Computer-assisted syllable analysis of continuous speech as a measure of child speech disordera).

In this study, a computer-driven, phoneme-agnostic method was explored for assessing speech disorders (SDs) in children, bypassing traditional labor-intensive phonetic transcription. Using the SpeechMark® automatic syllabic cluster (SC) analysis, which detects sequences of acoustic features that characterize well-formed syllables, 1952 American English utterances of 60 preschoolers were analyzed [16 with speech disorder present (SD-P) and 44 with speech disorder not present (SD-NP)] from two dialectal areas. A four-factor regression analysis evaluated the robustness of seven automated measures produced by SpeechMark® and their interactions. SCs significantly predicted SD status (p < 0.001). A secondary analysis using a generalized linear model with a negative binomial distribution evaluated the number of SCs produced by the groups. Results highlighted that children with SD-P produced fewer well-formed clusters [incidence rate ratio (IRR) = 0.8116, p ≤ 0.0137]. The interaction between speech group and age indicated that the effect of age on syllable count was more pronounced in children with SD-P (IRR = 1.0451, p = 0.0251), suggesting that even small changes in age can have a significant effect on SCs. In conclusion, speech status significantly influences the degree to which preschool children produce acoustically well-formed SCs, suggesting the potential for SCs to be speech biomarkers for SD in preschoolers.

A retrospective analysis of factors affecting speech production in school-aged children with cleft palate (+- cleft lip).

OBJECTIVE: The present investigation examined how factors such as cleft type, age of primary palatal surgery, diagnosed syndromes, hearing problems, and malocclusions could predict persistent speech difficulties and the need for speech services in school-aged children with cleft palate. METHODS: Participants included 100 school-aged children with cleft palate. Americleft speech protocol was used to assess the perceptual aspects of speech production. The logistic regression was performed to evaluate the impact of independent variables (IV) on the dependent variables (DV): intelligibility, posterior oral CSCs, audible nasal emission, hypernasality, anterior oral CSCs, and speech therapy required. RESULTS: Sixty-five percent of the children were enrolled in (or had received) speech therapy. The logistic regression model shows a good fit to the data for the need for speech therapy (Hosmer and Lemeshow's χ2(8)=9.647,p=.291). No IVs were found to have a significant impact on the need for speech therapy. A diagnosed syndrome was associated with poorer intelligibility (Pulkstenis-Robinson's χ2(11)=7.120,p=.789). Children with diagnosed syndromes have about six times the odds of a higher hypernasality rating (Odds Ratio = 5.703) than others. The cleft type was significantly associated with audible nasal emission (Fisher'sexactp=.006). At the same time, malocclusion had a significant association with anterior oral CSCs (Fisher'sexactp=.005). CONCLUSIONS: According to the latest data in the Cleft Registry and Audit Network Annual Report for the UK, the majority of children with cleft palate attain typical speech by age five. However, it is crucial to delve into the factors that may influence the continuation of speech disorders beyond this age. This understanding is vital for formulating intervention strategies aimed at mitigating the long-term effects of speech disorders as individuals grow older.

Wireless Mouth Motion Recognition System Based on EEG-EMG Sensors for Severe Speech Impairments.

This study aims to demonstrate the feasibility of using a new wireless electroencephalography (EEG)-electromyography (EMG) wearable approach to generate characteristic EEG-EMG mixed patterns with mouth movements in order to detect distinct movement patterns for severe speech impairments. This paper describes a method for detecting mouth movement based on a new signal processing technology suitable for sensor integration and machine learning applications. This paper examines the relationship between the mouth motion and the brainwave in an effort to develop nonverbal interfacing for people who have lost the ability to communicate, such as people with paralysis. A set of experiments were conducted to assess the efficacy of the proposed method for feature selection. It was determined that the classification of mouth movements was meaningful. EEG-EMG signals were also collected during silent mouthing of phonemes. A few-shot neural network was trained to classify the phonemes from the EEG-EMG signals, yielding classification accuracy of 95%. This technique in data collection and processing bioelectrical signals for phoneme recognition proves a promising avenue for future communication aids.

