Autism spectrum disorders associated with chromosomal abnormalities

Autism spectrum disorders (ASDs) constitute a class of severe neurodevelopmental conditions with complex multifactorial and heterogeneous etiology. Despite high estimates of heritability, genetic causes of ASDs remain elusive, due to a high degree of genetic and phenotypic heterogeneity. So far, several “monogenic” forms of autism have been identified, including Rett syndrome, Fragile-X syndrome, and Tuberous Sclerosis, accounting only for a small part of ASDs cases. Further evidences for rare mutations in the etiology of ASDs come from cytogenetic studies. Traditional cytogenetic approaches have highlighted the high frequency of large chromosomal abnormalities (about 7% of patients) and, more recently, the advent of high-resolution oligonucleotide microarrays has made possible to screen genome-wide for structural changes. In this review, we describe less known chromosomal abnormalities reported in association with ASDs and provide some clues to neuropediatricians for a more specific diagnostic evaluation of patients with ASDs.     

Autism associated with marker chromosome

Six boys who all showed the combination of moderate-severe mental retardation, autistic behavior, and mild-moderate physical stigmatization are described. Muscular hypotonia, epilepsy, and kyphoscoliosis were associated features in several cases, as were extremes of short stature and low weight. A supernumerary chromosome was found in all six cases, and it appears that there may be a separate syndrome associated with partial trisomy of chromosome 15.     

Comorbid psychiatric disorders in Arab children with Autism spectrum disorders

The objective of our study is to estimate the prevalence of comorbid psychiatric disorders in a sample of children with autism spectrum disorders (ASD) recruited from three Arab countries. We also examine the relationship between comorbidity and children's cognitive functioning and gender. Children who received a diagnosis of ASD (n = 60) from a child psychiatric outpatient clinic in Mansoura (Egypt), Al-Ahsa (Saudi Arabia) and Amman (Jordan) were included in this study. Comorbid diagnoses were established with a clinical interview and a semi-structured clinical interview for children and adolescents (SCICA). In addition, for all patients the cognitive evaluation was measured given the range in age and level of ability. Sixty-three percent of the children were diagnosed with at least one comorbid disorder. The most commonly reported comorbid disorders were anxiety disorders (58.3%), ADHD (31.6%), conduct disorders (23.3%), and major depressive disorder (13.3%). Out of the total sample, Obsessive compulsive disorder was the most prevalent anxiety disorder (55%). Elimination disorders were also diagnosed in 40% of patients. These findings emphasize a wide variety of psychiatric comorbidity afflicting youth with ASD and may be important targets for intervention.     

Autism spectrum symptoms in children with neurological disorders

Background

The behaviours of non-suicidal self-injury (NSSI) and deliberate self-harm (DSH) are prevalent among adolescents, and an increase of rates in recent years has been postulated. There is a lack of studies to support this postulation, and comparing prevalence across studies and nations is complicated due to substantial differences in the methodology and nomenclature of existing research.

Methods

We conducted a systematic review of current (2005 - 2011) empirical studies reporting on the prevalence of NSSI and DSH in adolescent samples across the globe.

Results

Fifty-two studies fulfilling the inclusion criteria were obtained for analysis. No statistically significant differences were found between NSSI (18.0% SD = 7.3) and DSH (16.1% SD = 11.6) studies. Assessment using single item questions led to lower prevalence rates than assessment with specific behaviour checklists. Mean prevalence rates have not increased in the past five years, suggesting stabilization.

Conclusion

NSSI and DSH have a comparable prevalence in studies with adolescents from different countries. The field would benefit from adopting a common approach to assessment to aide cross-cultural study and comparisons.     

Autism spectrum disorders in institutionalized subjects

Childhood maltreatment is delicate to assess both in clinical work and in research. There is a need for assessment tools that can be easily administered in an ethical and non-intrusive way that meets requirements of conceptual validity for various types of maltreatment and is sensitive to levels of severity. This study explores the psychometric properties of the Swedish translation of one such tool—the Childhood Trauma Questionnaire—Short Form (CTQ-SF; Bernstein and Fink, 1998). The CTQ-SF was administered to seven samples (total n=659)—five clinical samples and two non-clinical student samples. The factor structure supports the construct validity of the global maltreatment scale, four of the five maltreatment subscales (emotional abuse, physical abuse, sexual abuse and emotional neglect) and the minimization/denial (MD) scale, but not the physical neglect (PN) subscale. All items are highly correlated with their respective subscale. The discriminant validity is satisfactory. Highly significant correlation with social desirability gives further support for the MD-scale and to the recommendation of how to apply it. Internal consistency of PN is acceptable and for all other scales satisfactory. Swedish norm groups tend to score lower than similar American norm groups on abuse scales but higher on the neglect scales. Percentiles for seven gender-specific norm groups are presented. The weaknesses of the PN-scale are discussed and new constructs are proposed. The Swedish version of the CTQ-SF has the same construct validity and internal consistency as the original, including less homogeneity of the PN scale.     

