Acoustic Analyses of Tone Productions in Sequencing Contexts Among Cantonese-Speaking Preschool Children With and Without Childhood Apraxia of Speech.

PURPOSE: Pitch variations (tone productions) have been reported as a measure to differentiate Cantonese-speaking children with and without childhood apraxia of speech (CAS). This study aims to examine fundamental frequency (F0) changes within syllables and the effects of syllable structure, lexical status, and syllable positions on F0 in Cantonese-speaking preschool children with and without CAS. METHOD: Six children with CAS, six children with non-CAS speech sound disorder plus language disorder (S&LD), 22 children with speech sound disorder only (SSD), and 63 children with typical speech-language development (TD) performed the tone sequencing task (TST). Growth curve analysis was employed to analyze and compare the F0 values within syllables with three Cantonese tones (high level, high rising, and low falling). The analysis considered the effects of syllable structure (vowel and consonant-vowel), lexical status (word and nonword), and syllable position (initial, medial, and final) on F0, as well as comparisons within and between groups. RESULTS: Within each group, the effects of syllable structure and position on F0 values were found with different patterns. Between-group comparisons showed that the CAS group had reduced F0 contrasts. The CAS group could be differentiated from the control groups based on interactions of F0 with syllable structure and position, but not lexical status. The dissimilarity of F0 values detected between the CAS and SSD/TD groups was more prominent than that observed between the CAS and S&LD groups. CONCLUSIONS: This study demonstrated that Cantonese-speaking children with CAS had difficulty in varying F0 within syllables as compared to those without CAS, suggesting pitch variation difficulty and language-specific impairment profiles in CAS. Future investigations of objective measures for identifying Cantonese speakers with CAS and cross-linguistic investigations using growth curve analysis and the TST are suggested.

Speech Elicitation Methods for Measuring Articulatory Control.

PURPOSE: Spatiotemporal index (STI) is a common measure of articulatory variability used to examine speech-motor control. However, the methods used to elicit productions for measuring STI have varied across studies. The aim of this study was to determine whether STI values are affected by changes in elicitation methods. METHOD: Lip aperture STI (LA STI) was calculated for 19 monolingual English-speaking young adults based upon the production of four declarative sentences that varied by length and complexity. Using a 2 × 2 design, productions were elicited under the following two conditions: repetition type (consecutive vs. pseudorandom) and stimulus presentation type (auditory vs. combined auditory and visual). Conditions for eliciting productions were counterbalanced among participants. RESULTS: There was a main effect of repetition type (p < .001) and sentence type (p < .030). Pseudorandom repetitions resulted in higher mean LA STI values across sentence types compared to those computed from consecutive repetitions. There were no significant differences for stimulus presentation type. That is, no differences in mean LA STI were found between the auditory versus combined auditory and visual presentations. CONCLUSIONS: Our findings show that the methods used to elicit sentence productions have a significant effect on LA STI values. Findings suggest that there is a need for researchers to consider these effects when designing methods for measuring LA STI.

DNA methylation profiles in individuals with rare, atypical 7q11.23 CNVs correlate with GTF2I and GTF2IRD1 copy number.

Williams-Beuren syndrome (WBS) and 7q11.23 duplication syndrome (Dup7) are rare neurodevelopmental disorders caused by deletion and duplication of a 1.5 Mb region that includes at least five genes with a known role in epigenetic regulation. We have shown that CNV of this chromosome segment causes dose-dependent, genome-wide changes in DNA methylation, but the specific genes driving these changes are unknown. We measured genome-wide whole blood DNA methylation in six participants with atypical CNV of 7q11.23 (three with deletions and three with duplications) using the Illumina HumanMethylation450k array and compared their profiles with those from groups of individuals with classic WBS or classic Dup7 and with typically developing (TD) controls. Across the top 1000 most variable positions we found that only the atypical rearrangements that changed the copy number of GTF2IRD1 and/or GTF2I (coding for the TFII-IRD1 and TFII-I proteins) clustered with their respective syndromic cohorts. This finding was supported by results from hierarchical clustering across a selection of differentially methylated CpGs, in addition to pyrosequencing validation. These findings suggest that CNV of the GTF2I genes at the telomeric end of the 7q11.23 interval is a key contributor to the large changes in DNA methylation that are seen in blood DNA from our WBS and Dup7 cohorts, compared to TD controls. Our findings suggest that members of the TFII-I protein family are involved in epigenetic processes that alter DNA methylation on a genome-wide level.