Comparing classic-onset corticobasal syndrome to speech/language-onset corticobasal syndrome.

INTRODUCTION: Patients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present with speech and/or language (SL) problems and several years later develop CBS (i.e., SL-onset CBS). We aimed to compare clinical, neuroimaging and pathological characteristics of classic-onset CBS with SL-onset CBS. METHODS: We conducted a retrospective cohort study of 62 patients who met criteria for CBS (17 presented with classic-onset CBS and 45 had SL-onset CBS). We compared demographics, clinical characteristics, and grey and white matter volume loss with SPM12 between groups and assessed pathology and corticobasal degeneration (CBD) pathological lesion counts in patients who had died and undergone autopsy. RESULTS: Median age at CBS diagnosis was 66.4 years in classic-onset CBS and 73.6 years in SL-onset CBS. Classic-onset CBS had higher frequencies of dystonia, myoclonus, and alien limb phenomenon, while SL-onset CBS had a higher frequency of vertical supranuclear gaze palsy. Both groups showed smaller frontoparietal volumes than controls, with SL-onset CBS having greater volume loss in the left supplementary motor area than classic-onset CBS. All three classic-onset CBS cases with autopsy (100 %) had CBD pathology while 8/21 of SL-onset CBS cases (38 %) had CBD. Pathological lesion burden (including astrocytic plaques) did not differ between classic-onset and SL-onset CBS. CONCLUSION: Classic-onset and SL-onset CBS appear to be different syndromes, with the former being a more profuse motor syndrome. The more widespread volume loss in SL-onset CBS likely reflects longer disease course.

Clinical and functional characteristics of children and young adults with cerebral palsy and co-occurring attention-deficit/hyperactivity disorder.

BACKGROUND: Emerging research shows that children and young adults (CYAs) with cerebral palsy (CP) are at higher risk for attention-deficit/hyperactivity disorder (ADHD). However, little is known about the clinical and functional characteristics of CYAs with these co-occurring disorders. AIM: To estimate associations between a diagnosis of ADHD among CYAs with CP and clinical and functional characteristics. METHODS: This retrospective, cross-sectional study used data from the electronic health records of CYAs (aged 4-26 years) with CP (n = 1145). We used bivariate and multivariable analyses to estimate associations between an ADHD diagnosis, CP type, Gross Motor Function Classification System (GMFCS) level, speech or language disorder, and intellectual disability. RESULTS: 18.1 % of CYAs with CP had a diagnosis of ADHD. CYAs with spastic-bilateral CP had lower odds of ADHD (adjusted odds ratio [AOR] = 0.58; 95 % confidence interval [CI], 0.35-0.96). Odds of having ADHD were significantly lower for those with GMFCS levels III-V (AOR = 0.10; 95 % CI, 0.06-0.15). CONCLUSIONS: Our study found that a diagnosis of ADHD among CYAs with CP was associated with greater clinical and functional impairments compared to counterparts without ADHD. Findings highlight the need to screen for both conditions because of the high comorbidity rates in this population.

[Universal scoring system for assessing speech function in patients with cleft palate at the stages of surgical treatment]. / Universal'naya ball'naya sistema otsenki rechevoi funktsii u patsientov s rasshchelinoi neba na etapakh khirurgicheskogo lecheniya.