Autism spectrum disorders: concurrent clinical disorders

Individuals with autism spectrum disorder are heterogeneous in clinical presentation, concurrent disorders, and developmental outcomes. This study characterized the clinical co-occurrences and potential subgroups in 160 children with autism spectrum disorders who presented to The Autism Center between 1999 and 2003. Medical and psychiatric co-occurrences included sleep disorders, epilepsy, food intolerance, gastrointestinal dysfunction, mood disorder, and aggressive and self-injurious behaviors. Sleep disorders were associated with gastrointestinal dysfunction (P < .05) and mood disorders (P < .01). Food intolerance was associated with gastrointestinal dysfunction (P = .001). Subjects with mood disorder tended to develop aggressive or self-injurious behaviors (P < .05). Developmental regression was not associated with increased co-occurrence of medical or psychiatric disorders. Medical co-occurrence did not present as a risk factor for psychiatric co-occurrence, and vice versa. These results showed a high prevalence of multiple medical and psychiatric co-occurrences. There may be common pathophysiologic mechanisms resulting in clinical subgroups of autism spectrum disorders. Recognition of the co-occurrence of concurrent disorders may provide insight into the therapeutic strategy.     

Autism spectrum disorders in children with normal intellectual levels: associated impairments and subgroups

In order to define potential subgroups pertaining to the spectrum of 'high-functioning' pervasive developmental disorders (PDDs) the medical and psychiatric records of 101 children with PDD were reviewed. Ninety-one children had a diagnosis of Asperger syndrome, nine had a PDD not otherwise specified, and one had 'high-functioning' autism. Mean age of the children (71 males, 30 females) was 9 years 8 months (age range 5 to 12 years). Apart from the core dysfunctions of the PDD, i.e. deficient social interaction, communication and repertoires, and restricted interests, 95% had attentional problems, 75% had motor difficulties, 86% had problems with regulation of activity level, and 50% had impulsiveness. About three-quarters had symptoms compatible with mild or severe attention-deficit-hyperactivity disorder (ADHD) or had deficits in attention, motor control, and perception (DAMP), indicating a considerable overlap between these disorders and high-functioning PDD in children of normal or near-normal intelligence. A combination of affective dysregulation, thought disturbance, and severely restricted social interaction, referred to as a multiple complex developmental disorder (MCDD; a condition possibly related to schizoaffective disorder), was recorded in about 8% of the children. Seventeen percent had another major medical diagnosis or medical syndrome, which highlights the importance of completing a neurological assessment of all children with PDDs.     

Sex differences in Arab children with Autism spectrum disorders

Although autism spectrum disorders (ASD) prevalence is higher in males than females in Arab countries, few studies address sex differences in autistic symptoms and coexiting behavioral problems. A total of 37 boys and 23 girls recruited from three Arab countries (Egypt, Saudi Arabia, Jordan) matched for age and IQ. They were compared using Indian Scale for Assessment of Autism (ISAA) and the Child Behavior Checklist (CBCL). The boys had poor emotional responsiveness and the girls had more cognitive problems. With regard to coexisting psychopathology boys exhibited significantly more delinquent behavior problems. Longitudinal, representative studies are needed to elucidate etiological significance of the observed sex differences.     

Social anxiety in adult males with autism spectrum disorders

BackgroundPsychiatric conditions, notably anxiety, commonly co-occur with autism spectrum disorders (ASD).MethodThis study investigated self-reported behavioural, cognitive and affective symptoms of social anxiety (SA) in 50 adult males with ASD. Associations between SA, core ASD symptoms and facets of neuropsychological functioning were also examined.ResultsTwenty-six participants (52%) endorsed levels of SA that exceeded the suggested caseness threshold for social anxiety disorder. Categorical and dimensional data analyses indicated that there were no relationships between SA symptoms, present-state or childhood ASD symptom-severity, or measures of socio-emotional processing in this sample.ConclusionsStudy findings suggest that severity of SA is not merely a reflection of ASD symptom-severity. Further research is needed to ascertain the prevalence of SA in adult ASD epidemiological samples, and identify causal and maintaining mechanisms for these co-morbid symptoms.     

Autism spectrum traits in children with mood and anxiety disorders

The autism spectrum disorders (ASDs) can present with symptoms commonly found in mood and anxiety disorders. The Social Communication Questionnaire (SCQ), Children's Communication Checklist (CCC-2), and the Social Reciprocity Scale (SRS) were used to screen children in a mood disorders research clinic setting for symptoms of ASD. Ninety-three patients (mean age, 12.7 +/- 2.8 years; percent male, 63%) completed at least one scale, and 50 children completed all three. The prevalence of those screening positive for a possible ASD on one instrument was 62% and on all three measures was 8%. Fifty-seven percent (n = 21/37; odds ratio, 4.59 [95% confidence interval (CI) = 1.40-15.11]) of those scoring in the "ASD-likely" range on the SRS scored in that range on the CCC-2. Only 16% (n = 6/37; odds ratio, not significant (NS)) of those scoring in the ASD-likely range on the SRS, and 14% (n = 5/37; odds ratio, NS) of those scoring in the ASD-likely range on the CCC-2, scored similarly on the SCQ. These results demonstrate a need to develop valid and reliable instruments to screen for ASDs in children presenting outside of ASD clinics.     

