Kristine Stadskleiv

A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform

Import of peroxisomal matrix proteins, crucial for peroxisome biogenesis, is mediated by the cytosolic receptors PEX5 and PEX7 that recognize proteins carrying peroxisomal targeting signals 1 or 2 (PTS1 or PTS2), respectively. Mutations in PEX5 or 12 other PEX genes cause peroxisome biogenesis disorders, collectively named the Zellweger spectrum disorders (ZSDs), whereas mutations in PEX7 cause rhizomelic chondrodysplasia punctata type 1 (RCDP1). Three additional RCDP types, RCDP2-3-4, are caused, respectively, by mutations in GNPAT, AGPS and FAR1, encoding enzymes involved in plasmalogen biosynthesis. Here we report a fifth type of RCDP (RCDP5) caused by a novel mutation in PEX5. In four patients with RCDP from two independent families, we identified a homozygous frame shift mutation c.722dupA (p.Val242Glyfs(∗)33) in PEX5 (GenBank: NM_001131023.1). PEX5 encodes two isoforms, PEX5L and PEX5S, and we show that the c.722dupA mutation, located in the PEX5L-specific exon 9, results in loss of PEX5L only. Both PEX5 isoforms recognize PTS1-tagged proteins, but PEX5L is also a co-receptor for PTS2-tagged proteins. Previous patients with PEX5 mutations had ZSD, mainly due to deficient import of PTS1-tagged proteins. Similarly to mutations in PEX7, loss of PEX5L results in deficient import of PTS2-tagged proteins only, thus causing RCDP instead of ZSD. We demonstrate that PEX5L expression restores the import of PTS2-tagged proteins in patient fibroblasts. Due to the biochemical overlap between RCDP1 and RCDP5, sequencing of PEX7 and exon 9 in PEX5 should be performed in patients with a selective defect in the import of PTS2-tagged proteins.

Investigating executive functions in children with severe speech and movement disorders using structured tasks

Executive functions are the basis for goal-directed activity and include planning, monitoring, and inhibition, and language seems to play a role in the development of these functions. There is a tradition of studying executive function in both typical and atypical populations, and the present study investigates executive functions in children with severe speech and motor impairments who are communicating using communication aids with graphic symbols, letters, and/or words. There are few neuropsychological studies of children in this group and little is known about their cognitive functioning, including executive functions. It was hypothesized that aided communication would tax executive functions more than speech. Twenty-nine children using communication aids and 27 naturally speaking children participated. Structured tasks resembling everyday activities, where the action goals had to be reached through communication with a partner, were used to get information about executive functions. The children (a) directed the partner to perform actions like building a Lego tower from a model the partner could not see and (b) gave information about an object without naming it to a person who had to guess what object it was. The executive functions of planning, monitoring, and impulse control were coded from the childrens on-task behavior. Both groups solved most of the tasks correctly, indicating that aided communicators are able to use language to direct another person to do a complex set of actions. Planning and lack of impulsivity was positively related to task success in both groups. The aided group completed significantly fewer tasks, spent longer time and showed more variation in performance than the comparison group. The aided communicators scored lower on planning and showed more impulsivity than the comparison group, while both groups showed an equal degree of monitoring of the work progress. The results are consistent with the hypothesis that aided language tax executive functions more than speech. The results may also indicate that aided communicators have less experience with these kinds of play activities. The findings broaden the perspective on executive functions and have implications for interventions for motor-impaired children developing aided communication.

Assessment of verbal comprehension and non-verbal reasoning when standard response mode is challenging: A comparison of different response modes and an exploration of their clinical usefulness

Abstract Objective: Assessment of cognition is important for providing children with developmentally appropriate interventions. Often children with severe speech and motor disorders are not assessed, as standardized assessment is perceived as challenging. This study investigates how assessments of cognition can be conducted using alternative response modes. Method: The study has two parts. The response modes finger pointing (FP), gaze pointing (GP), and partner-assisted scanning (PAS) were compared when assessing verbal comprehension and visuospatial abilities in 27 typically developing (TD) children, aged 5; 10–6; 10 years. Clinical utility was investigated by assessing 69 children with cerebral palsy (CP), using FP or GP as response mode depending on motor functioning. Results: In TD first graders, using alternative response modes did not influence the test results (Wilks’s lambda = 0.871, F (2, 23) = 1.70, p = 0.204). PAS was more time consuming than FP and GP on some of the tasks. In the CP group, considerable individual variation was found both when using FP (standard scores 40–138) and GP (37–120). Conclusions: Type of response mode did not impact test results in typically developing children. Assessment of cognition is possible even when children have severe speech and movement impairments.

Children Who Use Communication Aids Instructing Peer and Adult Partners During Play-Based Activity

Abstract Little is known about how children with severe motor impairments who use communication aids provide instructions when given control over interaction. In this study, 35 children – 18 who used communication aids and 17 who used natural speech – were videotaped in play-based activities. Both groups successfully instructed partners to build replications of models the partners could not see. The results demonstrate that children using communication aids can also have an active role in play-based activities using language, but that their experience with activities may be limited and their instructions may take longer to give. The children who used natural speech provided more detailed instructions and were more successful in guiding their partners. Creating opportunities for active participation in play may be important for the development of communicative autonomy.

