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Purpose We examined associations between vocal communication with canonical syllables and expressive language and then examined 2 potential alternative explanations for such associations. Method Specifically, we tested whether the associations remained when excluding canonical syllables in identifiable words and controlling for the number of communication acts. Participants included 68 preverbal or low verbal children with autism spectrum disorder ( = 35.26 months). Results Vocal communication with canonical syllables and expressive language were concurrently and longitudinally associated with moderate to strong (s = .13-.70) and significant (s < .001) effect sizes. Even when excluding spoken words from the vocal predictor and controlling for the number of communication acts, vocal communication with canonical syllables predicted expressive language. Conclusions The findings provide increased support for measuring vocal communication with canonical syllables and for examining a causal relation between vocal communication with canonical syllables and expressive language in children with ASD who are preverbal or low verbal. In future studies, it may be unnecessary to eliminate identifiable words when measuring vocal communication in this population. Following replication, vocal communication with canonical syllables may be considered when making intervention- planning decisions.

Purpose - Correlates of receptive-expressive vocabulary size discrepancies may provide insights into why language development in children with autism spectrum disorder (ASD) deviates from typical language development and ultimately improve intervention outcomes.
Method - We indexed receptive-expressive vocabulary size discrepancies of 65 initially preverbal children with ASD (20-48 months) to a comparison sample from the MacArthur-Bates Communicative Development Inventories Wordbank (Frank, Braginsky, Yurovsky, & Marchman, 2017) to quantify typicality. We then tested whether attention toward a speaker and oral motor performance predict typicality of the discrepancy 8 months later.
Results - Attention toward a speaker correlated positively with receptive-expressive vocabulary size discrepancy typicality. Imitative and nonimitative oral motor performance were not significant predictors of vocabulary size discrepancy typicality. Secondary analyses indicated that midpoint receptive vocabulary size mediated the association between initial attention toward a speaker and end point receptive-expressive vocabulary size discrepancy typicality.
Conclusions - Findings support the hypothesis that variation in attention toward a speaker might partially explain receptive-expressive vocabulary size discrepancy magnitude in children with ASD. Results are consistent with an input-processing deficit explanation of language impairment in this clinical population. Future studies should test whether attention toward a speaker is malleable and causally related to receptive-expressive discrepancies in children with ASD.

Children's vocal development occurs in the context of reciprocal exchanges with a communication partner who models "speechlike" productions. We propose a new measure of child vocal reciprocity, which we define as the degree to which an adult vocal response increases the probability of an immediately following child vocal response. Vocal reciprocity is likely to be associated with the speechlikeness of vocal communication in young children with autism spectrum disorder (ASD). Two studies were conducted to test the utility of the new measure. The first used simulated vocal samples with randomly sequenced child and adult vocalizations to test the accuracy of the proposed index of child vocal reciprocity. The second was an empirical study of 21 children with ASD who were preverbal or in the early stages of language development. Daylong vocal samples collected in the natural environment were computer analyzed to derive the proposed index of child vocal reciprocity, which was highly stable when derived from two daylong vocal samples and was associated with speechlikeness of vocal communication. This association was significant even when controlling for chance probability of child vocalizations to adult vocal responses, probability of adult vocalizations, or probability of child vocalizations. A valid measure of children's vocal reciprocity might eventually improve our ability to predict which children are on track to develop useful speech and/or are most likely to respond to language intervention. A link to a free, publicly-available software program to derive the new measure of child vocal reciprocity is provided. Autism Res 2018, 11: 903-915. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
LAY SUMMARY - Children and adults often engage in back-and-forth vocal exchanges. The extent to which they do so is believed to support children's early speech and language development. Two studies tested a new measure of child vocal reciprocity using computer-generated and real-life vocal samples of young children with autism collected in natural settings. The results provide initial evidence of accuracy, test-retest reliability, and validity of the new measure of child vocal reciprocity. A sound measure of children's vocal reciprocity might improve our ability to predict which children are on track to develop useful speech and/or are most likely to respond to language intervention. A free, publicly-available software program and manuals are provided.
© 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Theory and research suggest that vocal development predicts "useful speech" in preschoolers with autism spectrum disorder (ASD), but conventional methods for measurement of vocal development are costly and time consuming. This longitudinal correlational study examines the reliability and validity of several automated indices of vocalization development relative to an index derived from human coded, conventional communication samples in a sample of preverbal preschoolers with ASD. Automated indices of vocal development were derived using software that is presently "in development" and/or only available for research purposes and using commercially available Language ENvironment Analysis (LENA) software. Indices of vocal development that could be derived using the software available for research purposes: (a) were highly stable with a single day-long audio recording, (b) predicted future spoken vocabulary to a degree that was nonsignificantly different from the index derived from conventional communication samples, and (c) continued to predict future spoken vocabulary even after controlling for concurrent vocabulary in our sample. The score derived from standard LENA software was similarly stable, but was not significantly correlated with future spoken vocabulary. Findings suggest that automated vocal analysis is a valid and reliable alternative to time intensive and expensive conventional communication samples for measurement of vocal development of preverbal preschoolers with ASD in research and clinical practice. Autism Res 2017, 10: 508-519. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
© 2016 International Society for Autism Research, Wiley Periodicals, Inc.