Autism spectrum disorders in children and adolescents with Moebius sequence

Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups. The primary caregivers of all children and adolescents with Moebius sequence aged 6–17 years known to the German Moebius foundation were anonymously asked to complete two screening measures of ASD [Behavior and Communication Questionnaire (VSK); Marburger Asperger’s Syndrome Rating Scale (MBAS)]. For those who reached the cut-off for ASD, well standardized diagnostic instruments (Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, WISC-III, and Kinder-DIPS) should be administered. Minimal diagnostic criteria for Moebius sequence were congenital facial weakness (uni- or bilateral) and impairment of ocular abduction (uni- or bilateral). Familiar cases should be excluded. The primary caregivers of 35/46 children and adolescents (18 males, 17 females, mean age 11.5 years) sent back completed questionnaires, but only 27 subjects met inclusion criteria. According to the primary caregivers, none of these subjects showed mental retardation. Two probands (both males 9 and 16 years old) reached the cut-off of the MBAS whereas the results of the VSK did not indicate ASDs in any of the patients. The 9 year old boy could be examined personally and did not meet diagnostic criteria of ASD. ASDs might be not as frequent as reported in previous studies on patients with Moebius sequence, at least not in patients without mental retardation.     

Autism spectrum disorders are prevalent among patients with dystrophinopathies

Recent studies have reported a higher prevalence of autism spectrum disorders among patients with dystrophinopathies. The aim of this study was to investigate the prevalence of autism spectrum disorder (ASD) among those with dystrophinopathies. The possible role of dystrophin isoforms in patients was also explored. Fifty-six patients recruited from Toneyama National Hospital were included in this study (mean age?=?12.9 years, SD?=?5.2 years). Autistic symptoms were evaluated using the Pervasive Developmental Disorders/Autism Spectrum Disorders Rating Scale (PARS), a clinician rating scale. Eleven patients (19.6%; 95% confidence interval 10.2–32.4) met the criteria for ASD based on their PARS scores. Patients were separated into two groups based on the cumulative loss of dystrophin isoforms predicted from the mutation location. The prevalence of ASD was examined between these groups. Infantile and current autistic symptoms did not differ between the groups, except on one subscale of the PARS. This study revealed that there was a high prevalence of ASD in patients with dystrophinopathies.     

Autism spectrum disorders in Down syndrome: A review

While it had been claimed that the association of autism spectrum disorders (ASDs) and Down syndrome was uncommon there are now a substantial number of studies demonstrating that a subgroup of those with Down syndrome will also reach the diagnostic criteria for an ASD. This review examines published research on the prevalence of ASDs in Down syndrome. The manifestation of ASDs in the Down syndrome population is also examined with regard to published case studies and profiles on ASD screening and diagnostic instruments. Possible correlates of ASDs in Down syndrome including level of cognitive functioning, medical factors, gender, and family history are also reviewed. Issues regarding the diagnostic assessment of ASDs in Down syndrome and suggestions for future research are discussed.     

Myopathy associated with neuromyelitis optica spectrum disorders

Neuromyelitis optica spectrum disorders (NMOSD) were generally thought to affect only central nervous system and spare peripheral aquaporin-4 (AQP4)-expressing organs. In recent years, however, increasing evidence has shown that skeletal muscle is involved in NMOSD. We provided a comprehensive review of the relevant literature and summarized the clinical and pathological characteristics of myopathy associated with NMOSD. NMOSD-associated myopathy seems to be characterized by mild muscle symptoms with prominent hyperCKemia and minimal changes on conventional pathological staining. Loss of AQP4 and deposition of IgG and activated complement products on sarcolemma of type II fibers are diagnostic features on immunohistochemical examinations. Creatine kinase leakage as a result of AQP4-IgG-induced, complement-mediated sarcolemmal injury may be a potential mechanism for hyperCKemia. Myopathy should be considered a component of NMOSD unified by AQP4-IgG seropositivity.     

Congenital anomalies associated with autism spectrum disorders

This study examined whether major congenital structural anomalies identified in infancy occurred more frequently in children later diagnosed with autism spectrum disorders (ASD; n=417; 341 males, 76 females) than in comparison children (n=2,067; 1,681 males, 386 females). Participants were sampled from infants born at Kaiser Permanente Northern California facilities between 1995 and 1999 who remained health plan members for at least 2 years (n=88,163). Comparison children were frequency-matched to children with ASD according to sex, birth year, and birth hospital. Congenital anomalies were diagnosed in 10.8% of children with ASD and 6.2% of comparison children (crude odds ratio [ORc] 1.8, 95% confidence interval [CI] 1.3-2.6). This association remained significant after adjustment for key maternal and infant covariates (adjusted OR [ORa] 1.7, 95% CI 1.1-2.4). Almost all organ-system anomaly categories were more prevalent in children with ASD, however only gastrointestinal anomalies were significantly associated with ASD in adjusted analyses (1.9 vs 0.4%, ORa 5.1, 95% CI 1.8-14.1).