptor gene in Tourette's syndrome using the haplotype relative risk method.

Comings et al. [1991: JAMA 266: 1793-1800] have recently reported a highly significant association between Tourette's syndrome (TS) and a restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene (DRD2) locus. The A1 allele of the DRD2 Taq I RFLP was present in 45% of the Tourette patients compared with 25% of controls. We tried to replicate this finding by using the haplotype relative risk (HRR) method for association analysis. This method overcomes a major problem of conventional case-control studies, where undetected ethnic differences between patients and controls may result in a false-positive finding, by using parental alleles not inherited to the proband as control alleles. Sixty-one nuclear families encompassing an affected child and parents were typed for the DRD2 Taq I polymorphism. No significant differences in DRD2 A1 allele frequency were observed between TS probands, subpopulations of probands classified according to tic severity, or parental control alleles. Our data do not support the hypothesis that the DRD2 locus may act as a modifying gene in the expression of the disorder in TS probands.

Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome.

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurrence of tic disorders and OCS might indicate heterogeneity of TS.

[Psychological and psychiatric aspects of nocturnal enuresis and functional urinary incontinence]. / Psychologisch-psychiatrische Aspekte der Enuresis nocturna und der funktionellen Harninkontinenz.

Psychological factors play an important role in nocturnal enuresis and functional urinary incontinence. The comorbidity of enuresis/urinary incontinence and clinical mental disorders as well as subclinical psychological symptoms is reviewed. In epidemiological as well as clinical studies, 20-40% of all children with nocturnal enuresis have a manifest clinical disorder-two to four times higher than nonwetting children. Children with secondary nocturnal enuresis and voiding postponement carry the highest risk for a mental disorder and those with urge incontinence and primary monosymptomatic nocturnal enuresis the lowest.Internalizing disorders (such as depressive and anxiety disorders) are less common than externalizing ones (such as ADHD). In addition, subclinical emotional and behavioral symptoms are common. These will often recede upon attaining dryness and self-esteem can increase. General screening for psychological symptoms and disturbances is recommended.