Marijcke W. M. Veltman

Three Decades of Child Maltreatment Research: Implications for the School Years

Research studies over the years have attempted to demonstrate and highlight developmental delay in maltreated children. These delays could contribute to a lower readiness for school. This literature review investigates whether infants and primary school-age children with a history of maltreatment really have been shown to struggle at school due to specific developmental delay. The extent of maltreatment, definition problems, and parenting styles are discussed and the results of a systematic review of empirical studies presented. The majority of the studies cited in this review indicate that child abuse is related to delayed language, cognitive development, low IQ, and poor school performance in some way.

Autism spectrum disorders in Prader-Willi and Angelman syndromes: a systematic review.

Autism spectrum disorders (ASDs) have been linked with maternally derived duplications/triplications of chromosome 15q11–13 and therefore might occur more frequently in people with Prader–Willi syndrome (PWS) when due to uniparental disomy (UPD), than in other forms of chromosomal abnormality involving this region [i.e. deletion (DEL) forms of PWS and DEL+UPD forms of Angelmans syndrome –(AS)]. Twelve studies regarding ASD in PWS and AS were reviewed. It was noteworthy that among the genetically confirmed UPD and DEL cases of PWS and AS, the rate of ASD was 25.3% (38/150; range 0–36.5%) in PWS and 1.9% in AS (2/104; range 0–100%) (Fishers exact P<0.0001). Among the subset of cases with confirmed UPD or DEL, the rate of ASD in the UPD cases of PWS was significantly higher (20/53) than in the remaining combined samples (i.e. DEL PWS+UPD AS+DEL AS cases; 20/201) (Fishers exact P<0.0001). ASD in UPD PWS cases (20/53) compared with DEL PWS cases (18/97) was also statistically significant (Fishers exact P=0.0176). Thus, the limited available evidence supported the prediction that overexpression of maternally imprinted genes in 15q11–13 confers a risk for ASD. Further research will be required to confirm these findings.

Chromosome 15q11-13 abnormalities and other medical conditions in individuals with autism spectrum disorders.

Objectives The frequency of abnormalities of 15q11-q13 and other possibly causal medical disorders including karyotypic abnormalities was investigated in an unselected series of children who were referred to one of two autism assessment centres. Methods Two hundred and twenty-one cases were assessed using the Autism Diagnostic Interview and Observation Schedule and, where appropriate, standardized tests of intelligence and language abilities. Medical histories and notes were reviewed, and molecular and cytogenetic investigations used to detect chromosomal abnormalities. Results One hundred and eighty-one cases were diagnosed according to International Classification of Diseases – version 10 criteria as having an autism spectrum disorder (autistic-like Pervasive Developmental Disorder) and 40 cases as having other disorders. Twenty-one (11.6%) of the children with autism spectrum disorders had a possibly causal condition compared with six (15%) of the children with other diagnoses. One child with an autism spectrum disorder had a paternally inherited familial duplication of 15q11-13. The pattern of genotype–phenotype correlation within the family indicated that this form of abnormality might carry a risk for developmental difficulties, although the risk did not appear to be specific for autism spectrum disorders. Conclusion The overall rate of possibly causal medical and cytogenetic conditions in children with autism spectrum disorders was low and no different from the rate of disorder in children with other developmental/neuropsychiatric disorders that attended the same clinics. Further research is required to determine whether paternal duplication of 15q11-13 gives rise to adverse developmental outcomes.

Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13

We present clinical data on 33 subjects with additional copies of the Prader‐Willi‐Angelman critical region (PWACR) contained in a supernumerary marker chromosome (SMC). Twenty‐three subjects had a typical large non‐mosaic SMC(15) containing two copies of the PWACR. They showed a variable but generally severe phenotype of learning disability and autism, with seizures in approximately two‐thirds. The other 10 differed from this typical pattern in respect of mosaicism, variation in copy number, or arrangement of the PWACR within the SMC or number of SMC per cell. Clinical severity increased with the number of additional copies of the PWACR and decreased with mosaicism for a normal cell line. There was a trend for a larger number of seizures to be associated with more severe learning disability. Three subjects with interstitial triplications of 15q11‐q13 showed a range of phenotypes similar to those of the typical large SMC(15). All additional copies of the PWACR in this series were maternally‐derived. FISH and molecular data localizing the breakpoints of the rearrangements have been previously published or are included in this report. No correlations were found between specific clinical features and variations in breakpoints proximal and distal to the PWACR.