Relations Between Selective Mutism and Speech Sound Disorder in Children With 7q11.23 Duplication Syndrome.

PURPOSE: The aim of this study was to explore relations between speech sound disorder severity and selective mutism in a group of children with 7q11.23 duplication syndrome (Dup7), a genetic condition predisposing children to childhood apraxia of speech (CAS) and other speech sound disorders and to anxiety disorders, including selective mutism and social anxiety disorder. METHOD: Forty-nine children aged 4-17 years with genetically confirmed Dup7 completed the Goldman-Fristoe Test of Articulation-Second Edition (GFTA-2), the Expressive Vocabulary Test-Second Edition (EVT-2), and the Differential Ability Scales-Second Edition (DAS-II). Parents completed the Anxiety Disorders Interview Schedule-Parent (ADIS-P). RESULTS: Mean standard scores (SSs) were 65.67 for the GFTA-2, 92.73 for the EVT-2, and 82.69 for the DAS-II General Conceptual Ability (GCA; similar to IQ). Standard deviations for all measures were larger than for the general population. GFTA-2 SS was significantly correlated with both EVT-2 SS and DAS-II GCA. Based on the ADIS-P, 22 participants (45%) were diagnosed with selective mutism and 29 (59%) were diagnosed with social anxiety disorder. No significant differences in performance on any of the measures were found either between the group with a selective mutism diagnosis and the group that did not have selective mutism or between the group with a selective mutism and/or social anxiety disorder diagnosis and the group that did not have either disorder. CONCLUSIONS: For children with Dup7, neither the diagnosis of selective mutism nor the diagnosis of selective mutism and/or social anxiety disorder was related to severity of speech sound disorder, expressive vocabulary ability, or overall intellectual ability. Accordingly, treatment for speech sound disorder alone is unlikely to lead to remission of selective mutism or social anxiety disorder. Instead, selective mutism and/or social anxiety disorder should be treated directly. Further research is needed to determine if these findings generalize to other populations, such as children with idiopathic CAS.

The Reliability of Expert Diagnosis of Childhood Apraxia of Speech.

PURPOSE: The current standard for clinical diagnosis of childhood apraxia of speech (CAS) is expert clinician judgment. The psychometric properties of this standard are not well understood; however, they are important for improving clinical diagnosis. The purpose of this study is to determine the extent to which experts agree on the clinical diagnosis of CAS using two cohorts of children with mixed speech sound disorders (SSDs). METHOD: Speech samples of children with SSDs were obtained from previous and ongoing research from video recordings of children aged 3-8 years (n = 36) and audio recordings of children aged 8-17 years (n = 56). A total of 23 expert, English-speaking clinicians were recruited internationally. Three of these experts rated each speech sample to provide a description of the observed features and a diagnosis. Intrarater reliability was acceptable at 85% agreement. RESULTS: Interrater reliability on the presence or absence of CAS among experts was poor both as a categorical diagnosis (κ = .187, 95% confidence interval [CI] [0.089, 0.286]) and on a continuous "likelihood of CAS" scale (0-100; intraclass correlation = .183, 95% CI [.037, .347]). Reliability was similar across the video-recorded and audio-only samples. There was greater agreement on other diagnoses (such as articulation disorder) than on the diagnosis of CAS, although these too did not meet the predetermined standard. Likelihood of CAS was greater in children who presented with more American Speech-Language-Hearing Association CAS consensus features. CONCLUSIONS: Different expert raters had different thresholds for applying the diagnosis of CAS. If expert clinician judgment is to be used for diagnosis of CAS or other SSDs, further standardization and calibration is needed to increase interrater reliability. Diagnosis may require operationalized checklists or reliable measures that operate along a diagnostic continuum. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23949105.

Update on Identification and Treatment of Infants and Toddlers With Suspected Childhood Apraxia of Speech.

