American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2010
Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic et... more Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used highresolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first-or second-degree relatives with an ASDrelated neuropsychiatric phenotype in comparison with cases without reported heredity (P ¼ 0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs.
Acta paediatrica (Oslo, Norway : 1992), Jan 6, 2015
Several studies have suggested that rare copy number variants (CNVs) are an important genetic con... more Several studies have suggested that rare copy number variants (CNVs) are an important genetic contributor to autism spectrum disorders. The aims of the study were to use chromosomal microarray to investigate the presence of rare copy number variants in a population-based cohort of well-characterised young children with autism spectrum disorders and to relate the genetic results to neurodevelopmental profiles and medical conditions. We performed chromosomal microarray on samples from 162 children who had been referred to the Stockholm Autism Centre for Young Children in Sweden after being diagnosed with autism spectrum disorder between 20 and 54 months of age. Pathogenic aberrations were detected in 8.6% of the children and variants of uncertain significance were present in another 8.6%. CNVs were more frequent in children with congenital malformations or dysmorphic features as well as in the subgroup with intellectual disability. Our results support the use of chromosomal microarray...
The aim was to characterize the panorama of developmental disorders in 208 preschool children wit... more The aim was to characterize the panorama of developmental disorders in 208 preschool children with a clinical diagnosis of autism spectrum disorder (ASD), referred to a specialized centre, the Autism Centre for Young Children (ACYC), for intervention. At the centre, a research team examined all children according to structured protocols and interviews. All available test data from their assessments prior to referral were scrutinized. The boy:girl ratio was 5.5:1. In 22% of the total group a period of regression, including speech and language, had occurred. Epilepsy had been diagnosed in 6% of the children. In 38% of the children there was a definite or highly suspected learning disability/mental retardation according to cognitive test results. About the same proportion had a developmental delay that at the time of assessment could not be definitely classified and in 23% there were clear indications of a normal intellectual function. About 40% of the group exhibited hyperactivity. Differences in expressive vocabulary and adaptive functioning were strongly related to cognitive level. About 20% of the group had AD as the dominating developmental disorder, i.e., they represented a clinical picture of ''classic'' autism. The majority in this group also had learning disability. Another 20%, had ASD combined with a normal intellectual level, some of these conformed to the clinical picture of Asperger syndrome. In a relatively large group (more than half) learning disability or a general developmental delay was as evident as the ASD. In a smaller group (8%) ASD criteria were questionably met. In this group attention deficits in connection with speech and language problems were prominent. The highly individual developmental profiles seen in children with ASDs have to be taken into account when planning intervention and follow-up. The children's medical characteristics also vary considerably and will be detailed in a further report.
Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neur... more Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008-2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband "early intervention" programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autismfriendly environment be "created" around affected individuals.
Acute flaccid myelitis amongst Swedish children with a possible link to an outbreak of enteroviru... more Acute flaccid myelitis amongst Swedish children with a possible link to an outbreak of enterovirus D68 In september 2016 we had several cases of acute flaccid myelitis in our clinic. This coincided with an outbreak of enterovirus D68 (EV-D68) in Sweden during the same period. We describe three cases, of which one tested positive for EV-D68. Acute flaccid paralysis of one or more limbs preceded by an upper respiratory tract infection is highly suspicious of myelitis, and a viral cause must be included in the clinical work-up. In order to detect infection with EV-D68 in suspected acute flaccid myelitis, nasopharyngeal aspirate should be performed as early as possible. EV-D68 is normally not found in stool or cerebrospinal fluid tests but should be included in the clinical work-up. Treatment of acute flaccid myelitis is supportive only. There is no effective antiviral treatment and immunomodulating therapies show little effect. Persisting neurological deficits are common but lethal cas...
Acta paediatrica (Oslo, Norway : 1992), Jan 5, 2016
This study investigated the results from the national, routine 18-month developmental surveillanc... more This study investigated the results from the national, routine 18-month developmental surveillance at Child Healthcare Centres (CHC) on children later diagnosed with autism spectrum disorder (ASD). CHC records of 175 children, diagnosed with ASD before 4.5 years in Stockholm County, Sweden, were reviewed regarding the results of the eight-item neurodevelopmental surveillance. Results were contrasted with normative data from the general child population in Stockholm County. More than one-third of the total ASD group, including half of the group with ASD and intellectual disability (ID), did not pass the required number of items, compared to one in 50 in the general child population. Of those with ASD and ID who had passed, more than one-third experienced developmental regression after 18 months of age. If the CHC surveillance had considered reported regulatory problems - crying, feeding and sleeping - then another 10% of the children with ASD and ID could have been identified during ...
