Wendy Cohen

Highly significant linkage to the SLI1 locus in an expanded sample of individuals affected by specific language impairment

Specific language impairment (SLI) is defined as an unexplained failure to acquire normal language skills despite adequate intelligence and opportunity. We have reported elsewhere a full-genome scan in 98 nuclear families affected by this disorder, with the use of three quantitative traits of language ability (the expressive and receptive tests of the Clinical Evaluation of Language Fundamentals and a test of nonsense word repetition). This screen implicated two quantitative trait loci, one on chromosome 16q (SLI1) and a second on chromosome 19q (SLI2). However, a second independent genome screen performed by another group, with the use of parametric linkage analyses in extended pedigrees, found little evidence for the involvement of either of these regions in SLI. To investigate these loci further, we have collected a second sample, consisting of 86 families (367 individuals, 174 independent sib pairs), all with probands whose language skills are >/=1.5 SD below the mean for their age. Haseman-Elston linkage analysis resulted in a maximum LOD score (MLS) of 2.84 on chromosome 16 and an MLS of 2.31 on chromosome 19, both of which represent significant linkage at the 2% level. Amalgamation of the wave 2 sample with the cohort used for the genome screen generated a total of 184 families (840 individuals, 393 independent sib pairs). Analysis of linkage within this pooled group strengthened the evidence for linkage at SLI1 and yielded a highly significant LOD score (MLS = 7.46, interval empirical P<.0004). Furthermore, linkage at the same locus was also demonstrated to three reading-related measures (basic reading [MLS = 1.49], spelling [MLS = 2.67], and reading comprehension [MLS = 1.99] subtests of the Wechsler Objectives Reading Dimensions).

CMIP and ATP2C2 modulate phonological short-term memory in language impairment

Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.

Severe receptive language disorder in childhood-familial aspects and long-term outcomes : results from a Scottish study

Background and aims: Little is known about the familial characteristics of children with severe receptive specific language impairment (SLI). Affected children are more likely to have long-term problems than those with expressive SLI but to date they have only been described as small cohorts within SLI populations. We therefore aimed to describe the clinical and familial characteristics of severe receptive SLI as defined by a rigorous phenotype and to establish whether non-word repetition showed a relationship with language impairment in these families. Methods: Cross-sectional study of children who met ICD-10 (F80.2) criteria for receptive SLI at school entry, their siblings and genetic parents with standardised measures of language and non-verbal IQ, phonological auditory memory and speech sound inventory. Results: At a mean of 6 years after school entry with a severe receptive SLI, the 58 participants had a normal mean and standard deviation non-verbal IQ, but only 3% (two) had attained language measures in the normal range. One third still had severe receptive language impairment. One third of siblings not known to be affected had language levels outside the normal range. Phonological auditory memory was impaired in most family members. Conclusion: Severe receptive SLI is nearly always associated with an equally severe reduction in expressive language skills. Language impairment in siblings may go undetected and yet they are at high risk. Family members had weak phonological auditory memory skills, suggesting that this could be a marker for language acquisition difficulties. Receptive SLI rarely resolves and trials of therapy are urgently needed.

Development of a minimum protocol for assessment in the paediatric voice clinic. Part 2: Subjective measurement of symptoms of voice disorder

The European Laryngological Society (ELS) recommend that functional assessment of voice disorder in adults requires evaluation of a number of different parameters. These include perceptual evaluation of voice, videostroboscopic imaging of vocal fold movement, acoustic analysis of specific voicing aspects, aerodynamic support for voicing, and a subjective rating of voice impact. No specific guidelines are available for children, but a similar range of parameters is needed to guide intervention and measure outcomes. The development of subjective voice measures for adults and their adaptations for the paediatric population are reviewed and compared to the research comparing these to evaluation of vocal function. The need for further refinement of child assessment measures, and a proposal of how these might be developed, is discussed.

Development of a minimum protocol for assessment in the paediatric voice clinic. Part 1: Evaluating vocal function

The European Laryngological Society (ELS) recommend that functional assessment of voice disorder in adults requires evaluation of a number of different parameters. The current paper presents a discussion of four of the five parameters highlighted in the ELS protocol: perceptual evaluation of voice, videostroboscopic examination, evaluation of aerodynamic performance in voice, and acoustic analysis. Subjective rating of voice in children is explored in a companion paper. These parameters have been extensively evaluated in adults, and a review of the literature pertaining to the paediatric population is presented.

Parent and Child Responses to the Pediatric Voice-Related Quality-of-Life Questionnaire

OBJECTIVES When assessing pediatric dysphonia, there are different approaches that can be taken in gathering a subjective view of the impact voice difficulties have on a child. Most valid questionnaires require parent-proxy reporting, although it has become increasingly important to gather the views of children themselves. This study reports a pilot study of an adaptation to the Pediatric Voice-Related Quality-of-Life Questionnaire (PVRQoL). METHODS A total of 24 parent and child dyads were recruited from a tertiary pediatric voice clinic. Children were aged between 3 years and 8 months and 15 years and 3 months. Parents completed the existing PVRQoL questionnaire, whereas their children were given a child-adapted version. Follow-up completion of the child questionnaire was conducted after a 2-week period. RESULTS There was a good correlation between the two time periods when children completed the adapted PVRQoL and also between parent and child responses. Of particular interest, however, was the different ratings on individual items by parents and their children with parents tending to overestimate the extent to which their children may be emotionally affected by their voice disorder. CONCLUSIONS This study shows that children have much to tell about their own voice-related quality of life, so our conclusion is that they should also be self-assessed. The PVRQoL when adapted for use with children offers an additional insight that can be gathered in a relatively short timeframe and be considered with other assessments of vocal function.