White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ~70% of young carrier parents who underwent brain MRI. The complex deletion removes the penultimate exon 3 of TM4SF20, a gene encoding a transmembrane protein of unknown function. Minigene analysis showed that the resultant net loss of an exon introduces a premature stop codon, which, in turn, leads to the generation of a stable protein that fails to target to the plasma membrane and accumulates in the cytoplasm. Finally, we report this deletion to be enriched in individuals of Vietnamese Kinh descent, with an allele frequency of about 1%, embedded in an ancestral haplotype. Our data point to a constellation of early language delay and WMH phenotypes, driven by a likely toxic mechanism of TM4SF20 truncation, and highlight the importance of understanding and managing population-specific low-frequency pathogenic alleles.
Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Autism has a strong and complex genetic component, involving several genes. Genomic screens, including our own, have shown suggestive evidence for linkage over a 20-30 cM region on chromosome 2q31-q33. Two subsequent reports showed that the linkage evidence increased in the subset of families with phrase speech delay (PSD), defined as onset of phrase speech later than 3 years of age. To further investigate the linkage in the presumptive candidate region, microsatellite markers in a 2 cM grid covering the interval from 164 to 203 cM were analyzed in 110 multiplex (2 or more sampled autism patients) families. A maximum heterogeneity LOD (HLOD) score of 1.54 was detected at D2S1776 (173 cM) in the overall dataset (dominant model), increasing to 1.71 in the PSD subset. While not conclusive, these data continue to provide suggestive evidence for linkage, particularly considering replication by multiple independent groups. Positive LOD scores extended over the entire region, continuing to define a broad candidate interval. Association studies were performed on several functional candidates mapping within the region. These included GAD1, encoding GAD67, whose levels are reduced in autopsy brain material from autistic subjects, and STK17B, ABI2, CTLA4, CD28, NEUROD1, PDE1A, HOXD1 and DLX2. We found no evidence for significant allelic association between autism and any of these candidates, suggesting that they do not play a major role in the genetics of autism or that substantial allelic heterogeneity at any one of these loci dilutes potential disease-allele association.

BACKGROUND - This study examined whether and how two groups of young adults who were poor readers as children (a relatively compensated group and a group with persistent reading difficulties) differed from nonimpaired readers and if there were any factors distinguishing the compensated from persistently poor readers that might account for their different outcomes.
METHODS - Using functional magnetic resonance imaging, we studied three groups of young adults, ages 18.5-22.5 years, as they read pseudowords and real words: 1) persistently poor readers (PPR; n = 24); 2) accuracy improved (compensated) readers (AIR; n = 19); and 3) nonimpaired readers (NI, n = 27).
RESULTS - Compensated readers, who are accurate but not fluent, demonstrate a relative underactivation in posterior neural systems for reading located in left parietotemporal and occipitotemporal regions. Persistently poor readers, who are both not fluent and less accurate, activate posterior reading systems but engage them differently from nonimpaired readers, appearing to rely more on memory-based rather than analytic word identification strategies.
CONCLUSIONS - These findings of divergent neural outcomes as young adults are both new and unexpected and suggest a neural basis for reading outcomes of compensation and persistence in adults with childhood dyslexia.

Using quantitative magnetic resonance imaging morphometry, we report that the whole brain volumes of patients with neurofibromatosis-1 are significantly larger than normal, confirm the prevalence of macrocephaly as about 50%, and report that macrocephaly in patients with neurofibromatosis-1 does not appear to be related to the familial or sporadic origin of the neurofibromatosis-1 or to the presence or absence of T2-weighted hyperintensities. No strong relationship emerged between the extent of neurofibromatosis-1-associated impairment of cognitive functions and degree of macrocephaly; however, the macrocephalic neurofibromatosis-1 group did have a significant verbal impairment relative to the nonmacrocephalic neurofibromatosis-1 group in vocabulary (P < .009).

Complex segregation analysis was performed on pedigrees ascertained through 45 probands (26 males, 19 females) with a history of preschool speech and language disorders. Hypotheses concerning mode of inheritance were tested using the POINTER segregation analysis program. Although there is strong evidence for familial transmission of this trait, we were unable to distinguish between a major gene and multifactorial transmission model using likelihood-ratio chi-square tests. Future studies with quantitative measures of speech and language disorders are needed to resolve the issue of mode of inheritance for this trait.