OBJECTIVE: To develop a universal system for assessing the speech function in patients with congenital palatal cleft in the postoperative period. MATERIALS AND METHODS: A universal system for assessing the speech function for patients with a palatal cleft can be applied both after the primary operation of uranoplasty and for patients diagnosed with velopharyngeal insufficiency (VPI). The patient's speech is assessed according to the following criteria: defects in the pronunciation of consonants by place of articulation: labial, labiodental, lingual-dental, lingual-palatal, lingual-alveolar; speech breathing; tongue position; directed air stream; voicing disorders; The patient's is also evaluated for the following findings: hypernasality (reflected speech); hypernasality (spontaneous speech); hyponasality; pharyngeal reflex; audible nasal emission/turbulence; facial grimaces; speech intelligibility. The speech therapy and dental assessments are added to obtain a value characterizing the patient's condition: from 0 to 10 scoring indicates than only speech therapy correction is needed; from 11 to 18 - the decision on the necessity of surgical treatment is made by the surgeon together with the speech therapist, from 18 to 25 - surgical treatment is necessary with subsequent sessions with a speech therapist. RESULTS: With the help of this questionnaire, the operating surgeon can more accurately and objectively assess in dynamics the result of the surgical treatment, regardless of the results of speech therapy treatment in the postoperative period. The creation of this scoring system for speech assessment is aimed at objectivizing the results of uranoplasty and speech-improving operations. It allows the surgeon to compare the effectiveness of different surgical methods. CONCLUSION: The universal scoring system for assessing the state of speech function can be applied in the diagnosis of a patient with a palatal cleft both after the primary operation on the palate and after corrective surgical interventions. It allows monitoring progress and identifying dynamics in surgical and speech therapy treatment.

Longitudinal Speech and Fistula Outcomes Following Primary Cleft Palate Repair at a Single Institution.

INTRODUCTION: Fistula formation and velopharyngeal insufficiency (VPI) are complications of cleft palate repair that often require surgical correction. The goal of the present study was to examine a single institution's experience with cleft palate repair with respect to fistula formation and need for surgery to correct velopharyngeal dysfunction. METHODS: Institutional review board approval was obtained. Patient demographics and operative details over a 10-year period were collected. Primary outcomes measured were development of fistula and need for surgery to correct VPI. Chi-square tests and independent t tests were utilized to determine significance (0.05). RESULTS: Following exclusion of patients without enough information for analysis, 242 patients were included in the study. Fistulas were reported in 21.5% of patients, and surgery to correct velopharyngeal dysfunction was needed in 10.7% of patients. Two-stage palate repair was associated with need for surgery to correct VPI (P = 0.014). Furlow palatoplasty was associated with decreased rate of fistula formation (P = 0.002) and decreased need for surgery to correct VPI (P = 0.014). CONCLUSION: This study reiterates much of the literature regarding differing cleft palate repair techniques. A 2-stage palate repair is often touted as having less growth restriction, but the present study suggests this may yield an increased need for surgery to correct VPI. Prior studies of Furlow palatoplasty have demonstrated an association with higher rates of fistula formation. The present study demonstrated a decreased rate of fistula formation with the Furlow technique, which may be due to the use of the Children's Hospital of Philadelphia modification. This study suggests clinically superior outcomes of the Furlow palatoplasty over other techniques.

Funcionalidade de pessoas hospitalizados em vulnerabilidade comunicativa pela CIF / Functioning of hospitalized people in vulnerable communication by the ICF / Funcionalidad de las personas hospitalizadas con vulnerabilidad comunicativa por el CIF

