Genetic bases of stuttering: the state of the art, 2011.

OBJECTIVE: The literature on the genetics of stuttering is reviewed with special reference to the historical development from psychosocial explanations leading up to current biological research of gene identification. SUMMARY: A gradual progression has been made from the early crude methods of counting percentages of stuttering probands who have relatives who stutter to recent studies using entire genomes of DNA collected from each participant. Despite the shortcomings of some early studies, investigators have accumulated a substantial body of data showing a large presence of familial stuttering. This encouraged more refined research in the form of twin studies. Concordance rates among twins were sufficiently high to lend additional support to the genetic perspective of stuttering. More sophisticated aggregation studies and segregation analyses followed, producing data that matched recognized genetic models, providing the final 'go ahead' to proceed from the behavior/statistical genetics into the sphere of biological genetics. Recent linkage and association studies have begun to reveal contributing genes to the disorder. CONCLUSION: No definitive findings have been made regarding which transmission model, chromosomes, genes, or sex factors are involved in the expression of stuttering in the population at large. Future research and clinical implications are discussed.

Prevalence of stuttering in African American preschoolers.

PURPOSE: In this study, the authors sought to determine the prevalence of stuttering in African American (AA) 2- to 5-year-olds as compared with same-age European Americans (EAs). METHOD: A total of 3,164 children participated: 2,223 AAs and 941 EAs. Data were collected using a 3-pronged approach that included investigators' individual interactions with each child, teacher identification, and parent identification of stuttering. RESULTS: No statistically significant difference for stuttering was found between AA and EA children. Using the investigator and teacher method of identification, the prevalence of stuttering was 2.52% for the entire sample. For both racial groups, boys exhibited a higher prevalence of stuttering than girls. Of the 3 predictors (age, race, sex) of stuttering, only sex was a significant predictor. CONCLUSIONS: AA 2- to 5-year-olds are not overrepresented in the stuttering population for this age group. When data are combined for both racial groups, the prevalence of stuttering is 2.52%. More boys than girls stuttered in this sample of preschoolers.

Phonological skills and disfluency levels in preschool children who stutter.

UNLABELLED: The relation between stuttering and aspects of language, including phonology, has been investigated for many years. Whereas past literature reported that the incidence of phonological difficulties is higher for children who stutter when compared to normally fluent children, the suggestion of association between the two disorders also drew several critical evaluations. Nevertheless, only a limited amount of information exists concerning the manner and extent to which the speech sound errors exhibited by young children who stutter, close to stuttering onset, is related to the characteristics of their stuttering, such as its severity. Conversely, information is limited regarding the effects a child's phonological skills may have on his/her stuttering severity. The current study investigated the mutual relations between these two factors in 28 carefully selected preschool children near the onset of their stuttering. The children, 20 boys and 8 girls, ranged in age from 25 to 38 months, with a mean of 32.2 months. The phonological skills of two groups with different ratings of stuttering were compared. Similarly, the stuttering severities of two groups with different levels of phonological skills (minimal deviations-moderate deviations) were compared. No statistically significant differences were found for either of the two factors. Inspection of the data revealed interesting individual differences. LEARNING OUTCOMES: The reader will be able to list: (1) differences in the phonological skills of preschool children whose stuttering is severe as compared to children whose stuttering is mild and (2) differences in stuttering severity in preschool children with minimal phonological deviations as compared to children with moderate phonological deviations.

Subtyping stuttering I: a review.

UNLABELLED: A reliable and practical subtype system of stuttering should enhance all related scientific work concerned with this disorder. Although a fair number of classification systems have been offered, to date, none has received wide recognition or has been routinely applied in research or clinical spheres. Whereas progress has been made in understanding and treating the disorder, for the most part stuttering continues to be viewed and addressed as a unitary problem. The objectives of the current article are to (a) highlight the motivation for identifying sub-types of stuttering, (b) outline the issues involved in researching subtypes, and (c) address the question of whether or not subtyping is plausible for this disorder. Toward these ends, a broad-based review of past concepts regarding subtypes of stuttering and stutterers is presented according to seven categories that reflect the various authors' conceptual or experimental approaches. Selected studies for each category are also presented to illustrate the research problems and challenges. It is concluded that islands of progress can be identified in subtype research, particularly in studies of children. It is recommended that future studies include multiple factors or domains in the data collection process, especially with young children during the formative years of the disorder, when substantial overlap in the development of several speech/language domains occurs. EDUCATIONAL OBJECTIVES: (a) Readers will be able to describe the theory and research concerning the numerous attempts to subtype stuttering, particularly during the past 50 years; (b) Readers will be able to explain the general issues that need to be resolved in order to identify subtypes as well as current and future research strategies aimed at achieving these goals.

Genetic studies of stuttering in a founder population.