PURPOSE: The purpose of this tutorial is to (a) provide an updated review of the literature pertaining to proposed early features of childhood apraxia of speech (CAS), (b) discuss the findings of recent treatment studies of infants and toddlers with suspected CAS (sCAS), and (c) present evidence-based strategies and tools that can be used for the identification of and intervention for infants and toddlers with sCAS or at high risk for the disorder. METHOD: Since Davis and Velleman's (2000) seminal work on assessment and intervention in infants and toddlers with sCAS, limited research has guided clinicians in the complex task of identifying and treating early speech motor difficulties prior to a definitive diagnosis of CAS. Following the structure of Davis and Velleman, we explore the proposed early characteristics of CAS with reference to contemporary research. Next, we describe the limited treatment studies that have investigated intervention for infants and toddlers at risk of or suspected of having CAS. Finally, we present practical suggestions for integrating this knowledge into clinical practice. CONCLUSIONS: Many of the originally proposed correlates of CAS in infants and toddlers now have research supporting their presence. However, questions remain about the developmental trajectory of the disorder. Although limited in number and restricted by lack of experimental control, emerging treatment studies can help guide clinicians in providing appropriate intervention to infants and toddlers with sCAS who need not wait for a definitive diagnosis to initiate intervention.

Dose frequency randomized controlled trial for Dynamic Temporal and Tactile Cueing (DTTC) treatment for childhood apraxia of speech: protocol paper.

BACKGROUND: Childhood apraxia of speech (CAS) is a pediatric motor-based speech sound disorder that requires a specialized approach to intervention. The extant literature on the treatment of CAS commonly recommends intensive treatment using a motor-based approach, with some of the best evidence supporting the use of Dynamic Temporal and Tactile Cueing (DTTC). To date, a rigorous and systematic comparison of high and low dose frequency (i.e., frequency of therapy sessions) has not been undertaken for DTTC, resulting in a lack of evidence to guide decisions about the optimal treatment schedule for this intervention. The current study aims to fill this gap in knowledge by comparing treatment outcomes when dose frequency is varied. METHODS: A randomized controlled trial will be conducted to examine the efficacy of low versus high dose frequency on DTTC treatment outcomes in children with CAS. A target of 60 children, 2;6-7;11 years of age, will be recruited to participate in this study. Treatment will be provided in the community setting by speech-language pathologists who have completed specialized training administering DTTC in a research reliable manner. True randomization with concealed allocation will be used to assign children to either the low or high dose frequency group. Treatment will be administered in 1-h sessions either 4 times per week over a 6-week period (high dose) or 2 times per week over a 12-week period (low dose). To measure treatment gains, probe data will be collected before treatment, during treatment, and 1 day, 1 week, 4 weeks, and 12 weeks post-treatment. Probe data will consist of customized treated words and a standard set of untreated words to assess generalization of treatment gains. The primary outcome variable will be whole word accuracy, encompassing segmental, phonotactic, and suprasegmental accuracy. DISCUSSION: This will be the first randomized controlled trial to evaluate dose frequency for DTTC treatment in children with CAS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05675306, January 6, 2023.

Clinical practice of childhood apraxia of speech in Hong Kong: A web-based survey study.

BACKGROUND: A survey study on clinical practice not only provides insight into the implementation of knowledge, but also informs future investigations. There is a limited understanding of childhood apraxia of speech (CAS) in Cantonese speakers. This study examined the clinical practice of CAS in Hong Kong and discussed future directions of research for better evidence-based practice. METHODS: Qualified Hong Kong pediatric speech-language pathologists (SLPs) completed the online questionnaire, which had a total of 48 questions regarding their knowledge of and experience with CAS in Cantonese speakers, including assessment, diagnosis, and treatment. RESULTS: Seventy-seven responses were received from Hong Kong SLPs. Most of the SLPs (83.2%) rated their understanding of CAS as either "a little" or "fair". About half (53.2%) of the respondents had worked with children with CAS. No standardized assessment or objective/quantitative measures were used clinically. Instead, seven assessment tasks, including imitation of polysyllabic words and speech and language samples were used commonly. Perceptual judgment of clinical features is still the most popular approach for diagnosis, with a variety of lists in use. Of concern was that, in addition to using some evidence-based approaches, local SLPs treated CAS using approaches that have limited evidence, in the context of less treatment frequency, targeting both speech and language skills within the same session, and with only partial implementation of the approaches. CONCLUSIONS: The results suggest that the understanding of CAS among local SLPs requires attention. One reason for this is that evidence regarding the assessment, diagnosis, and treatment of Cantonese speakers with CAS is still limited. Future investigations are needed.