Journal of autism and developmental disorders, Jan 28, 2015
Clinical predictors of 2-year outcome in preschoolers with ASD were studied in a population-based... more Clinical predictors of 2-year outcome in preschoolers with ASD were studied in a population-based group of very young children with ASD (n = 208). Children who gained the most (n = 30) and lost the most (n = 23), i.e., increased or decreased their adaptive functioning outcome according to the Vineland Composite Score between study entry (T1) and follow-up (T2), 2 years later were compared. Individual factors that differed significantly between the two outcome groups were cognitive level, age at referral, not passing expected milestones at 18 months, autistic type behavior problems and regression. However, logistic regression analysis showed that only cognitive level at T1 (dichotomized into IQ < 70 and IQ ≥ 70) made a unique statistically significant contribution to outcome prediction (p = <.001) with an odds ratio of 18.01. The findings have significant clinical implications in terms of information at diagnosis regarding clinical prognosis in ASD.
Autism : the international journal of research and practice, Jan 8, 2014
There is uncertainty about the proportion of children with autism spectrum disorders who do not d... more There is uncertainty about the proportion of children with autism spectrum disorders who do not develop phrase speech during the preschool years. The main purpose of this study was to examine this ratio in a population-based community sample of children. The cohort consisted of 165 children (141 boys, 24 girls) with autism spectrum disorders aged 4-6 years followed longitudinally over 2 years during which time they had received intervention at a specialized autism center. In this study, data collected at the 2-year follow-up were used. Three categories of expressive language were defined: nonverbal, minimally verbal, and phrase speech. Data from the Vineland Adaptive Behavior Scales-II were used to classify expressive language. A secondary objective of the study was to analyze factors that might be linked to verbal ability, namely, child age, cognitive level, autism subtype and severity of core autism symptoms, developmental regression, epilepsy or other medical conditions, and inte...
Early intervention has been reported to improve outcome in children with autism spectrum disorder... more Early intervention has been reported to improve outcome in children with autism spectrum disorders (ASDs). Several studies in the field have been randomized controlled trials (RCTs). The aim of this study was to assess ASD outcome in a large naturalistic study. Two hundred and eight children, aged 20-54 months, with a clinical diagnosis of ASD were given intervention and monitored prospectively in a naturalistic fashion over a period of 2 years. The toddlers were considered representative of all but the most severely multiple disabled preschool children with ASD in Stockholm county. They fell into three cognitive subgroups: one with learning disability, one with developmental delay, and one with normal intellectual functioning. Data on intervention type and intensity were gathered prospectively in a systematic fashion. Intervention was classified into intensive applied behaviour analysis (ABA) and non-intensive, targeted interventions, also based on ABA principles. Children were comprehensively assessed by a research team before the onset of intervention, and then, again, 2 years later. Change in Vineland adaptive behaviour scales composite scores from intake (T1) to leaving the study (T2) was set as the primary outcome variable. The research team remained blind to the type and intensity of interventions provided. One hundred and ninety-eight (95%) of the original samples stayed in the study throughout the whole 2-year period and 192 children had a complete Vineland composite score results both at T1 and T2. Vineland composite scores increased over the 2-year period. This increase was accounted for by the subgroup with normal cognitive functioning. There was no significant difference between the intensive and nonintensive groups. Individual variation was considerable, but no child in the study was ''problem-free'' at follow-up. Our data do not support that children with ASD generally benefit more from the most intensive ABA intervention programs than from less intensive interventions or targeted interventions based on ABA.
Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neur... more Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008-2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband "early intervention" programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autismfriendly environment be "created" around affected individuals.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2013
This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1... more This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β-isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders.
To compare developmental and psychological functioning in two groups of children with autism spec... more To compare developmental and psychological functioning in two groups of children with autism spectrum disorder (asd), one with epilepsy and one without. Sixty 7-17-year-old children in each group were recruited through a range of services in order to screen as representative a sample as possible. Parents were interviewed using the diagnostic interview for social and communication disorders (DISCO-11), and children were clinically examined and their medical histories assessed. The asd and epilepsy (asd+e) group demonstrated a substantially more even gender ratio, with a greater proportion of girls. They were more likely to have received later asd diagnoses and additional medical diagnoses. They also showed more motor difficulties, developmental delays and challenging behaviours, but were no more likely to be aloof and passive. The asd-only group experienced more abnormal fascinations with objects and used brief glances as a means of eye contact more than the asd+e group. Results support important between-group differences with diagnostic and therapeutic implications. asds often present atypically in children with seizures. However, both groups showed widely varying social and linguistic presentations.
Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neur... more Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008-2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband "early intervention" programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autismfriendly environment be "created" around affected individuals.
To compare developmental and psychological functioning in two groups of children with autism spec... more To compare developmental and psychological functioning in two groups of children with autism spectrum disorder (asd), one with epilepsy and one without. Sixty 7-17-year-old children in each group were recruited through a range of services in order to screen as representative a sample as possible. Parents were interviewed using the diagnostic interview for social and communication disorders (DISCO-11), and children were clinically examined and their medical histories assessed. The asd and epilepsy (asd+e) group demonstrated a substantially more even gender ratio, with a greater proportion of girls. They were more likely to have received later asd diagnoses and additional medical diagnoses. They also showed more motor difficulties, developmental delays and challenging behaviours, but were no more likely to be aloof and passive. The asd-only group experienced more abnormal fascinations with objects and used brief glances as a means of eye contact more than the asd+e group. Results support important between-group differences with diagnostic and therapeutic implications. asds often present atypically in children with seizures. However, both groups showed widely varying social and linguistic presentations.
The aim was to explore the frequency of genetic and other medical conditions, including epilepsy,... more The aim was to explore the frequency of genetic and other medical conditions, including epilepsy, in a population-based group of 208 preschool children with early diagnosis of Autism spectrum disorders (ASD) and to relate outcome at a 2-year follow-up to the co-existing medical findings. They had all received early intervention. The Vineland Adaptive Behaviour Scales (VABS-II) composite score served as the primary outcome measure. In the total group, 38/208 children (18 %) had a significant medical or genetic condition. Epilepsy was present in 6.3 % at the first assessment and in 8.6 % at follow-up and was associated with more severe intellectual impairment. A history of regression was reported in 22 %. Children with any medical/genetic condition, including epilepsy, as well as children with a history of regression had significantly lower VABS-II scores at the 2-year follow-up. Children with a medical/genetic condition, including epilepsy, had been diagnosed with ASD at an earlier age than those without such conditions, and early age at diagnosis also correlated negatively with adaptive functioning outcome. The results underscore the importance of considering medical/genetic aspects in all young children with ASD and the requirement to individualize and tailor interventions according to their specific needs.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2010
Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic et... more Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used highresolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first-or second-degree relatives with an ASDrelated neuropsychiatric phenotype in comparison with cases without reported heredity (P ¼ 0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs.
Acta paediatrica (Oslo, Norway : 1992), Jan 6, 2015
Several studies have suggested that rare copy number variants (CNVs) are an important genetic con... more Several studies have suggested that rare copy number variants (CNVs) are an important genetic contributor to autism spectrum disorders. The aims of the study were to use chromosomal microarray to investigate the presence of rare copy number variants in a population-based cohort of well-characterised young children with autism spectrum disorders and to relate the genetic results to neurodevelopmental profiles and medical conditions. We performed chromosomal microarray on samples from 162 children who had been referred to the Stockholm Autism Centre for Young Children in Sweden after being diagnosed with autism spectrum disorder between 20 and 54 months of age. Pathogenic aberrations were detected in 8.6% of the children and variants of uncertain significance were present in another 8.6%. CNVs were more frequent in children with congenital malformations or dysmorphic features as well as in the subgroup with intellectual disability. Our results support the use of chromosomal microarray...
The aim was to characterize the panorama of developmental disorders in 208 preschool children wit... more The aim was to characterize the panorama of developmental disorders in 208 preschool children with a clinical diagnosis of autism spectrum disorder (ASD), referred to a specialized centre, the Autism Centre for Young Children (ACYC), for intervention. At the centre, a research team examined all children according to structured protocols and interviews. All available test data from their assessments prior to referral were scrutinized. The boy:girl ratio was 5.5:1. In 22% of the total group a period of regression, including speech and language, had occurred. Epilepsy had been diagnosed in 6% of the children. In 38% of the children there was a definite or highly suspected learning disability/mental retardation according to cognitive test results. About the same proportion had a developmental delay that at the time of assessment could not be definitely classified and in 23% there were clear indications of a normal intellectual function. About 40% of the group exhibited hyperactivity. Differences in expressive vocabulary and adaptive functioning were strongly related to cognitive level. About 20% of the group had AD as the dominating developmental disorder, i.e., they represented a clinical picture of ''classic'' autism. The majority in this group also had learning disability. Another 20%, had ASD combined with a normal intellectual level, some of these conformed to the clinical picture of Asperger syndrome. In a relatively large group (more than half) learning disability or a general developmental delay was as evident as the ASD. In a smaller group (8%) ASD criteria were questionably met. In this group attention deficits in connection with speech and language problems were prominent. The highly individual developmental profiles seen in children with ASDs have to be taken into account when planning intervention and follow-up. The children's medical characteristics also vary considerably and will be detailed in a further report.
Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neur... more Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008-2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband "early intervention" programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autismfriendly environment be "created" around affected individuals.
Acute flaccid myelitis amongst Swedish children with a possible link to an outbreak of enteroviru... more Acute flaccid myelitis amongst Swedish children with a possible link to an outbreak of enterovirus D68 In september 2016 we had several cases of acute flaccid myelitis in our clinic. This coincided with an outbreak of enterovirus D68 (EV-D68) in Sweden during the same period. We describe three cases, of which one tested positive for EV-D68. Acute flaccid paralysis of one or more limbs preceded by an upper respiratory tract infection is highly suspicious of myelitis, and a viral cause must be included in the clinical work-up. In order to detect infection with EV-D68 in suspected acute flaccid myelitis, nasopharyngeal aspirate should be performed as early as possible. EV-D68 is normally not found in stool or cerebrospinal fluid tests but should be included in the clinical work-up. Treatment of acute flaccid myelitis is supportive only. There is no effective antiviral treatment and immunomodulating therapies show little effect. Persisting neurological deficits are common but lethal cas...
Acta paediatrica (Oslo, Norway : 1992), Jan 5, 2016
This study investigated the results from the national, routine 18-month developmental surveillanc... more This study investigated the results from the national, routine 18-month developmental surveillance at Child Healthcare Centres (CHC) on children later diagnosed with autism spectrum disorder (ASD). CHC records of 175 children, diagnosed with ASD before 4.5 years in Stockholm County, Sweden, were reviewed regarding the results of the eight-item neurodevelopmental surveillance. Results were contrasted with normative data from the general child population in Stockholm County. More than one-third of the total ASD group, including half of the group with ASD and intellectual disability (ID), did not pass the required number of items, compared to one in 50 in the general child population. Of those with ASD and ID who had passed, more than one-third experienced developmental regression after 18 months of age. If the CHC surveillance had considered reported regulatory problems - crying, feeding and sleeping - then another 10% of the children with ASD and ID could have been identified during ...
Journal of autism and developmental disorders, Jan 28, 2015
Clinical predictors of 2-year outcome in preschoolers with ASD were studied in a population-based... more Clinical predictors of 2-year outcome in preschoolers with ASD were studied in a population-based group of very young children with ASD (n = 208). Children who gained the most (n = 30) and lost the most (n = 23), i.e., increased or decreased their adaptive functioning outcome according to the Vineland Composite Score between study entry (T1) and follow-up (T2), 2 years later were compared. Individual factors that differed significantly between the two outcome groups were cognitive level, age at referral, not passing expected milestones at 18 months, autistic type behavior problems and regression. However, logistic regression analysis showed that only cognitive level at T1 (dichotomized into IQ < 70 and IQ ≥ 70) made a unique statistically significant contribution to outcome prediction (p = <.001) with an odds ratio of 18.01. The findings have significant clinical implications in terms of information at diagnosis regarding clinical prognosis in ASD.
Autism : the international journal of research and practice, Jan 8, 2014
There is uncertainty about the proportion of children with autism spectrum disorders who do not d... more There is uncertainty about the proportion of children with autism spectrum disorders who do not develop phrase speech during the preschool years. The main purpose of this study was to examine this ratio in a population-based community sample of children. The cohort consisted of 165 children (141 boys, 24 girls) with autism spectrum disorders aged 4-6 years followed longitudinally over 2 years during which time they had received intervention at a specialized autism center. In this study, data collected at the 2-year follow-up were used. Three categories of expressive language were defined: nonverbal, minimally verbal, and phrase speech. Data from the Vineland Adaptive Behavior Scales-II were used to classify expressive language. A secondary objective of the study was to analyze factors that might be linked to verbal ability, namely, child age, cognitive level, autism subtype and severity of core autism symptoms, developmental regression, epilepsy or other medical conditions, and inte...