UNLABELLED: Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180-195 cM) and 5 (P=0.0051, 105-120 cM; P=0.015, 120-135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta-analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. EDUCATIONAL OBJECTIVES: After reading this article, the reader will be able to: (1) summarize information about the background of common disorders and methodology of genetic studies; (2) evaluate the role of genetics in stuttering; (3) discuss the value of using founder populations in genetic studies; (4) articulate the importance of combining several studies in a meta-analysis; (5) discuss the overlap of genetic signals identified in stuttering with other speech and language disorders.

Identification of traits associated with stuttering.

UNLABELLED: Stuttering has been considered a heritable disorder since the 1930s. There have been different models of transmission that have been proposed most involving a polygenic component with or without a major locus. In spite of these models, the characteristics being transmitted are not known. This study used two different tasks-a tapping task that is thought to probe hemispheric differences and a Stroop task, which appears to create interferences in speech motor programming and/or execution. The 48 participants in this study included individuals who stutter, high risk family members and controls for each group. Results indicated that for tapping at a comfortable rate, the experimental groups were significantly different from their control groups and for tapping at a fast rate, the stuttering and high risk groups were different from each other. The results of the Stroop test were not statistically significant. LEARNING OUTCOMES: Readers will learn about: (1) genetic aspects of stuttering; (2) hemispheric dominance in stuttering and high risk subjects; (3) understanding traits that may be associated with stuttering.

The effect of sample size on the assessment of stuttering severity.

The relationships between the length of the speech sample and the resulting disfluency data in 20 stuttering children who exhibited a wide range of disfluency levels were investigated. Specifically, the study examined whether the relative number of stuttering-like disfluencies (SLD) per 100 syllables, as well as the length of disfluencies (number of iterations per disfluent event), varied systematically across 4 consecutive, 300-syllable sections in the same speech sample. The difference in the number of SLD per 100 syllables between the early and later sections of the speech sample was statistically significant. In addition, the length of the speech sample had a critical influence on the identification of stuttering in children exhibiting relatively low levels of disfluency. Also, when a 20% difference in the number of SLD per 100 syllables was taken as a criterion, 50% of the children exhibited upward shifts in continuous speech samples that were longer than 300 syllables (i.e., 600, 900, and 1,200 syllables). Results indicated that, in general, group means for SLD grew larger as the sample size increased. The length of disfluent events did not significantly differ as the sample size increased; however, there were large differences for some children. Implications for clinicians and investigators are discussed.

Relation of motor, linguistic and temperament factors in epidemiologic subtypes of persistent and recovered stuttering: Initial findings.

PURPOSE: The purpose of this study was to determine the presence of any patterns reflecting underlying subtypes of persistence and recovery across epidemiologic, motor, language, and temperament domains in the same group of children beginning to stutter and followed for several years. METHODS: Participants were 58 2-4-year-old CWS and 40 age and gender matched NFC from four different sites in the Midwest. At the end of the multi-year study, stuttering children were classified as Persistent or Recovered. The same protocol obtaining data to measure stuttering, motor, language and temperament characteristics was used at each site. They have not been included in previous reports. RESULTS: The Persistent group performed consistently differently from the Recovered and Control groups. They performed lower on standardized language tests and in phonological accuracy, had greater kinematic variability, and were judged by their parents to be more negative in temperament. CONCLUSIONS: The present study provides data supporting the hypothesis that subtypes of stuttering can be identified along persistency/recovery lines, but results were not definitive. EDUCATIONAL OBJECTIVES: Readers will be able to (a) describe the current state of subtypes of stuttering research; (b) summarize possible contributions of epidemiologic, motoric, linguistic and temperament to such subtyping with regard to persistency and recovery.

Phonological progress during the first 2 years of stuttering.

This report is the third in a series on phonological impairment in children who stutter, comparing its extent in those whose stuttering will be persistent with those in whom that disorder will disappear spontaneously. The first (E. P. Paden & E. Yairi, 1996) compared small groups of these children with normally fluent children of the same ages and sex. The second (E. P. Paden, E. Yairi, & N. G. Ambrose, 1999) compared the phonological abilities evidenced soon after onset of stuttering for 84 young children. In that study, the mean level of phonological skills of the 22 participants whose stuttering eventually persisted for at least 4 years was found to be significantly poorer than that of 62 others whose stuttering would disappear without fluency intervention before that time. In the present study, recorded performances of the same 84 children, made 1 and 2 years later, were similarly evaluated to determine how their phonological development progressed after the initial visit. Results of assessment at the 1-year visit showed that the mean difference between the two groups of children was no longer significant. The children whose stuttering would persist had improved more phonologically than had those who would recover from stuttering. At the 2-year visit, the mean percentage of phonological error for the two groups was identical. Furthermore, at this assessment, only 3 of the children in the Persistent group and 11 of those in the Recovered group had not essentially mastered all of the 10 basic patterns of phonology that were the focus of our evaluation. The findings concerning the longitudinal covariance of stuttering and phonological skills provide information that should be considered in any attempt to explain the relation between the two.