Assessment and Diagnostic Standards of Apraxia of Speech in Chinese-Speaking Adults and Children: A Scoping Review.

PURPOSE: Apraxia of speech (AOS) and childhood apraxia of speech (CAS) are motor-based speech disorders that have been well studied in Indo-European languages. There is limited understanding of these disorders in speakers of Sino-Tibetan languages, such as Chinese. The purpose of this study is to review methods used in research studies for the assessment and diagnosis of AOS and CAS in Chinese speakers. METHOD: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. Articles with a focus on AOS or CAS in Chinese speakers were systematically searched in seven English and six Chinese databases. Three reviewers performed independent screening, data extraction, and quality assessment after obtaining 100% agreement on the prescreening exercise. A qualitative analysis was conducted to rate the quality of diagnoses, ranging from high (Level I) to low (Level III), with Level IV assigned to studies for which the appropriate rating was unclear due to insufficient evidence. RESULTS: Twenty-eight AOS articles and five CAS articles were identified. A variety of assessment and diagnostic methods were reported. No study of Chinese speakers with AOS or CAS received a rating of Level I. The highest level achieved was Level IIIa for both AOS and CAS studies. CONCLUSIONS: There is no reliable and valid test or method for the diagnosis of AOS or CAS in Chinese speakers. The current gold standard of diagnosis is based upon expert perceptual judgment. Further single-language and cross-linguistic investigations of AOS and CAS and the future development of assessment and diagnostic methods are recommended.

Lexical tone perception and production in Cantonese-speaking children with childhood apraxia of speech: a pilot study.

Childhood apraxia of speech (CAS) is a paediatric motor speech disorder. We investigated the lexical tone perception and production abilities of children with CAS and the relationships between the two. Three children with CAS, aged between 3;7 and 5;8, were given the Cantonese Tone Identification Test (CANTIT) and the Hong Kong Cantonese Articulation Test (HKCAT) for assessment of tone perception and production, respectively. Accuracy and error patterns were investigated based on their performance on the two tests. Correlation analysis was performed on children's perception and production scores. Two children scored at the lowest rank on the CANTIT, while one child obtained a Z score of 0. All children scored three standard deviations below the mean on the HKCAT. No statistical differences were found among the six tones with respect to perception accuracy, H(5) = 3.731, p = 0.589. Error analysis showed that children with CAS demonstrated more confusion on perceiving tones compared with TD peers. There were no main effects for task (F(1,2) = 0.040, p = 0.859) or tone (F(5,10 = 0.997, p = 0.467); nor were there task or tone interaction effects on perception versus production accuracy (F(5,10) = 1.772, p = 0.206). Tone perception and production accuracy were not significantly correlated (r2 = 0.181, p = 0.078). Tone perception deficits were evident in two out of three children with CAS, while all children had lexical tone production difficulties. In this small sample, tone production was more universally affected than tone perception.

Early diagnostic indicators of childhood apraxia of speech in young children with 7q11.23 duplication syndrome: preliminary findings.