The paediatric voice clinic

Background Prevalence of paediatric voice disorders has been reported as 6–9% in children of school age. The appropriate diagnosis and management of paediatric voice disorders is essential for progress in education and psychosocial development. This paper presents a review of a UK tertiary paediatric voice clinic experience of referral patterns, diagnosis, management and socioeconomic variations. Methods An audit of 195 consecutive appointments (154 were new patients) between October 2009 and September 2013 at a monthly paediatric voice clinic based at the Royal Hospital for Sick Children in Glasgow. Results Of the 154 new patients, 86 were male and 68 were female. The age at first clinic appointment shows a trimodal peak at ages 5, 8 and 11 years. General practitioners were the main referral source (46%). Vocal cord nodules accounted for 52% of diagnoses with a male predominance. Clinic attendance was most common from Scottish Index of Multiple Deprivation groups 1 (most deprived) and 5 (least deprived). Analysis of the muscle tension dysphonia group indicates that they are more likely to come from social groups 4 or 5 (69%) and an older age group (mean age 10.4 years). Discussion A dedicated paediatric voice clinic is the optimal method for assessment, diagnosis and management of these patients. Diagnosis is possible on the majority of the patients in clinic, with the predominant pathology being vocal cord nodules that receive speech and language therapy. Socioeconomic group appears to have an influence on paediatric voice particularly vocal cord nodules and muscle tension dysphonia.

Measuring Word Complexity in Speech Screening: Single-Word Sampling to Identify Phonological Delay/Disorder in Preschool Children.

BACKGROUND Childrens speech sound development is assessed by comparing speech production with the typical development of speech sounds based on a childs age and developmental profile. One widely used method of sampling is to elicit a single-word sample along with connected speech. Words produced spontaneously rather than imitated may give a more accurate indication of a childs speech development. A published word complexity measure can be used to score later-developing speech sounds and more complex word patterns. There is a need for a screening word list that is quick to administer and reliably differentiates children with typically developing speech from children with patterns of delayed/disordered speech. AIMS To identify a short word list based on word complexity that could be spontaneously named by most typically developing children aged 3;00-5;05 years. METHODS & PROCEDURES One hundred and five children aged between 3;00 and 5;05 years from three local authority nursery schools took part in the study. Items from a published speech assessment were modified and extended to include a range of phonemic targets in different word positions in 78 monosyllabic and polysyllabic words. The 78 words were ranked both by phonemic/phonetic complexity as measured by word complexity and by ease of spontaneous production. OUTCOME & RESULTS The ten most complex words (hereafter Triage 10) were named spontaneously by more than 90% of the children. There was no significant difference between the complexity measures for five identified age groups when the data were examined in 6-month groups. A qualitative analysis revealed eight children with profiles of phonological delay or disorder. When these children were considered separately, there was a statistically significant difference (p < 0.005) between the mean word complexity measure of the group compared with the mean for the remaining children in all other age groups. The Triage 10 words reliably differentiated children with typically developing speech from those with delayed or disordered speech patterns. CONCLUSIONS & IMPLICATIONS The Triage 10 words can be used as a screening tool for triage and general assessment and have the potential to monitor progress during intervention. Further testing is being undertaken to establish reliability with children referred to speech and language therapy services.

Cross-sectional follow-up of voice outcomes in children who have a history of airway reconstruction surgery

This study reports vocal function in a cross‐section of children with subglottic stenosis. Each child had a history of laryngotracheal reconstruction and/or cricotracheal resection surgery. Vocal function was measured using laryngoscopy, acoustic analysis, perceptual evaluation and impact of voice on quality of life.

22q11 deletion syndrome: Parents’ and children’s experiences of educational and healthcare provision in the United Kingdom

22q11 deletion syndrome (22q11DS) is a genetic syndrome, prevalence around 1:4000–1:6000 live births, with a complex array of associated features, impacting on healthcare and educational support. This study reports the perceptions of families and individuals with 22q11DS in relation to these needs. Individuals and families of those with 22q11DS were approached though two national charities – the Max Appeal and 22Crew. An initial observational survey design was used to gather views via questions probing access to healthcare and educational experiences. Thirty-four responses were received and the data subjected to descriptive analysis. Over half of the respondents were diagnosed before the age of 1. Ninety-one percent reported ongoing difficulties with learning at school, compounded by school attendance being compromised as a result of medical interventions. Individuals reported engaging heavily with educational support and a high number of health professions (mean 9.5; mode 10). Age of diagnosis of 22q11DS ranged from birth to nine years. Families had ongoing concerns about aspects of education and healthcare services, and lack of knowledge and awareness of the difficulties faced by individuals with 22q11DS was raised. Healthcare and education providers should be aware of the range of services individuals required on a regular basis so as to provide a more holistic approach to care.