Severe Developmental Language Disorders Research Articles

Whole exome sequencing and polygenic assessment of a Swedish cohort with severe developmental language disorder

Developmental language disorder (DLD) overlaps clinically, genetically, and pathologically with other neurodevelopmental disorders (NDD), corroborating the concept of the NDD continuum. There is a lack of studies to understand the whole genetic spectrum in individuals with DLD. Previously, we recruited 61 probands with severe DLD from 59 families and examined 59 of them and their families using microarray genotyping with a 6.8% diagnostic yield. Herein, we investigated 53 of those probands using whole exome sequencing (WES). Additionally, we used polygenic risk scores (PRS) to understand the within family enrichment of neurodevelopmental difficulties and examine the associations between the results of language-related tests in the probands and language-related PRS. We identified clinically significant variants in four probands, resulting in a 7.5% (4/53) molecular diagnostic yield. Those variants were in PAK2, MED13, PLCB4, and TNRC6B. We also prioritized additional variants for future studies for their role in DLD, including high-impact variants in PARD3 and DIP2C. PRS did not explain the aggregation of neurodevelopmental difficulties in these families. We did not detect significant associations between the language-related tests and language-related PRS. Our results support using WES as the first-tier genetic test for DLD as it can identify monogenic DLD forms. Large-scale sequencing studies for DLD are needed to identify new genes and investigate the polygenic contribution to the condition.

Why Clinicians Choose Their Language Intervention Approach: An International Perspective on Intervention for Children with Developmental Language Disorder

Purpose: Considerable progress has been made in recent years in generating external evidence underpinning interventions for children with developmental language disorder (DLD), but less is known about the practitioner decision-making process underpinning such interventions and whether such decisions are context specific or are internationally generalizable. Methods: An online survey about clinical practice was developed by members of COST Action IS1406, an EU-funded research network, which included representation from 39 countries. The participants were 2,408 practitioners who answered questions in relation to their decision making for a specific child of their choosing with DLD. Analysis of open-ended questions was undertaken, and data were converted into codes for the purpose of quantitative analysis. Results: Although a wide range of intervention approaches and rationales were reported, the majority of responses referenced a client-centred approach. Level of functioning was used as a rationale only if a child had severe DLD. Practitioners with university level education or above were less likely to report basing intervention on client-centred factors. A number of differently named interventions with variable theoretical and empirical underpinnings were used in different countries. Conclusions: Specific client and practitioner characteristics have an impact on the intervention approaches and rationales adopted across countries. A limited number of practitioners reported use of external scientific evidence, which suggests that there should be more initiatives in basic training of practitioners and continuing professional development to encourage the uptake of scientific evidence-based practice.

Phonological and orthographic reading routes in French-speaking children with severe developmental language disorder

PurposeThis study aims to assess written word recognition in French-speaking children with severe developmental language disorder (DLD), using a task of reading in silence. The objective is to determine if the balance between the phonological reading route and the orthographic route of these children is similar to that of typically developing children, on the basis of the so-called “dual route” model. MethodA visual lexical decision task was used in 19 children with severe DLD (average age: 11.01 years), 19 control children of the same reading level (RC children, average age: 8.12 years), and 19 children of the same chronological age (AC children, average age: 10.84 years). This task included words and pseudowords associated with these words: pseudohomophones, pseudowords phonologically close but visually distant to the true words, visually close but phonologically distant pseudowords. ResultsThe groups did not process the pseudowords in the same way. Children with severe DLD were more successful than RC children for pseudohomophones. They tended to be less successful for phonologically close and visually distant pseudowords. They were similarly successful for visually close and phonologically distant pseudowords. Children with severe DLD were less successful than AC children with each type of pseudowords. ConclusionsThese results suggest that children with severe DLD do not simply present a homogeneous delay in their ability to recognize written words but rather a deviant development compared to RC children, with a stronger reliance on the orthographic reading route compared to the phonological one. It is likely that the phonological difficulties of children with severe DLD have hindered the development of their phonological reading route which, in turn, have hindered the development of their orthographic route.

Enrichment of rare copy number variation in children with developmental language disorder.

Developmental language disorder (DLD) is a common neurodevelopmental disorder with largely unknown etiology. Rare copy number variants (CNVs) have been implicated in the genetic architecture of other neurodevelopmental disorders (NDDs), which have led to clinical genetic testing recommendations for these disorders; however, the evidence is still lacking for DLD. We analyzed rare and de novo CNVs in 58 probands with severe DLD, their 159 family members and 76 Swedish typically developing children using high-resolution microarray. DLD probands had larger rare CNVs as measured by total length (P = .05), and average length (P = .04). In addition, the rate of rare CNVs overlapping coding genes was increased (P = .03 and P = .01) and in average more genes were affected (P = .006 and P = .03) in the probands and their siblings, respectively. De novo CNVs were found in 4.8% DLD probands (2/42) and 2.4% (1/42) siblings. Clinically significant CNVs or chromosomal anomalies were found in 6.9% (4/58) of the probands of which 2 carried 16p11.2 deletions. We provide further evidence that rare CNVs contribute to the etiology of DLD in loci that overlap with other NDDs. Based on our results and earlier literature, families with DLD should be offered molecular genetic testing as a routine in their clinical follow-up.