Limited evidence for early indicators of childhood apraxia of speech (CAS) precludes reliable diagnosis before 36 months, although a few prior studies have identified several potential early indicators. We examined these possible early indicators in 10 toddlers aged 14-24 months at risk for CAS due to a genetic condition: 7q11.23 duplication syndrome (Dup7). Phon Vocalisation analyses were conducted on phonetic transcriptions of each child's vocalisations during an audio-video recorded 30-minute play session with a caregiver and/or a trained research assistant. The resulting data were compared to data previously collected by Overby from similar-aged toddlers developing typically (TD), later diagnosed with CAS (LCAS), or later diagnosed with another speech sound disorder (LSSD). The Dup7 group did not differ significantly from the LCAS group on any measure. In contrast, the Dup7 group evidenced significant delays relative to the LSSD group on canonical babble frequency, volubility, consonant place diversity, and consonant manner diversity and relative to the TD group not only on these measures but also on canonical babble ratio, consonant diversity, and vocalisation structure diversity. Toddlers with Dup7 also demonstrated expressive vocabulary delay as measured by both number of word types orally produced during the play sessions and primary caregivers' responses on a standardised parent-report measure of early expressive vocabulary. Examining babble, phonetic, and phonotactic characteristics from the productions of young children may allow for earlier identification of CAS and a better understanding of the nature of CAS.

The Use of Segmental and Suprasegmental Sequencing Skills to Differentiate Children With and Without Childhood Apraxia of Speech: Protocol for a Comparative Accuracy Study.

BACKGROUND: Childhood apraxia of speech (CAS) is a motor-based speech sound disorder (SSD) with a core impairment in the planning and programming of spatiotemporal parameters of speech movement sequences. CAS may cause deficits in both segmental and suprasegmental components of speech, and it can severely affect children's ability to speak intelligibly and communicate effectively and impact their quality of life. Assessment tasks, such as the maximum performance tasks (MPT) and Syllable Repetition Task (SRT), examine children's segmental sequencing skills to assist with the diagnosis of CAS. In Hong Kong, although the MPT and SRT have been used clinically to diagnose CAS in Cantonese-speaking children, their validity has not been reported. There is an urgent need for such investigations. Suprasegmentally, lexical stress errors have been reported as a consensual feature and to aid in the diagnosis of CAS. However, there are challenges in diagnosing CAS in children who speak tonal languages like Cantonese. A recent study has reported lexical tone errors in Cantonese-speaking children with CAS. Furthermore, deficits in pitch-variation skills were found in Cantonese-speaking children with CAS using a tone sequencing task (TST). It is hypothesized that there is a universal deficit in pitch-variation skills among tonal and nontonal language speakers with CAS. Further investigations of pitch-variation skills using the TST in Cantonese-speaking children with CAS may shed light on suprasegmental deficits in tonal languages and contribute to the development of a valid diagnostic tool for CAS in children who speak other tonal languages, such as Vietnamese, Thai, and Mandarin. OBJECTIVE: This study aims to examine the diagnostic potential of the MPT, SRT, and TST in diagnosing Cantonese-speaking children with CAS and to investigate pitch-variation skills in Cantonese-speaking children with and without CAS. METHODS: A total of 25 children with CAS and 3 groups of age- and gender-matched controls (non-CAS SSD only group, non-CAS SSD co-occurring with language impairment group, and typical development group) will be recruited. All participants will perform the MPT, SRT, and TST measures. Their performances on these tools will be perceptually judged and acoustically measured. RESULTS: Data collection will last from January 1, 2022, to October 30, 2023. As of August 2022, the project has recruited 4 children in the CAS group, 21 children in the non-CAS SSD group, 4 children in the speech and language impairment group, and 53 children in the typical development group. CONCLUSIONS: It is anticipated that Cantonese-speaking children with CAS will have poorer pitch-variation skills than the control groups and that the MPT, SRT, and TST will be appropriate diagnostic tools for identifying CAS in Cantonese-speaking children. The project will benefit the field of speech-language pathology locally and internationally, with short- and long-term impacts. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40465.

Pitch Variation in Children With Childhood Apraxia of Speech: Preliminary Findings.

