The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Goal Attainment Scaling in paediatric rehabilitation practice : a useful outcome measure

The main aim of this thesis was to investigate the use of a 6-point Goal Attainment Scaling (GAS) system to measure change over time in interdisciplinary rehabilitation practice for children with Cerebral Palsy (CP). GAS is a generic individualized evaluative criterion-referenced instrument. It can be used for measurement of changes in activities and participation in individual patients and in groups of patients. First a study to measure the effect of Botulinum Toxin A treatment was performed using GAS. A single-blind randomized multiple baseline/treatment phase study across subjects was used for 33 goals of 11 children with CP. Each goal was recorded weekly with a standard video for a period of 14 weeks. Rating of pre-determined GAS scales was performed blinded. This study showed that GAS could demonstrate clinically relevant improvement in individual rehabilitation goals. Second, a critical review of the literature about the content reliability, inter-rater reliability, validity, sensitivity to change of GAS and its use in paediatric rehabilitation research was performed. The review showed that current knowledge about its reliability, when used with children, was insufficient. Moreover, its added value and responsiveness should be explored more specifically. This resulted in the next project which was performed on the clinimetric properties of GAS. We started by developing a training program for physical, occupational, speech-language therapists, paediatric psychologists and social workers. We determined criteria for GAS scales: they should be ordinal, describe specific, measurable, acceptable, realistic abilities, activities or participation in a single dimension, use the ‘can-do’ principle and it should be possible to score them within 10 minutes. Therapists and parents regarded GAS as a suitable tool to improve the quality of rehabilitation treatment. The first issue we investigated was the inter-rater reliability. A reliability study was performed in which 23 children with CP and 20 trained therapists of 3 disciplines were enrolled. The child’s own therapists, and for each therapist an independent therapist from the same discipline, constructed 64 GAS scales each. They scored both their own scale and their partner’s scale resulting in 128 scores. The inter-rater reliability of GAS was good. The results also suggested that scale construction by the child’s own therapist as opposed to an independent rater has a positive influence on the inter-rater reliability of the scales. This finding was reassuring regarding the phenomenon of “therapist bias”. Finally, the content of GAS scales was compared to the PEDI and GMFM-66 using the ICF-CY. The instruments were complementary in construct and individual responsiveness. A substantial number of achieved goals could have been missed if only standardized measures were used, even if the ICF-item of the rehabilitation goal matched the items of these measures. Moreover, by using GAS alone, small changes could have been missed. Positive attributes of GAS include quantifying the relevance of the change measured, the comparability of goal attainment across goals and individuals, and the ability to measure progress that would otherwise not have been measured. Issues regarding GAS include reservations about the content validity related to the professional insight

The effect of botulinum toxin type A treatment of the lower extremity on the level of functional abilities in children with cerebral palsy: evaluation with goal attainment scaling

OBJECTIVE: To measure the effect of botulinum toxin type A (BTX-A) treatment in children with cerebral palsy with regard to individual goals concerning functional abilities, using goal attainment scaling. DESIGN: A single-blind randomized multiple baseline/treatment phase design across subjects. SETTING: The paediatric department of a rehabilitation centre. SUBJECTS: Eleven children with cerebral palsy participated. INTERVENTION: BTX-A treatment of the lower extremity. MAIN MEASURES: A six-point goal attainment scaling of three individual treatment goals at the level of functional abilities. Standardized video-tapes of each goal were recorded weekly for a period of 14 weeks. Rating on the predetermined goal attainment scaling was blinded. RESULTS: Nine of the 11 subjects showed significant improvement in 18 out of 33 goals. Seven subjects showed clinically relevant improvement (at least 2 points on the goal attainment scaling) in 11 goals. Testing the difference between all medians of baseline measurements (after correction for improvement during baseline) and the medians of the treatment phase measurements for all goal attainment scaling scores (n = 33) resulted in significant improvement (p <0.001). Tested at subject level (medians of the three goal attainment scaling scores per assessment, n = 11), a significant improvement was also found (p = 0.005). The change in goal attainment scaling score was related to the moment of treatment with BTX-A. CONCLUSION: Clinically relevant improvement in individual rehabilitation goals at ability level, achieved with the treatment of BTX-A in children with cerebral palsy, were demonstrated using the goal attainment scaling metho

Supplementary_Material – Supplemental material for Hand-Use-at-Home Questionnaire: validity and reliability in children with neonatal brachial plexus palsy or unilateral cerebral palsy

<p>Supplemental material, Supplementary_Material for Hand-Use-at-Home Questionnaire: validity and reliability in children with neonatal brachial plexus palsy or unilateral cerebral palsy by Menno van der Holst, Yvonne Geerdink, Pauline Aarts, Duco Steenbeek, Willem Pondaag, Rob GHH Nelissen, Alexander CH Geurts and Thea PM Vliet Vlieland in Clinical Rehabilitation</p

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The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features