Systematic cognitive monitoring of children with cerebral palsy – the development of an assessment and follow-up protocol

ABSTRACTCerebral palsy (CP) is associated with cognitive impairments, learning difficulties and reduced social participation. Individual assessment is necessary for individually tailored interventions. This paper describes the development of a systematic follow-up programme of cognition, and the challenges of integrating it into the regular follow-up of children with CP. Initiated by the Nordic users‘ organisations, a group of psychologists proposed a protocol of follow-up of cognition in children with CP – the CP Cog. This protocol consists of neuropsychological instruments covering general cognitive functioning, visuospatial and executive functioning. The article presents a natural experiment describing development and implementation of the cognitive protocol in three Scandinavian countries. This introduction illustrates challenges associated with implementation, especially how the success of the protocol hinges on structural backup within the different countries. In conclusion the CP Cog assessment pro...

Neuropsychological profiles of children with cerebral palsy

ABSTRACT Purpose: To explore factors contributing to variability in cognitive functioning in children with cerebral palsy (CP). Method: A geographical cohort of 70 children with CP was assessed with tests of language comprehension, visual-spatial reasoning, attention, working memory, memory, and executive functioning. Mean age was 9;9 years (range 5;1–17;7), 54.3% were girls, and 50.0% had hemiplegic, 25.7% diplegic, 12.9% quadriplegic, and 11.4% dyskinetic CP. For the participants with severe motor impairments, assessments were adapted for gaze pointing. A cognitive quotient (CQ) was computed. Results: Mean CQ was 78.5 (range 19–123). Gross motor functioning, epilepsy, and type of brain injury explained 35.5% of the variance in CQ (F = 10.643, p = .000). Conclusion: Twenty-four percent had an intellectual disability, most of them were children with quadriplegic CP. Verbal comprehension and perceptual reasoning scores did only differ for the 21% with an uneven profile, of whom two-thirds had challenges with perceptual reasoning.

Vocabulary comprehension and strategies in name construction among children using aided communication

Abstract Vocabulary learning reflects the language experiences of the child, both in typical and atypical development, although the vocabulary development of children who use aided communication may differ from children who use natural speech. This study compared the performance of children using aided communication with that of peers using natural speech on two measures of vocabulary knowledge: comprehension of graphic symbols and labeling of common objects. There were 92 participants not considered intellectually disabled in the aided group. The reference group consisted of 60 participants without known disorders. The comprehension task consisted of 63 items presented individually in each participant’s graphic system, together with four colored line drawings. Participants were required to indicate which drawing corresponded to the symbol. In the expressive labelling task, 20 common objects presented in drawings had to be named. Both groups indicated the correct drawing for most of the items in the comprehension tasks, with a small advantage for the reference group. The reference group named most objects quickly and accurately, demonstrating that the objects were common and easily named. The aided language group named the majority correctly and in addition used a variety of naming strategies; they required more time than the reference group. The results give insights into lexical processing in aided communication and may have implications for aided language intervention.

Assessment of aided language comprehension and use in children and adolescents with severe speech and motor impairments

Abstract There is limited knowledge about aided language comprehension and use in children who use aided communication and who are considered to have a relatively good comprehension of spoken language. This study’s purpose was to assess their aided language skills. The participants were 96 children and adolescents who used communication aids (aided group) and 73 children and adolescents with natural speech (reference group), aged 5 to 15 years. All of the participants who used aided communication were regarded by their teachers or professionals as having age-appropriate language comprehension. All of the participants completed (a) standardized tests of visual perception, non-verbal reasoning, and comprehension of spoken language, and (b) tasks designed for this study that measured comprehension and production of graphic utterances through communicative problem solving. Using their own communication systems, the participants achieved an average of 72% correct on the graphic symbol comprehension task items, and 63% on the expressive tasks. The participants with natural speech achieved an average of 88% correct on comprehension items, and 93–96% accuracy on production items. The differences between groups were significant on all the tasks and standardized tests. There was considerable variation within the group of participants who used aided communication, and the results reveal a need to develop instruments with norms for aided language competence that can inform the implementation of interventions to support aided language development.

Communicating the unknown: descriptions of pictured scenes and events presented on video by children and adolescents using aided communication and their peers using natural speech

Abstract The facility to describe scenes and events is important in everyday communication, but little is known about the description skills and strategies of young people using aided communication. This article explores how 81 children and adolescents using aided communication and 56 peers using natural speech, aged 5–15 years, described pictured scenes and events presented on video to a partner who had no prior knowledge of the content. The group who used aided communication took longer and included fewer elements in their descriptions than the reference group; however, the groups did not differ in their use of irrelevant or incorrect elements, suggesting that both groups stayed on topic. Measures related to aided message efficiency correlated significantly with measures of spoken language comprehension. There were no significant differences between groups for their descriptions of pictured scenes and video events. Analyses showed both unpredicted group similarities and predictable differences, suggesting key components for future research consideration.

Visual-spatial cognition in children using aided communication

Abstract Children with severe motor impairments are restricted in their manipulation and exploration of objects, but little is known about how such limitations influence cognitive development. This study investigated visual-constructional abilities in 75 children and adolescents, aged 5;0–15;11 (years;months), with severe speech impairments and no intellectual disabilities (aided group) and in 56 children and adolescents with typical development (reference group). Verbal comprehension, non-verbal reasoning, and visual-spatial perception were assessed with standardized tests. The task of the participants was to verbally instruct communication partners to make physical constructions identical to models that the partner could not see. In the aided group, 55.7% of the constructions were identical to the models participants described, compared to 91.3% in the reference group. In the aided group, test results explained 51.4% of the variance in construction errors. The results indicate that the participants’ language skills were decisive for construction success. Visual-perceptual challenges were common among the aided communicators, and their instructions included little information about size and spatial relations. This may reflect less experience with object manipulation and construction than children with typical development, and using aided communication to instruct others to make three-dimensional constructions. The results imply a need for interventions that compensate for the lack of relevant experience.