Introduction Pitch variation, which refers to one's ability to vary fundamental frequency (F0) within or between syllables when speaking, has not been investigated in children with childhood apraxia of speech (CAS). However, pitch variation plays an important role in tone languages, as varying F0 patterns communicate different lexical meanings. This study investigated pitch variation abilities in individuals with CAS via the tone-sequencing tasks (TSTs), focusing on task performance and the effects of syllable structure, lexical status, and tones. Method Three Cantonese-speaking children with CAS (aged 3;7-5;8 [years;months]) and six children without CAS participated in the study. Children without CAS were divided into two control groups, comprising those with speech and/or language impairment or typical development. TSTs consisted of 56 sets of five repetitions of stimuli. The stimuli varied in syllable structure, lexical status, and tones. Percentage of tones correct (PTC), consistency scores, F0 values, and acoustic repetition duration were measured. Results The CAS group performed more poorly than the control groups on the TST with respect to tone accuracy, consistency, and repetition duration. No interaction effects between group and syllable structure or group and lexical status were found. No significant difference was found on F0 values across time between Tone 1 and Tone 2 syllables in the CAS group. However, interaction effects between group and time points of F0 values on Tone 2 syllables were found. Discussion The results suggest that children with CAS have difficulty with pitch variation, which was revealed on the TST with respect to tone accuracy, consistency, and repetition duration. Moreover, children with CAS have difficulty in varying F0 values to produce high-rising tones and tend to use high-level tones to substitute. Clinically, the TST may be useful to assist in the diagnosis of CAS. Isolated vowel stimuli may be useful to test young children or children with severe impairment. Future investigations and development of a normed tool for children with CAS are suggested.

Joint attention and oromotor abilities in young children with and without autism spectrum disorder.

PURPOSE: This study examined the relationship between joint attention ability and oromotor imitation skill in three groups of young children with and without Autism Spectrum Disorder using both nonverbal oral and verbal motor imitation tasks. Research questions addressed a) differences among joint attention and oromotor imitation abilities; b) the relationship between independently measured joint attention and oromotor imitation, both nonverbal oral and verbal motor; c) the relationships between joint attention and verbal motor imitation during interpersonal interaction; and d) the relationship between the sensory input demands (auditory, visual, and tactile) and oromotor imitation, both nonverbal oral and verbal motor. METHOD: A descriptive, nonexperimental design was used to compare joint attention and oromotor skills of 10 preschool-aged children with ASD, with those of two control groups: 6 typically developing children (TD), and 6 children with suspected Childhood Apraxia of Speech (sCAS) or apraxic-like symptoms. All children had at least a 3.0 mean length utterance. RESULTS: Children with ASD had poorer joint attention skills overall than children with sCAS or typically developing children. Typically developing children demonstrated higher verbal motor imitation skills overall compared to children with sCAS. Correlational analyses revealed that nonverbal oral imitation and verbal motor imitation were positively related to joint attention abilities only in the children with ASD. Strong positive relationships between joint attention in a naturalistic context (e.g., shared story experience) and oromotor imitation skills, both nonverbal oral and verbal motor, were found only for children with ASD. These data suggest there is a strong positive relationship between joint attention skills and the ability to sequence nonverbal oral and verbal motor movements in children with ASD. The combined sensory input approach involving auditory, visual, and tactile modalities contributed to significantly higher nonverbal oral and verbal motor imitation performance for all groups of children. CONCLUSIONS: Verbal children with ASD in this study had difficulties with both the social and cognitive demands of oromotor imitation within a natural environment that demanded cross-modal processing of incoming stimuli within an interpersonal interaction. Further, joint attention and oral praxis may serve as components of an important coupling mechanism in the development of spoken communication and later developing socialcognitive skills.

Motor speech skills in children with Down syndrome: A descriptive study.

PURPOSE: Motor speech characteristics of children with Down syndrome (DS) have historically been viewed as either Childhood Dysarthria (CD) or, more infrequently, as Childhood Apraxia of Speech (CAS). The objective of this study was to investigate motor speech deficits in a systematic manner, considering characteristics from both CAS and CD. METHOD: Motor speech assessments were carried out on seven 3;4-8;11-year old children with DS in comparison with younger, typically-developing children using a Language-Neutral Assessment of Motor Speech for young children (LAMS). Additionally, the motor speech and non-speech oral motor skills of all participants were analysed qualitatively using an investigator checklist of characteristics of CAS, CD and Motor Speech Disorder-Not Otherwise Specified (MSD-NOS). RESULT: Results indicated that the children with DS exhibited symptoms of CAS, CD and MSD-NOS, with variability within the group and overlapping symptoms of the disorder types. This finding is different from previous assumptions that children with DS have either CD or CAS. CONCLUSION: The motor speech disorder accompanying DS is complex. The data provide some preliminary descriptions of motor speech disorders in this population and some tools that clinicians would find useful when assessing motor speech skills of young children with DS.

