Podcast: A 4th of July quickie on new data for treatment of autism symptoms
Background: Phelan-McDermid syndrome (PMS) occurs as a result of a chromosomal abnormality, most frequently
deletion, in the long arm of chromosome 22, involving the SHANK3 gene. Our goal was to prospectively assess the
neurological phenotype in this syndrome.
METHODS: Twenty-nine participants were recruited from ongoing studies in PMS at the Seaver Autism Center. They
had a structured, uniform neurological examination performed by a pediatric neurologist (Y.F.). Abnormal findings
were graded as mild, moderate or severe. In addition, reports of seizures, magnetic resonance imaging (MRI) and
electroencephalograms (EEG) were reviewed. We calculated the frequency and severity of neurological
abnormalities, as well as correlations between items on the neurological examination and items on the Mullen Scales
of Early Learning and on the Vineland Adaptive Behavioral Scales (VABS).
RESULTS: Hypotonia, abnormal gait, fine motor coordination deficits, and expressive and receptive language delays
were present in all participants. Attention deficits were present in 96% (severe in 62%), and abnormal visual tracking
was present in 86%. A history of seizures was obtained in 44.8% of participants but 46.1% of these were febrile only.
Of the 13 EEG reports available for review – 69.2% were abnormal- with epileptic features present in 53.8%.
Abnormalities were present in 62.5% of MRI reports. Correlations were found between neurological abnormalities
and scores on the Mullen and Vineland Scales.
CONCLUSIONS: Neurological abnormalities are very common in PMS and are correlated with measures of cognitive
and adaptive functioning. The neurological examination may be used for clinical diagnosis, identification of PMS
phenotypes, and, in the future, for evaluation of therapy.
Background: We examined racial/ethnic disparities in school-based behavioral health service use for children with psychiatric disorders.
Methods: Medicaid claims data were used to compare the behavioral healthcare service use of 23,601 children aged 5-17 years by psychiatric disorder (autism, attention deficit hyperactivity disorder [ADHD], conduct/oppositional defiant disorder, and “other”) and by race/ethnicity (African-American, Hispanic, white, and other). Logistic and generalized linear regression analyses were used.
Results: Differences in service use by racial/ethnic group were identified within and across diagnostic groups, both for in-school service use and out-of-school service use. For all disorders, Hispanic children had significantly lower use of in-school services than white children. Among children with ADHD, African-American children were less likely to receive in-school services than white children; however, there were no differences in adjusted annual mean Medicaid expenditures for in-school services by race/ethnicity or psychiatric disorders. Statistically significant differences by race/ethnicity were found for out-of-school service use for children with ADHD and other psychiatric disorders. There were significant differences by race/ethnicity in out-of-school service use for each diagnostic group.
Conclusions: Differences in the use of school-based behavioral health services by racial and ethnic groups suggest the need for culturally appropriate outreach and tailoring of services to improve service utilization.
Keywords: Medicaid; behavioral health; health disparity; mental health; school-based health services.
Whole-exome and whole-genome sequencing have facilitated the large-scale discovery of de novo variants in human disease. To date, most de novo discovery through next-generation sequencing focused on congenital heart disease and neurodevelopmental disorders (NDDs). Currently, de novo variants are one of the most significant risk factors for NDDs with a substantial overlap of genes involved in more than one NDD. To facilitate better usage of published data, provide standardization of annotation, and improve accessibility, we created denovo-db (http://denovo-db.gs.washington.edu), a database for human de novo variants. As of July 2016, denovo-db contained 40 different studies and 32,991 de novo variants from 23,098 trios. Database features include basic variant information (chromosome location, change, type); detailed annotation at the transcript and protein levels; severity scores; frequency; validation status; and, most importantly, the phenotype of the individual with the variant. We included a feature on our browsable website to download any query result, including a downloadable file of the full database with additional variant details. denovo-db provides necessary information for researchers to compare their data to other individuals with the same phenotype and also to controls allowing for a better understanding of the biology of de novo variants and their contribution to disease.