Introdução: Pacientes hospitalizados, por causas diversas, podem apresentar comprometimentos de fala e linguagem que os coloquem em situação de vulnerabilidade comunicativa, influenciando sua funcionalidade. Adota-se a Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) para análise, sob esta perspectiva. Objetivo: Analisar a linguagem e funcionalidade de pessoas em vulnerabilidade comunicativa, em cuidados intensivo e semi-intensivo no hospital, pela CIF, como base conceitual. Método: Estudodescritivo e transversal, constituído por 18 participantes. Para a coleta de dados realizou-se: (i) levantamento dos prontuários, para caracterização do perfil sociodemográfico e das condições clínicas dos participantes; (ii) aplicação do protocolo ICUCS (Intensive Care Unit Communication Screening Protocol);(iii) introdução da Comunicação Suplementar e/ou Alternativa (CSA) e (iv) diário de campo (registro dos relatos). Os resultados foram analisados pela CIF e realizada análise estatística descritiva. Resultados: A maioria dos participantes estava alerta e compreendia comandos simples, sendo que 39% apresentaram problema grave de expressão de linguagem. Quanto à atividade e participação, 50% apresentaram dificuldade grave no falar, 33%, em iniciar e em manter conversas. Quanto aos fatores ambientais, familiares e profissionais de Saúde foram apontados tanto como facilitadores quanto como barreiras para a comunicação. A CSA foi vista como facilitadora da comunicação. Conclusão: Os participantes apresentaram alteração de expressão da linguagem oral, com compreensão preservada e dificuldades de atividade e participação, com impacto nos fatores ambientais, sendo a CSA uma facilitadora da comunicação. Reafirma-se a aplicabilidade da CIF no contexto hospitalar, para pessoas em vulnerabilidade comunicativa, para cuidado ampliado e humanizado.

Introduction: Hospitalized patients, due to various causes, may present impairment of speech and language which may lead them to a situation of communicative vulnerability, influencing its functioning. The ICF - International Classification of functioning, Disability and Health is adopted to perform this analysis, under this perspective. Purpose: To analyze the language and functioning of people in communicative vulnerability, under intensive or semi-intensive care at the hospital, according to ICF, as a concept basis. Methods: Descriptive and cross-sectional study, composed by 18 participants. Data collected through: (i) hospital chart survey analysis, in order to characterize sociodemographic profile and clinical conditions of the participants; (ii) application of ICUCS - Intensive Care Unit Communication Screening Protocol; (iii) introduction of AAC - Augmentative and Alternative Communication and (iv) field journal (entries of reports). The results were analyzed by ICF and then performed descriptive statistic analyses. Results: Most participants were alert and could comprehend simple commands, from which 39% presented severe problems regarding language expression. Regarding activity and participation, 50% presented severe difficulty of speaking and 33% of starting and keeping conversations. Regarding environmental, family and health professionals factors, they have all been appointed both as facilitators and barriers to communication. AAC was seen as a communication facilitator. Conclusion: Participants presented alteration of oral language expression, preserved comprehension and difficulties in activity and participation with impact in environmental factors, being AAC a communication facilitator. Reassurance of applicability of ICF in hospital context, directed to people in communicative vulnerability, regarding ample and humanized treatment.

Los pacientes hospitalizados, por las causas diversas, pueden presentar deterioro de la funcionalidad del habla y del lenguaje que se sitúa en el discurso comunicativo, lo que influye en su funcionalidad. Se utiliza la Clasificación Internacional del Funcionamiento de la Discapacidad y de la Salud (CIF) para análisis desde esta perspectiva. Objetivo: Analizar el lenguaje y la funcionalidad de personas en vulnerabilidad comunicativa, en cuidados intensivos y semiintensivos hospitalarios, utilizando la CIF, como fundamento conceptual. Método: Estudiodescriptivo y transversal, con 18 participantes. La recogida de datos incluyó: (i) estudios de las historias clínicas, para caracterizar el perfil sociodemográfico y las condiciones clínicas de los participantes; (ii) la aplicación del protocolo ICUCS (Intensive Care Unit Communication Screening Protocol);(iii) la introducción de la Comunicación Aumentativa y Alternativa (CAA) y (iv) un diario de campo (registro de informes). Los resultados se analizaron por la CIF y se realizó un análisis estadístico descriptivo. Resultados: La mayoría de los participantes estaban alerta y entendían órdenes sencillas, el 39% presentaron graves problemas para expresarse en el lenguaje. Em cuanto, a la actividad y la participación, el 50% tenía graves dificultades para hablar, y el 33%, para iniciar y mantener conversaciones. Los factores ambientales, los miembros de la familia y los profesionales sanitarios fueron identificados tanto como facilitadores como obstáculo para la comunicación. Se consideró que el CAA facilitaba la comunicación. Conclusión: Los participantes presentaban alteración en la expresión del lenguaje oral, con entendimiento resguardado y dificultades en la actividad y la participación, con impacto en los factores ambientales, siendo la CAA facilitadora de la comunicación. Se reafirma la aplicabilidad de la CIF en el contexto hospitalario, para personas en vulnerabilidad comunicativa, para la atención ampliada y humanizada.