Quality of life in children with developmental language disorder.

Developmental language disorder (DLD) is common in children, but little is known about its association with quality of life (QoL) in middle childhood. QoL is a complex construct, aligning with an individual's sense of well-being and is related to functional limitations associated with DLD. Biopsychosocial models of disability account for both the extent and functional limitations of the impairment; however, the DLD literature rarely reports on both aspects. Studies are required that detail QoL in children with and without DLD. To investigate the association between DLD, identified at 4 years and persisting at 7 years, and QoL over 4, 7 and 9 years; to compare QoL for children whose DLD was mild to moderate and severe at 7 years; and to investigate how variables known to impact on language development (e.g., maternal vocabulary), as well as social-emotional behaviours at 4 and 7 years contribute to QoL at 9 years. The analyses included 872 children who participated in the 4-, 7- and 9-year data collection of the Early Language in Victoria Study (ELVS). We compared the parent-reported QoL profiles at 4, 7 and 9 years for children with and without DLD, and those with mild to moderate and severe DLD using the Pediatric Quality of Life Inventory (PedsQL). We conducted regression analyses to estimate how child, family and environmental factors predicted QoL at 9 years, including social-emotional behaviours measured using the Strengths & Difficulties Questionnaire (SDQ) at 4 and 7 years. Children with DLD (n = 70) had lower parent-reported QoL at 9 years than typically developing children (n = 802), with mean scores of 74.9 and 83.9 respectively. There was no evidence of differences in QoL between those with severe (n = 14) or mild to moderate (n = 56) DLD. In contrast to their peers, children with DLD had a profile of declining QoL between 4 and 9 years. For all children, language skills at 7 years predicted QoL at 9 years. For children with DLD, emotional symptoms and peer problems at 4 years plus SDQ Total Difficulties at 7 years were predictive of lower QoL at 9 years. Children with DLD had a lower QoL than their typical peers at 9 years and, contrary to previous studies, differences in QoL were not observed with DLD severity. Co-occurring social-emotional problems appear to play an important role in contributing to the lower QoL experienced by children with DLD. Consideration of associated functional limitations is required to support the communication and social development of all young children with DLD.

Comorbidity in severe developmental language disorders: Neuropediatric and psychological considerations

To explore possible patterns of comorbidity in children with severe developmental language disorders (DLD). A retrospective investigation of the clinical records of 28 children relating to oral motor and language problems, psychological profiles, medical history and EEG findings. 36% of all the children had pure expressive language problems, 64% had combined expressive-receptive language problems and 57% had additional oral motor problems. Girls predominated in expressive-receptive problems, while boys predominated in oral motor problems. Children with expressive-receptive disorders were over-represented at the lower end of normal full-scale IQ (p = 0.015). Lower verbal than non-verbal IQ levels were almost as common as equal levels, but a lower non-verbal IQ than verbal IQ was also found. Pre/perinatal problems were found in 21%, and heredity for developmental language problems or dyslexia in 39%. There was a higher proportion of attention and motor problems, EEG abnormalities, and epileptic syndromes than in the general population (p < 0.001). In severe DLD, both pure expressive and mixed expressive-receptive problems are found, and oral motor problems are common. Gender differences regarding symptoms are present. Receptive language ability is associated with the full-scale IQ level. A high proportion of EEG abnormalities and epilepsy is found. There is a complex pattern of comorbidity between speech-language symptoms, psychological characteristics, heredity and EEG findings.

Comorbidity in severe developmental language disorders: Neuropediatric and psychological considerations

To determine the concentration of vitamin K including K1 (phylloquinone) and K2 (menaquinone-n; MK-n) in the maternal milk of Japanese women. We collected human milk samples from more than 4000 mothers living throughout Japan from December 1998 to September 1999, and analysed the contents of vitamin K1 and K2 in 834 of the samples. We defined as group A the 555 samples among them that met the following conditions: breast milk of mothers who were under 40 y old, not in the habit of smoking and/or using vitamin supplements, and whose babies showed no symptoms of atopy and whose birthweights were 2.5 kg or more. Vitamins extracted from the enzymatic hydrolysates of the human milk were purified with a Sep-Pak Plus silica cartridge, and then measured by a method based on high-performance liquid chromatography (HPLC) combined with coulometric reduction and fluorometric detection. The mean concentration of vitamin K (K1 + K2) of mothers of group A and all groups were 0.434 +/- 0.293 and 0.517 +/- 1.521 microg/100 ml (average +/- SD), respectively, and menaquinones containing 4, 6 and 7 isoprenoid residues could be detected in the milk samples. Vitamins K1 and MK-4 were found to be predominant in the milk samples, and the concentration of MK-4 in colostrum was higher than that of MK-4 in mature milk. We also found that the MK-7 concentration in the milk of mothers living in eastern Japan was higher than that of mothers living in western Japan. The different features of vitamin K1 and MK-7 concentrations in the milk of Japanese women may be due to differences in dietary foods.

