Increased prevalence of sex chromosome aneuploidies in specific language impairment and dyslexia.

AIM: Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific language impairment (SLI) or dyslexia do not routinely undergo cytogenetic analysis. We assess the frequency of sex chromosome aneuploidies in individuals with language impairment or dyslexia. METHOD: Genome-wide single nucleotide polymorphism genotyping was performed in three sample sets: a clinical cohort of individuals with speech and language deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), a replication cohort of individuals with SLI, from both clinical and epidemiological samples (209 probands: 139 males, 70 females; age range 4 to 17 years), and a set of individuals with dyslexia (314 probands: 224 males, 90 females; age range 7 to 18 years). RESULTS: In the clinical language-impaired cohort, three abnormal karyotypic results were identified in probands (proband yield 3.4%). In the SLI replication cohort, six abnormalities were identified providing a consistent proband yield (2.9%). In the sample of individuals with dyslexia, two sex chromosome aneuploidies were found giving a lower proband yield of 0.6%. In total, two XYY, four XXY (Klinefelter syndrome), three XXX, one XO (Turner syndrome), and one unresolved karyotype were identified. INTERPRETATION: The frequency of sex chromosome aneuploidies within each of the three cohorts was increased over the expected population frequency (approximately 0.25%) suggesting that genetic testing may prove worthwhile for individuals with language and literacy problems and normal non-verbal IQ. Early detection of these aneuploidies can provide information and direct the appropriate management for individuals.

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 x 10(-7) at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 x 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.

Effects of computer-based intervention through acoustically modified speech (Fast ForWord) in severe mixed receptive-expressive language impairment: outcomes from a randomized controlled trial.

Seventy-seven children between the ages of 6 and 10 years, with severe mixed receptive-expressive specific language impairment (SLI), participated in a randomized controlled trial (RCT) of Fast ForWord (FFW; Scientific Learning Corporation, 1997, 2001). FFW is a computer-based intervention for treating SLI using acoustically enhanced speech stimuli. These stimuli are modified to exaggerate their time and intensity properties as part of an adaptive training process. All children who participated in the RCT maintained their regular speech and language therapy and school regime throughout the trial. Standardized measures of receptive and expressive language were used to assess performance at baseline and to measure outcome from treatment at 9 weeks and 6 months. Children were allocated to 1 of 3 groups. Group A (n = 23) received the FFW intervention as a home-based therapy for 6 weeks. Group B (n = 27) received commercially available computer-based activities designed to promote language as a control for computer games exposure. Group C (n = 27) received no additional study intervention. Each group made significant gains in language scores, but there was no additional effect for either computer intervention. Thus, the findings from this RCT do not support the efficacy of FFW as an intervention for children with severe mixed receptive-expressive SLI.

Changes in linguapalatal contact patterns during therapy for velar fronting in a 10-year-old with Down's syndrome.

BACKGROUND: Articulation errors in the speech of people with Down's syndrome are frequent and often resistant to speech therapy. This preliminary study investigates the use of electropalatography (EPG) to diagnose and treat abnormal articulation patterns associated with velar fronting in a 10-year-old girl. AIMS: The study measured changes in the accuracy and stability of linguapalatal (tongue-palate) contact patterns during a 14-week course of visual feedback therapy using EPG. Therapy aimed to resolve a pattern of velar fronting whereby targets /k, g, eta/ had alveolar placement [t, d, n]. METHODS & PROCEDURES: The participant was a girl (P) with Down's syndrome aged 10;11 years. P had a moderate-severe speech disorder, which included velar fronting. Her speech was recorded with EPG on three occasions during a 14-week course of therapy: first, before therapy; second, midway through therapy; and third, after therapy. Three analyses were conducted on the EPG data. The first used an EPG classification scheme that identified accuracy of placement for /t/ and /k/ targets. The second was a centre of gravity measure that detected whether P produced a significant difference between /t/ and /k/ targets. The third was a variability index that quantified the stability of contact patterns. OUTCOMES & RESULTS: The results of the EPG classification showed that before therapy, /t/ and /k/ targets had identical alveolar placement, reflecting the process of velar fronting. The results after therapy showed that 87% of /k/ targets had accurate velar placement. The centre of gravity measure showed no difference in contact patterns for /t/ and /k/ before therapy, but a statistically significant difference at the second and third recordings. The variability index showed stable contact patterns before therapy for /t/ and /k/ targets, but both became highly unstable midway through therapy, with a return to stability at the third recording. We embed a discussion of P's increased articulation instability during therapy in a recent theoretical framework--dynamic systems--that attempts to account for the emergence of new behavioural forms. CONCLUSIONS: These preliminary results suggest that EPG has potential as an effective diagnostic and therapy procedure for articulation errors in people with Down's syndrome. A major issue still to be addressed, however, is the extent to which others will benefit from this approach to intervention.