Velopharyngeal dysfunction and speech-related characteristics in craniofacial microsomia: a retrospective analysis of 223 patients.

This study aimed to document the prevalence, severity, and risk factors of velopharyngeal dysfunction (VPD) in craniofacial microsomia (CFM) and to analyse differences in VPD-related speech characteristics between CFM patients without cleft lip and/or palate (CL/P), CFM patients with CL/P, and CL/P patients without CFM (control). A total of 223 patients with CFM were included, of whom 59 had a CL/P. Thirty-four CFM patients had VPD, including 20 with a CL/P. VPD was significantly more prevalent in CFM with CL/P than in CFM without CL/P (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.9-8.7; P < 0.001). Multivariate logistic regression showed a significant association between CL/P and VPD in CFM patients (OR 7.4, 95% CI 2.1-26.3; P = 0.002). The presence of VPD was not associated with sex, the laterality or severity of CFM. Speech problems related to VPD appeared to be similar among the different groups (CFM without CL/P, CFM with CL/P, CL/P without CFM). As 15.2% of all CFM patients and 8.5% of CFM patients without CL/P had VPD, it is proposed that all patients with CFM, with or without CL/P, should be assessed by a speech and language therapist for the potential risk of VPD.

A case report of a patient with neurodevelopmental disorder with impaired speech and hyperkinetic movements: A biallelic variant in the ZNF142 gene.

Biallelic pathogenic variations in the zinc finger protein 142 (ZNF142) gene are associated with neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM). This disorder is characterized by developmental delay, intellectual disability, speech delay, and movement disorders such as dystonia, tremor, ataxia, and chorea. Here, we report a patient who exhibited common neurological features and rarely reported brain MRI findings. Exome sequencing identified a novel biallelic variant in ZNF142 (c.3528_3529delTG; p.C1176fs*5 (NM_001105537.4)). NEDISHM was first described by Khan et al. (2019) and has been reported in 39 patients to date. Furthermore, upon reviewing our in-house data covering 750 individuals, we identified three different pathogenic ZNF142 variants. It appears that the frequency of ZNF142 alleles is not as low as initially thought, suggesting that this gene should be included in new generation sequencing panels for similar clinical scenarios. Our goal is to compile and expand upon the clinical features observed in NEDISHM, providing novel insights and presenting a new variant to the literature. We also aim to demonstrate that ZNF142 pathogenic variants should be considered in neurodevelopmental diseases.

[Analysis of language and influencing factors of children with speech disorder in Beijing].

