1. Artuso R, Papa FT, Grillo E, Mucciolo M, Yasui DH, Dunaway KW, Disciglio V, Mencarelli MA, Pollazzon M, Zappella M, Hayek G, Mari F, Renieri A, Lasalle JM, Ariani F. {{Investigation of modifier genes within copy number variations in Rett syndrome}}. {J Hum Genet};2011 (May 19)

MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies.Journal of Human Genetics advance online publication, 19 May 2011; doi:10.1038/jhg.2011.50.

2. Berger BE, Navar-Boggan AM, Omer SB. {{Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination – United States, 2001-2010}}. {BMC Public Health};2011 (May 19);11(1):340.

ABSTRACT: BACKGROUND: Congenital rubella syndrome (CRS) is associated with several negative outcomes, including autism spectrum disorders (ASDs). The objective of this study was to estimate the numbers of CRS and ASD cases prevented by rubella vaccination in the United States from 2001 through 2010. METHODS: Prevention estimates were calculated through simple mathematical modeling, with values of model parameters determined from published literature. Model parameters included pre-vaccine era CRS incidence, vaccine era CRS incidence, the number of live births per year, and the percentage of CRS cases presenting with an ASD. RESULTS: Based on our estimates, 16,600 CRS cases (range: 8300-62,250) were prevented by rubella vaccination from 2001 through 2010 in the United States. An estimated 1228 ASD cases were prevented by rubella vaccination in the United States during this time period. Simulating a slight expansion in ASD diagnostic criteria in recent decades, we estimate that a minimum of 830 ASD cases and a maximum of 6225 ASD cases were prevented. CONCLUSIONS: We estimate that rubella vaccination prevented substantial numbers of CRS and ASD cases in the United States from 2001 through 2010. These findings provide additional incentive to maintain high measles-mumps-rubella (MMR) vaccination coverage.

3. Fehr S, Bebbington A, Nassar N, Downs J, Ronen GM, de Klerk N, Leonard H. {{Trends in the diagnosis of Rett syndrome in Australia}}. {Pediatr Res};2011 (May 16)

Modifications to diagnostic criteria and introduction of genetic testing have likely affected the pattern and timing of Rett syndrome diagnosis. The trends in incidence and prevalence of Rett syndrome in Australia were examined; the cumulative risk of a female being diagnosed determined; and the impact of changes to diagnostic criteria and availability of genetic testing on these frequencies investigated. The population-based Australian Rett Syndrome Database was used to identify a total of 349 verified Rett syndrome females born 1976-2006 and diagnosed 1982-2008. The proportion of female cases born and diagnosed per year and the cumulative risk of a diagnosis were determined. The median age of Rett syndrome diagnosis decreased from 4.5 years if diagnosed before 2000 to 3.5 years if diagnosed after 1999. The cumulative risk of diagnosis had almost doubled by 32 years of age (1/15361 or 6.51 per 100,000 person years (95% CI 5.65-7.39)) in comparison to five years of age (1/8905 or 11.23 per 100,000 person years (95% CI 10.03-12.45)). Earlier age of diagnosis may result in families experiencing less stress and emotional strain compared to those with delayed diagnosis. ABBREVIATIONS::

4. Freedman BH, Kalb LG, Zablotsky B, Stuart EA. {{Relationship Status Among Parents of Children with Autism Spectrum Disorders: A Population-Based Study}}. {J Autism Dev Disord};2011 (May 18)

Despite speculation about an 80% divorce rate among parents of children with an Autism Spectrum Disorder (ASD), very little empirical and no epidemiological research has addressed the issue of separation and divorce among this population. Data for this study was taken from the 2007 National Survey of Children’s Health, a population-based, cross-sectional survey. A total of 77,911 parent interviews were completed on children aged 3-17 years, of which 913 reported an ASD diagnosis. After controlling for relevant covariates, results from multivariate analyses revealed no evidence to suggest that children with ASD are at an increased risk for living in a household not comprised of their two biological or adoptive parents compared to children without ASD in the United States.