Children with severe language disorder six years later: A follow-up study from language preschool to grade 4 and 5

Nine children with specific and severe developmental language disorder (DLD) were assessed on language, reading and spelling tasks in grades four and five. The DLD children had earlier attended a language preschool program. Four children performed within normal limits on a standardized reading test but only one child reached a normal performance on a spelling test. The best readers and spellers in the group were the most proficient on semantic measures in the present investigation and in preschool. Their language production (phonology and grammar) at age 5 was also more developed than in the other children (with one exception). Our results further strengthens the concept of “hierarchical vulnerability of language” in children (Bishop and Edmundsson, 1987).

A longitudinal study of ten children with severe developmental language disorders

On the basis of a neurolinguistic assessment procedure (Holmberg and Sahlen, 1986) ten children with severe and specific developmental language disorders (DLD) were studied over a four-year period. Initially they all showed global language problems which, in the course of development, became more specific. Although there were considerable differences in the neurolinguistic profiles, some general patterns were hypothesized. The linguistic analysis revealed some speech production correlates to these patterns. The results of the segmental phonological analysis and the grammatical analysis, however, did not reflect the differences between the neurolinguistic patterns. We argue that other, more dynamic aspects of language production, i.e. sentence prosody and speech rate, may better discriminate between children with different neurolinguistic patterns. A process-oriented approach to grammatical error analysis and the concept of linguistic levels are discussed.

Patterns of vulnerability of language in children with severe developmental language disorders

Language disordered children with receptive language problems have worse outcome and also more severe problems in other areas of language than children with isolated expressive problems according to “the hypothesis of hierarchical vulnerability” formulated by Bishop and Edmundson (1987). We studied ten children with specific and severe developmental language disorders (DLD) longitudinally and found that the hypothesis was tenable with regard to the predictions about outcome. We also found that among children in the phonologic-syntactic subgroup (Rapin and Allen, 1983), children with poor comprehension and poor lexical-semantic ability had the most severe problems of syntax. Phonological production at ages 5 or 6 was not correlated to phonological production at age 8. Oral motor function, however, turned out to be an important prognostic factor for phonological outcome. The present findings call for revised methodological routines and therapeutical priorities regarding children with severe DLD.

Severe developmental language disorder ? Reading and spelling

Linguistic awareness i.e. the ability to identify phonemes, to segment words into syllables and to rhyme is highly correlated with reading/spelling proficiency. Children with severe developmental language disorders DLD (syntagmatic type) have been shown to specifically lack linguistic awareness. Two non-identical twin boys with severe, specific DLD were studied longitudinally with respect to their linguistic, neurolinguistic and pragmatic development. In spite of poor linguistic awareness, the boys acquired normal reading/spelling skills. This might be due to the early and massive language training they were given. However, the boys differ considerably in some aspects of reading and spelling performance. These findings are discussed with reference to their different neurolinguistic and pragmatic profiles.

Language Disorders in Children Referred for Psychiatric Services

Surveys of language-impaired children at speech and hearing clinics invariably show a high frequency of psychiatric disorders. However, there have been few investigations of the frequency of developmental language disorders in children referred for psychiatric services, although the presence of such a disorder would clearly be expected to influence diagnosis and treatment. In this survey of 40 consecutive admissions to a child psychiatry inpatient service, at least half of the children had moderate to severe developmental language disorders. The disorders were found in children with a wide variety of psychiatric diagnoses, and routine intellectual testing did not invariably detect the presence of developmental dysphasia. Recommendations for screening, diagnosis and treatment of language-disordered children with psychiatric problems are given.

A study of language development in a sample of 3 year old children.

A small study was set up to investigate the prevalence of delayed language development in an urban sample of 3 year old children. Verbal comprehension, expressive language, articulation and intelligibility were assessed. Children from immigrant families performed particularly poorly on the assessment scales, and were not included in the subsequent analysis. In the remaining sample of 160 children, no child was found to have a severe developmental language disorder, and only one with a significant specific language delay which was still present at the age of 4 years. The sample was too small for a study of the prevalence of severe developmental language disorder, but some interesting suggestions emerged in relation to the effects of social grade, size of family and attendance at nursery school. Good language performance seemed to be related to a complex of high social grade, small family, and attendance at nursery school.