Objective: To investigate the features and influencing factors of language in children with various types of speech disorders. Methods: A case-control study was carried out, 262 children with speech disorder had been diagnosed at the language-speech clinic of the Center of Children's Healthcare, Children's Hospital, Capital Institute of Pediatrics from January 2021 to November 2023, the children with speech sound disorder as the speech sound disorder group, the children with developmental stuttering as the stuttering group. There were 100 typically-developed children who underwent physical checkups at the Center of Healthcare during the same period as the healthy group. All children experienced a standardized evaluation of language with diagnostic receptive and expressive assessment of mandarin-comprehensive(DREAM-C) and questionnaire, One-way ANOVA and LSD test were conducted to compare the differences in overall language, receptive language, expressive language, semantics, and syntax scores among 3 groups of children. According to the results of DREAM-C, the children with speech disorder were divided into language normal group and language delay group. Chi-square test and multivariate Logistic regression were implemented to analyze the association between the linguistic development of children with speech disorder and potential influential factors. Results: There were 145 children in the speech sound disorder group, including 110 males and 35 females respectively, with an age of (5.9±1.0) years; 117 children in the stuttering group, including 91 males and 26 females, with an age of (5.8±1.0) years; 100 children in the healthy group, including 75 males and 25 females, with an age of (5.7±1.2) years. The variations in overall language, expressive language, and syntax scores among 3 groups of children were statistically significant (92±18 vs.96±11 vs. 98±11, 81±18 vs. 84±14 vs. 88±13, 87±16 vs. 89±11 vs. 91±10, F=5.46, 4.69, 3.68, all P<0.05). Pairwise comparison revealed that the speech sound disorder group had lower scores in overall language, expressive language, and syntactic compared to the healthy group, and the differences were statistically significant (all P<0.01) and the overall language score was lower than that of children with stuttering (P<0.05). In terms of overall language and expressive language, there was a statistically significant difference in the incidence of language delay among the three groups of children (15.9% (23/145) vs. 20.5% (24/117) vs. 7.0% (7/100), 46.2% (67/145) vs. 39.3% (46/117) vs. 26.0% (26/100); χ2=7.93, 10.28; both P<0.05). In terms of overall language, the stuttering group took up the highest proportion. In terms of expressive language, the speech sound disorder group accounted for the highest amount. The incidence of language delay in children with speech disorder was 44.3% (116/262). Non-parent-child reading, daily screen time ≥1 hour and screen exposure before 1.5 years of age are risk factors for the development of language in children with speech disorder (OR=1.87, 2.18, 2.01; 95%CI 1.07-3.27, 1.23-3.86, 1.17-3.45; all P<0.01). Negative family history are protective factors for the progress of language ability (OR=0.37, 95%CI 0.17-0.81, P<0.05). Conclusions: Children with speech disorder tend to have easy access to language delay, especially in expressive language and syntax. The occurrence of language delay in children with speech disorder is tightly connected with factors such as the family medical history, parent-child reading, screen time, etc. Attention should be paid to the development of language in children who suffer from speech disorder.

Improving Dysarthric Speech Segmentation With Emulated and Synthetic Augmentation.

Acoustic features extracted from speech can help with the diagnosis of neurological diseases and monitoring of symptoms over time. Temporal segmentation of audio signals into individual words is an important pre-processing step needed prior to extracting acoustic features. Machine learning techniques could be used to automate speech segmentation via automatic speech recognition (ASR) and sequence to sequence alignment. While state-of-the-art ASR models achieve good performance on healthy speech, their performance significantly drops when evaluated on dysarthric speech. Fine-tuning ASR models on impaired speech can improve performance in dysarthric individuals, but it requires representative clinical data, which is difficult to collect and may raise privacy concerns. This study explores the feasibility of using two augmentation methods to increase ASR performance on dysarthric speech: 1) healthy individuals varying their speaking rate and loudness (as is often used in assessments of pathological speech); 2) synthetic speech with variations in speaking rate and accent (to ensure more diverse vocal representations and fairness). Experimental evaluations showed that fine-tuning a pre-trained ASR model with data from these two sources outperformed a model fine-tuned only on real clinical data and matched the performance of a model fine-tuned on the combination of real clinical data and synthetic speech. When evaluated on held-out acoustic data from 24 individuals with various neurological diseases, the best performing model achieved an average word error rate of 5.7% and a mean correct count accuracy of 94.4%. In segmenting the data into individual words, a mean intersection-over-union of 89.2% was obtained against manual parsing (ground truth). It can be concluded that emulated and synthetic augmentations can significantly reduce the need for real clinical data of dysarthric speech when fine-tuning ASR models and, in turn, for speech segmentation.