An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum disorder

Autism (OMIM 209850) is a neurodevelopmental disorder with a significant genetic component of a complex nature. Cytogenetic abnormalities in the Prader–Willi/Angelman syndrome critical region (PWACR) on chromosome 15 (q11‐13) have been described in several individuals with autism. We have examined five microsatellite markers spread across the 4 Mb PWACR for linkage disequilibrium (LD) in 148 families with autism spectrum disorder (ASD) and a subset of 82 families with autism using the extended transmission disequilibrium test (ETDT). The markers examined were D15S11, D15S128, D15S1506, GABRB3, and D15S1002. In addition we have examined the microsatellite D15S822 for hemizygous deletion status in our sample as it had been previously reported to be increased in autism. We found no significant LD with any of the markers tested either in the ASD or autism families when looking at paternal and maternal meioses combined. However, as there are known imprinted genes in the region, including possibly GABRB3, we also examined for LD in paternal and maternal meioses separately. Examining paternal transmissions only, we found marginal evidence for LD with a protective allele at marker D15S11 in the ASD families (Chi‐sq 7 df, P = 0.05) and marginal evidence for risk alleles at markers D15S1506 (Chi‐sq 13.7, 6 df, P = 0.06), GABRB3 (Chi‐sq 15.9, 8 df, P = 0.11) and D15S1002 (Chi‐sq 17.7, 9 df, P = 0.08) in the autism only families. The allele responsible for the association with GABRB3 is the 191 allele which was previously reported to be overtransmitted. Hemizygous deletion of the microsatellite D15S822 was found in 3 out of 340 independent chromosomes in our sample; a rate of 0.8%. This is not significantly different to the frequency in the general population. In conclusion, our results did not rule out the involvement of this chromosomal region, but provided further evidence, albeit very limited, to implicate GABRB3. Further more systematic work in larger samples is required and confirmation that GABRB3 is imprinted is desirable.

Pictures in the classroom: can teachers and mental health professionals identify maltreated children's drawings?

The aim of this paper is to investigate whether teachers and mental health professionals are able to identify drawings produced by maltreated children, at a level greater than chance, when these drawings are presented to them at the same time as drawings created by non-maltreated matched control children. In a relatively small study, a group of 33 mental health practitioners (MHPs) and a group of 10 teachers were shown sets of drawings and asked whether they could identify the maltreated childrens drawings. It was found that there was no significant difference between mental health practitioner and teacher groups in identifying child maltreatment from Favourite Kind of Day Drawings (FKDs) (Manning, 1987) and Kinetic Family Drawings (KFD) (Burns and Kaufman, 1970). The results also point to the KFD as a more reliable drawing technique, but only when it is known that maltreatment is definitely present, and in a situation with no a priori knowledge it should not be used for the identification of maltreatment. Copyright

An association analysis of GABRB3, a candidate gene of the GABAA receptor complex on chromosome 15Q and autism spectrum disorder. [In Special Issue: XIII World Congress of Psychiatric Genetics 2005]

Cathy Barr, Tim Crow, Lynn DeLisi, Richard Ebstein, James Hudziak, Hai‐Gwo Hwu, Florence Levy, Michael Lyons, Michael Owen, Carlos Pato, Michele Pato, David Pauls, Leena Peltonen, Anita Thapar, Richard Todd, Christine Van Broeckhoven, Yufeng Wang, and Hiroshi Yoneda

Chromosome 15 abnormalities and autistic symptomatology: case - control investigations

Cathy Barr, Tim Crow, Lynn DeLisi, Richard Ebstein, James Hudziak, Hai‐Gwo Hwu, Florence Levy, Michael Lyons, Michael Owen, Carlos Pato, Michele Pato, David Pauls, Leena Peltonen, Anita Thapar, Richard Todd, Christine Van Broeckhoven, Yufeng Wang, and Hiroshi Yoneda