Early intervention has been reported to improve outcome in children with autism spectrum disorder... more Early intervention has been reported to improve outcome in children with autism spectrum disorders (ASDs). Several studies in the field have been randomized controlled trials (RCTs). The aim of this study was to assess ASD outcome in a large naturalistic study. Two hundred and eight children, aged 20-54 months, with a clinical diagnosis of ASD were given intervention and monitored prospectively in a naturalistic fashion over a period of 2 years. The toddlers were considered representative of all but the most severely multiple disabled preschool children with ASD in Stockholm county. They fell into three cognitive subgroups: one with learning disability, one with developmental delay, and one with normal intellectual functioning. Data on intervention type and intensity were gathered prospectively in a systematic fashion. Intervention was classified into intensive applied behaviour analysis (ABA) and non-intensive, targeted interventions, also based on ABA principles. Children were comprehensively assessed by a research team before the onset of intervention, and then, again, 2 years later. Change in Vineland adaptive behaviour scales composite scores from intake (T1) to leaving the study (T2) was set as the primary outcome variable. The research team remained blind to the type and intensity of interventions provided. One hundred and ninety-eight (95%) of the original samples stayed in the study throughout the whole 2-year period and 192 children had a complete Vineland composite score results both at T1 and T2. Vineland composite scores increased over the 2-year period. This increase was accounted for by the subgroup with normal cognitive functioning. There was no significant difference between the intensive and nonintensive groups. Individual variation was considerable, but no child in the study was ''problem-free'' at follow-up. Our data do not support that children with ASD generally benefit more from the most intensive ABA intervention programs than from less intensive interventions or targeted interventions based on ABA.
Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neur... more Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008-2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband "early intervention" programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autismfriendly environment be "created" around affected individuals.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2013
This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1... more This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β-isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders.
To compare developmental and psychological functioning in two groups of children with autism spec... more To compare developmental and psychological functioning in two groups of children with autism spectrum disorder (asd), one with epilepsy and one without. Sixty 7-17-year-old children in each group were recruited through a range of services in order to screen as representative a sample as possible. Parents were interviewed using the diagnostic interview for social and communication disorders (DISCO-11), and children were clinically examined and their medical histories assessed. The asd and epilepsy (asd+e) group demonstrated a substantially more even gender ratio, with a greater proportion of girls. They were more likely to have received later asd diagnoses and additional medical diagnoses. They also showed more motor difficulties, developmental delays and challenging behaviours, but were no more likely to be aloof and passive. The asd-only group experienced more abnormal fascinations with objects and used brief glances as a means of eye contact more than the asd+e group. Results support important between-group differences with diagnostic and therapeutic implications. asds often present atypically in children with seizures. However, both groups showed widely varying social and linguistic presentations.
Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neur... more Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008-2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband "early intervention" programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autismfriendly environment be "created" around affected individuals.
To compare developmental and psychological functioning in two groups of children with autism spec... more To compare developmental and psychological functioning in two groups of children with autism spectrum disorder (asd), one with epilepsy and one without. Sixty 7-17-year-old children in each group were recruited through a range of services in order to screen as representative a sample as possible. Parents were interviewed using the diagnostic interview for social and communication disorders (DISCO-11), and children were clinically examined and their medical histories assessed. The asd and epilepsy (asd+e) group demonstrated a substantially more even gender ratio, with a greater proportion of girls. They were more likely to have received later asd diagnoses and additional medical diagnoses. They also showed more motor difficulties, developmental delays and challenging behaviours, but were no more likely to be aloof and passive. The asd-only group experienced more abnormal fascinations with objects and used brief glances as a means of eye contact more than the asd+e group. Results support important between-group differences with diagnostic and therapeutic implications. asds often present atypically in children with seizures. However, both groups showed widely varying social and linguistic presentations.
The aim was to explore the frequency of genetic and other medical conditions, including epilepsy,... more The aim was to explore the frequency of genetic and other medical conditions, including epilepsy, in a population-based group of 208 preschool children with early diagnosis of Autism spectrum disorders (ASD) and to relate outcome at a 2-year follow-up to the co-existing medical findings. They had all received early intervention. The Vineland Adaptive Behaviour Scales (VABS-II) composite score served as the primary outcome measure. In the total group, 38/208 children (18 %) had a significant medical or genetic condition. Epilepsy was present in 6.3 % at the first assessment and in 8.6 % at follow-up and was associated with more severe intellectual impairment. A history of regression was reported in 22 %. Children with any medical/genetic condition, including epilepsy, as well as children with a history of regression had significantly lower VABS-II scores at the 2-year follow-up. Children with a medical/genetic condition, including epilepsy, had been diagnosed with ASD at an earlier age than those without such conditions, and early age at diagnosis also correlated negatively with adaptive functioning outcome. The results underscore the importance of considering medical/genetic aspects in all young children with ASD and the requirement to individualize and tailor interventions according to their specific needs.
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Papers by Mats Eriksson