Speech Outcomes of Frenectomy for Tongue-Tie Release: A Systematic Review and Meta-Analysis.

OBJECTIVE: Tongue-tie, which is also known as ankyloglossia, is a common condition where the lingual frenulum is unusually tight or short. While most literature investigates the impact of tongue-tie on breastfeeding, recent articles have examined its role in speech production in children. However, these have not previously been reviewed systematically. This study aims to determine the impact of tongue-tie on speech outcomes and assess whether frenectomy can improve speech function. METHODS: In this systematic review, we conducted a comprehensive search of PubMed/MEDLINE, Cochrane Library, Embase, and speechBITE to analyze primary studies investigating the impact of frenectomy for tongue-tie on speech outcomes. We extracted data regarding patient age, male to female ratio, procedure type, follow-up time, and speech outcomes and ran statistical analyses to determine if frenectomy for tongue-tie leads to improvement in speech issues in pediatric patients. Speech outcomes extracted were subjectively measured based on the interpretation of a speech and language pathologist or parent. RESULTS: Our analysis included 10 studies with an average patient age of 4.10 years, and average cohort size of 22.17 patients. Overall, frenectomy for tongue-tie was associated with an improvement in speech articulation (0.78; 95% CI: 0.64-0.87; P < .01). Increasing patient age was found to be negatively correlated with post-frenectomy speech outcomes (P = .01). However, this relationship disappeared in the adjusted model. CONCLUSION: Overall, we conclude that frenectomy is a suitable treatment to correct speech issues in select patients with tongue-tie if caught early in childhood. Despite the limited investigations around speech outcomes post-frenectomy, these results are informative to providers treating tongue-tie.

ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes.

Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGAT), encoded by GATM, which are involved in the synthesis of creatine. After synthesis, creatine is taken up by a sodium-dependent membrane bound creatine transporter (CRTR), encoded by SLC6A8, into all organs. Creatine uptake is very important especially in high energy demanding organs such as the brain, and muscle. To classify the pathogenicity of variants in GAMT, GATM, and SLC6A8, we developed the CCDS Variant Curation Expert Panel (VCEP) in 2018, supported by The Clinical Genome Resource (ClinGen), a National Institutes of Health (NIH)-funded resource. We developed disease-specific variant classification guidelines for GAMT-, GATM-, and SLC6A8-related CCDS, adapted from the American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant interpretation guidelines. We applied specific variant classification guidelines to 30 pilot variants in each of the three genes that have variants associated with CCDS. Our CCDS VCEP was approved by the ClinGen Sequence Variant Interpretation Working Group (SVI WG) and Clinical Domain Oversight Committee in July 2022. We curated 181 variants including 72 variants in GAMT, 45 variants in GATM, and 64 variants in SLC6A8 and submitted these classifications to ClinVar, a public variant database supported by the National Center for Biotechnology Information. Missense variants were the most common variant type in all three genes. We submitted 32 new variants and reclassified 34 variants with conflicting interpretations. We report specific phenotype (PP4) using a points system based on the urine and plasma guanidinoacetate and creatine levels, brain magnetic resonance spectroscopy (MRS) creatine level, and enzyme activity or creatine uptake in fibroblasts ranging from PP4, PP4_Moderate and PP4_Strong. Our CCDS VCEP is one of the first panels applying disease specific variant classification algorithms for an X-linked disease. The availability of these guidelines and classifications can guide molecular genetics and genomic laboratories and health care providers to assess the molecular diagnosis of individuals with a CCDS phenotype.

Exploring Motor Speech Disorders in Low and Minimally Verbal Autistic Individuals: An Auditory-Perceptual Analysis.