Prevalence of voice disorders in African American and European American preschoolers.

Several studies have reported prevalence rates for voice disorders in school-aged children. Less is known, however, about such prevalence in preschoolers, and whether racial, ethnic, or cultural diversity may influence it. The presence of voice disorders in a total of 2445 African-American and European-American preschool children, 1246 males and 1199 females, from 2 to 6 years of age is reported here. Presence of a voice disorder characterized by hoarseness was identified by a three-prong approach including teacher identification, investigator screening, and parent identification. Speech-language pathologists listened individually to each child's speech as they engaged each child in play-conversation activities. A voice disorder was identified on the basis of the judgment of two speech-language pathologists. Voice disorders characterized by hoarseness were identified in 95 children or 3.9% of the total sample by the investigators. Statistical analysis revealed no significant differences for age, gender, or race.

The effect of temporal manipulation on the perception of disfluencies as normal or stuttering.

UNLABELLED: The purpose of this investigation was to study the effect of temporal features within repetition of speech segments on the perception of stuttering. Past research has provided evidence that certain temporal aspects of repetitions produced by people who stutter tend to be shorter than those produced by normally fluent speakers. The effect of these temporal factors on the perception of the disfluency as "stuttering" or "normal" has not yet been studied. Conversational speech of five children who stutter was recorded. Two short utterances. one containing part-word repetition (PWR) and one containing whole-word repetition (WWR), were identified in the speech of each child and then manipulated by the CSL and CSpeech computer softwares. Two selected elements within repetitions, namely the vowel of the repeated unit and the interval between the repeated units (e.g., but-but), were lengthened to simulate normal disfluency. Results indicated that both factors (interval duration and vowel duration) moderately affected listeners' perception. In general, repetitions with short vowel and interval durations were judged as more representative of stuttering, whereas repetitions with longer vowel and interval duration were judged as more representative of normal speech. LEARNING OUTCOMES: As a result of this activity, the reader will learn about (1) various factors that influence the perception of disfluent segments as stuttering, (2) the special effect of duration of specific elements within repetitions on the perception of disfluency as stuttering, and (3) the possible implications of the new information for therapeutic considerations.

Second formant transitions in fluent speech of persistent and recovered preschool children who stutter.

UNLABELLED: This study investigated frequency change and duration of the second formant (F2) transitions in perceptually fluent speech samples recorded close to stuttering onset in preschool age children. Comparisons were made among 10 children known to eventually persist in stuttering, 10 who eventually recovered from stuttering, and 10 normally fluent controls. All were enrolled in the longitudinal Stuttering Research Project at the University of Illinois. Subjects fluently repeated standard experimental sentences. The same 36 perceptually fluent target segments (syllables embedded in words) from each subject's repeated sentences were analyzed. The syllables were divided into three phonetic categories based on their initial consonant: bilabial, alveolar, and velar placement. The frequency change and duration of F2 transitions were analyzed for each of the target CV segments. F2 transition onset and offset frequencies and their interval (duration) were measured for each utterance. Data indicate that near stuttering onset, children whose stuttering eventually persisted demonstrated significantly smaller frequency change than that of the recovered group. It is suggested that the F2 transitions should continue to be investigated as a possible predictor of stuttering pathways. LEARNING OUTCOMES: (1) Readers will learn about studies regarding second formant transition related to stuttering. (2) Readers will learn about differences between children who persist in stuttering and those who recover from stuttering. (3) Readers will learn about research concerned with early identification of risk criteria in persistent stuttering.

Defining stuttering for research purposes.

This is a response to a Letter to the Editor entitled "Stuttering prevalence, incidence and recovery rates depend on how we define it: Comment on Yairi & Ambrose' article Epidemiology of Stuttering: 21st Century advances" by Paul Brocklehurst (2013). The criticism was directed specifically toward Yairi and Ambrose' conclusions, based on review of recent studies, regarding the incidence and prevalence of stuttering. In this response, Brocklehurst's arguments and suggestions of criteria for incidence research are discussed and negated.

Epidemiology of stuttering: 21st century advances.