5. Kovshoff H, Hastings RP, Remington B. {{Two-Year Outcomes for Children With Autism After the Cessation of Early Intensive Behavioral Intervention}}. {Behav Modif};2011 (May 17)

Evidence from recent meta-analytic and narrative review suggests that early intensive behavioral intervention (EIBI) may improve life chances of preschool children with autism. Unfortunately, there are few data indicating whether early gains are maintained after intervention ceases. The purpose of the present study was to establish the 2-year follow-up outcome for children with autism (N = 41) who had participated in an earlier 2-year controlled comparison of EIBI. Twenty-three children in the intervention group (100% of original sample) and 18 in the treatment-as-usual comparison group (86% of original sample) were located and retested. Group differences favoring intervention substantially diluted in this period but varied significantly between subgroups who had received university-supervised and parent-commissioned interventions, favoring the latter. These groups differed in terms of their baseline characteristics and intensity ofintervention. Results strongly suggesta need for better characterization of those children who would benefit from more active maintenance programs.

6. Naidu S, Johnston MV. {{Neurodevelopmental disorders: Clinical criteria for Rett syndrome}}. {Nat Rev Neurol};2011 (May 17)

7. Roende G, Ravn K, Fuglsang K, Andersen H, Nielsen JB, Brondum-Nielsen K, Jensen JE. {{DXA-measurements in Rett syndrome reveal small bones with low bone mass}}. {J Bone Miner Res};2011 (May 16)

Low bone mass is reported in growth retarded patients harbouring mutations in the X-linked Methyl-CpG-binding protein 2 gene (MECP2) causing Rett syndrome (RTT). We present the first study addressing both bone mineral density (BMD) and bone size in RTT. Our object was to determine whether patients with RTT do have low BMD when correcting for smaller bones by examination with dual-energy X-ray absorptiometry (DXA). We compared areal BMD (aBMD(spine) and aBMD(total hip) ) and volumetric bone mineral apparent density (vBMAD(spine) and vBMAD(neck) ) in 61 patients and 122 matched healthy controls. Further, spine and hip aBMD and vBMAD of patients were associated to clinical risk factors of low BMD, low-energy fractures, MECP2 mutation groups and X chromosome inactivation (XCI). Patients with RTT had reduced bone size in the order of 10%, and showed lower values of spine and hip aBMD and vBMAD (p < 0.001), adjusted for age, pubertal status and body mass index (BMI). aBMD(spine) , vBMAD(spine) and aBMD(total hip) were associated to low-energy fractures (p < 0.05). Walking was significantly associated to aBMD(total hip) and vBMAD(neck,) adjusted for age and BMI. Further, vBMAD(neck) was significantly associated to a diagnosis of epilepsy, anti-epileptic treatment and MECP2 mutation group, but none of the associations to vBMAD(neck) remained clinically significant in a multiple adjusted model including age and BMI. Neither aBMD(spine) , vBMAD(spine) and aBMD(total hip) were significantly associated to epilepsy, anti-epileptic treatment, MECP2 mutation group, XCI and vitamin D status. Low bone mass and small bones are evident in RTT indicating an apparent low bone formation phenotype. (c) 2011 American Society for Bone and Mineral Research.

8. Soke GN, Philofsky A, Diguiseppi C, Lezotte D, Rogers S, Hepburn S. {{Longitudinal changes in Scores on the Autism Diagnostic Interview-Revised (ADI-R) in pre-school children with autism: Implications for diagnostic classification and symptom stability}}. {Autism};2011 (May 17)

We prospectively examined mean changes in Autism Diagnostic Interview-Revised (ADI-R) Total and Domains scores and stability of the ADI-R diagnostic classification in 28 children with autism initially assessed at age 2-4 years and reassessed 2 years later. Mean Total, Social Interaction, and Communication scores decreased significantly from Time 1 to Time 2 Restricted/repetitive Domain mean scores did not change over time. The ADI-R diagnostic classification was stable in 67% of children using the current published criteria. The stability increased to 78% when a modified criterion was used in the Restricted/repetitive Domain and to 88% when the broader ASD criteria were used. Among pre-schoolers with autism, parent-reported symptoms decreased significantly at two-year follow-up in Social and Communication Domains but not in the Restricted/repetitive Domain. However, ADI-R diagnostic classification remained relatively stable over time. Revising ADI-R diagnostic criteria in the Restricted/repetitive Domain or including the broader ASD criteria may improve its sensitivity and diagnostic stability in younger children.