PURPOSE: Motor deficits are widely documented among autistic individuals, and speech characteristics consistent with a motor speech disorder have been reported in prior literature. We conducted an auditory-perceptual analysis of speech production skills in low and minimally verbal autistic individuals as a step toward clarifying the nature of speech production impairments in this population and the potential link between oromotor functioning and language development. METHOD: Fifty-four low or minimally verbal autistic individuals aged 4-18 years were video-recorded performing nonspeech oromotor tasks and producing phonemes, syllables, and words in imitation. Three trained speech-language pathologists provided auditory perceptual ratings of 11 speech features reflecting speech subsystem performance and overall speech production ability. The presence, attributes, and severity of signs of oromotor dysfunction were analyzed, as were relative performance on nonspeech and speech tasks and correlations between perceptual speech features and language skills. RESULTS AND CONCLUSIONS: Our findings provide evidence of a motor speech disorder in this population, characterized by perceptual speech features including reduced intelligibility, decreased consonant and vowel precision, and impairments of speech coordination and consistency. Speech deficits were more associated with articulation than with other speech subsystems. Speech production was more impaired than nonspeech oromotor abilities in a subgroup of the sample. Oromotor deficits were significantly associated with expressive and receptive language skills. Findings are interpreted in the context of known characteristics of the pediatric motor speech disorders childhood apraxia of speech and childhood dysarthria. These results, if replicated in future studies, have significant potential to improve the early detection of language impairments, inform the development of speech and language interventions, and aid in the identification of neurobiological mechanisms influencing communication development.

Language-Independent Acoustic Biomarkers for Quantifying Speech Impairment in Huntington's Disease.

PURPOSE: Changes in voice and speech are characteristic symptoms of Huntington's disease (HD). Objective methods for quantifying speech impairment that can be used across languages could facilitate assessment of disease progression and intervention strategies. The aim of this study was to analyze acoustic features to identify language-independent features that could be used to quantify speech dysfunction in English-, Spanish-, and Polish-speaking participants with HD. METHOD: Ninety participants with HD and 83 control participants performed sustained vowel, syllable repetition, and reading passage tasks recorded with previously validated methods using mobile devices. Language-independent features that differed between HD and controls were identified. Principal component analysis (PCA) and unsupervised clustering were applied to the language-independent features of the HD data set to identify subgroups within the HD data. RESULTS: Forty-six language-independent acoustic features that were significantly different between control participants and participants with HD were identified. Following dimensionality reduction using PCA, four speech clusters were identified in the HD data set. Unified Huntington's Disease Rating Scale (UHDRS) total motor score, total functional capacity, and composite UHDRS were significantly different for pairwise comparisons of subgroups. The percentage of HD participants with higher dysarthria score and disease stage also increased across clusters. CONCLUSION: The results support the application of acoustic features to objectively quantify speech impairment and disease severity in HD in multilanguage studies. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25447171.

Functional and structural abnormalities of the speech disorders: a multimodal activation likelihood estimation meta-analysis.

Speech disorders are associated with different degrees of functional and structural abnormalities. However, the abnormalities associated with specific disorders, and the common abnormalities shown by all disorders, remain unclear. Herein, a meta-analysis was conducted to integrate the results of 70 studies that compared 1843 speech disorder patients (dysarthria, dysphonia, stuttering, and aphasia) to 1950 healthy controls in terms of brain activity, functional connectivity, gray matter, and white matter fractional anisotropy. The analysis revealed that compared to controls, the dysarthria group showed higher activity in the left superior temporal gyrus and lower activity in the left postcentral gyrus. The dysphonia group had higher activity in the right precentral and postcentral gyrus. The stuttering group had higher activity in the right inferior frontal gyrus and lower activity in the left inferior frontal gyrus. The aphasia group showed lower activity in the bilateral anterior cingulate gyrus and left superior frontal gyrus. Across the four disorders, there were concurrent lower activity, gray matter, and fractional anisotropy in motor and auditory cortices, and stronger connectivity between the default mode network and frontoparietal network. These findings enhance our understanding of the neural basis of speech disorders, potentially aiding clinical diagnosis and intervention.