UNLABELLED: Epidemiological advances in stuttering during the current century are reviewed within the perspectives of past knowledge. The review is organized in six sections: (a) onset, (b) incidence, (c) prevalence, (d) developmental paths, (e) genetics and (f) subtypes. It is concluded that: (1) most of the risk for stuttering onset is over by age 5, earlier than has been previously thought, with a male-to-female ratio near onset smaller than what has been thought, (2) there are indications that the lifespan incidence in the general population may be higher than the 5% commonly cited in past work, (3) the average prevalence over the lifespan may be lower than the commonly held 1%, (4) the effects of race, ethnicity, culture, bilingualism, and socioeconomic status on the incidence/prevalence of stuttering remain uncertain, (5) longitudinal, as well as incidence and prevalence studies support high levels of natural recovery from stuttering, (6) advances in biological genetic research have brought within reach the identification of candidate genes that contribute to stuttering in the population at large, (7) subtype-differentiation has attracted growing interest, with most of the accumulated evidence supporting a distinction between persistent and recovered subtypes. EDUCATIONAL OBJECTIVES: Readers will be exposed to a summary presentation of the most recent data concerning basic epidemiological factors in stuttering. Most of these factors also pertain to children's risks for experiencing stuttering onset, as well as risks for persistency. The article also aims to increase awareness of the implications of the information to research, and professional preparation that meets the epidemiology of the disorder.

Disfluency patterns and phonological skills near stuttering onset.

There is a substantial amount of literature reporting the incidence of phonological difficulties to be higher for children who stutter when compared to normally fluent children, suggesting a link between stuttering and phonology. In view of this, the purpose of the investigation was to determine whether, among children who stutter, there are relationships between phonological skills and the initial characteristics of stuttering. That is, close to the onset of stuttering, there are differences in specific stuttering patterns between children who exhibit minimal and moderate phonological deviations in terms of frequency of stuttering and length of stuttering events? Twenty-nine preschool children near the onset of stuttering, ranging in age from 29 to 49 months, with a mean of 39.17 months, were divided into two groups based on the level of phonological ability: minimal phonological deviations and moderate phonological deviations. The children's level of stuttering-like disfluencies was examined. Results revealed no statistically significant differences in the stuttering characteristics of the two groups near onset, calling into the question the nature of the stuttering-phonology link.

Characteristics of disfluency clusters over time in preschool children who stutter.

PURPOSE: Disfluency clusters in preschool children were analyzed to determine whether they occurred at rates above chance, whether they changed over time, and whether they could differentiate children who would later persist in, or recover from, stuttering. METHOD: Thirty-two children recruited near stuttering onset were grouped on the basis of their eventual course of stuttering and matched to 16 normally fluent children. Clusters were classified as stuttering-like disfluencies (SLD), other disfluencies (OD), or mixed (SLD and OD combined). Cluster frequency and length were calculated for all children and again after 6 months for those who stuttered. RESULTS: Clusters occurred at rates greater than chance for both stuttering and normally fluent children. Children who stuttered had significantly more and longer clusters than did normally fluent children. Close to stuttering onset, clusters did not differentiate the course of stuttering. Cluster frequency and length decreased over time for children in the persistent and recovered groups. The proportion of disfluencies in clusters was significantly lower in the recovered group than it was in the persistent group after 6 months. CONCLUSIONS: Clusters are an integral part of disfluent speech in preschool children in general. Although they do not serve as indicators of recovery or persistency at the onset of stuttering, they may have some prognostic value several months later.

New complexities in the genetics of stuttering: significant sex-specific linkage signals.

Stuttering is a speech disorder long recognized to have a genetic component. Recent linkage studies mapped a susceptibility locus for stuttering to chromosome 12 in 46 highly inbred families ascertained in Pakistan. We report here on linkage studies in 100 families of European descent ascertained in the United States, Sweden, and Israel. These families included 252 individuals exhibiting persistent stuttering, 45 individuals classified as recovered from stuttering, and 19 individuals too young to classify. Primary analyses identified moderate evidence for linkage of the broader diagnosis of "ever stuttered" (including both persistent and recovered stuttering) on chromosome 9 (LOD = 2.3 at 60 cM) and of the narrower diagnosis of persistent stuttering on chromosome 15 (LOD = 1.95 at 23 cM). In contrast, sex-specific evidence for linkage on chromosome 7 at 153 cM in the male-only data subset (LOD = 2.99) and on chromosome 21 at 34 cM in the female-only data subset (LOD = 4.5) met genomewide criteria for significance. Secondary analyses revealed a significant increase in the evidence for linkage on chromosome 12, conditional on the evidence for linkage at chromosome 7, with the location of the increased signal congruent with the previously reported signal in families ascertained in Pakistan. In addition, a region on chromosome 2 (193 cM) showed a significant increase in the evidence for linkage conditional on either chromosome 9 (positive) or chromosome 7 (negative); this chromosome 2 region has been implicated elsewhere in studies on autism, with increased evidence for linkage observed when the sample is restricted to those with delayed onset of phrase speech. Our results support the hypothesis that the genetic component to stuttering has significant sex effects.