7q11.23 Duplication syndrome: Physical characteristics and natural history.

In order to describe the physical characteristics, medical complications, and natural history of classic 7q11.23 duplication syndrome [hereafter Dup7 (MIM 609757)], reciprocal duplication of the region deleted in Williams syndrome [hereafter WS (MIM 194050)], we systematically evaluated 53 individuals aged 1.25-21.25 years and 11 affected adult relatives identified in cascade testing. In this series, 27% of probands with Dup7 had an affected parent. Seven of the 26 de novo duplications that were examined for inversions were inverted; in all seven cases one of the parents had the common inversion polymorphism of the WS region. We documented the craniofacial features of Dup7: brachycephaly, broad forehead, straight eyebrows, broad nasal tip, low insertion of the columella, short philtrum, thin upper lip, minor ear anomalies, and facial asymmetry. Approximately 30% of newborns and 50% of older children and adults had macrocephaly. Abnormalities were noted on neurological examination in 88.7% of children, while 81.6% of MRI studies showed structural abnormalities such as decreased cerebral white matter volume, cerebellar vermis hypoplasia, and ventriculomegaly. Signs of cerebellar dysfunction were found in 62.3%, hypotonia in 58.5%, Developmental Coordination Disorder in 74.2%, and Speech Sound Disorder in 82.6%. Behavior problems included anxiety disorders, ADHD, and oppositional disorders. Medical problems included seizures, 19%; growth hormone deficiency, 9.4%; patent ductus arteriosus, 15%; aortic dilation, 46.2%; chronic constipation, 66%; and structural renal anomalies, 18%. We compare these results to the WS phenotype and offer initial recommendations for medical evaluation and surveillance of individuals who have Dup7.

Children with 7q11.23 duplication syndrome: psychological characteristics.

To begin to delineate the psychological characteristics associated with classic 7q11.23 duplication syndrome (duplication of the classic Williams syndrome region; hereafter classic Dup7), we tested 63 children with classic Dup7 aged 4-17 years. Sixteen toddlers aged 18-45 months with classic Dup7 and 12 adults identified by cascade testing also were assessed. For the child group, median General Conceptual Ability (similar to IQ) on the Differential Ability Scales-II was 85.0 (low average), with a range from severe disability to high average ability. Median reading and mathematics achievement standard scores were at the low average to average level, with a range from severe impairment to high average or superior ability. Adaptive behavior was considerably more limited; median Scales of Independent Behavior-Revised Broad Independence standard score was 62.0 (mild impairment), with a range from severe adaptive impairment to average adaptive ability. Anxiety disorders were common, with 50.0% of children diagnosed with Social Phobia, 29.0% with Selective Mutism, 12.9% with Separation Anxiety Disorder, and 53.2% with Specific Phobia. In addition, 35.5% were diagnosed with Attention Deficit/Hyperactivity Disorder and 24.2% with Oppositional Defiant Disorder or Disruptive Behavior Disorder-Not Otherwise Specified. 33.3% of the children screened positive for a possible Autism Spectrum Disorder and 82.3% were diagnosed with Speech Sound Disorder. We compare these findings to previously reported results for children with Williams syndrome and argue that genotype/phenotype studies involving the Williams syndrome region offer important opportunities to understand the contribution of genes in this region to common disorders affecting the general population.

Children with 7q11.23 Duplication Syndrome: Speech, Language, Cognitive, and Behavioral Characteristics and their Implications for Intervention.

7q11.23 duplication syndrome is a recently-documented genetic disorder associated with severe speech delay, language delay, a characteristic facies, hypotonia, developmental delay, and social anxiety. Developmentally appropriate nonverbal pragmatic abilities are demonstrated in socially comfortable situations. Motor speech disorder (Childhood Apraxia of Speech and/or dysarthria), oral apraxia, and/or phonological disorder or symptoms of these disorders are common as are characteristics consistent with expressive language disorder. Intensive speech/language therapy is critical for maximizing long-term outcomes.