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.

Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome.

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.

Asthma education and monitoring: what has been shown to work.

Cochrane systematic reviews and meta-analyses on education and monitoring of asthmatic children have come to divergent conclusions, mainly because of the heterogeneity of education programmes and patients. There is little doubt that education is useful. However, the useful components of the education programmes remain to be elucidated, not only by randomized controlled trials but also by observational studies performed within distinct asthma phenotypes. Any education and monitoring package needs to contain basic explanation about the disease and its influencing factors, as well as inhalation instructions. There is no good evidence to justify home monitoring of lung function; symptom monitoring suffices. Probably, the crucial part of asthma education programmes is a high level of agreement between patient and doctor regarding the goals of the treatment (patient-doctor partnership). Therefore, further exploration of the patient's needs should be worthwhile.

Comparison between peak expiratory flow and FEV(1) measurements on a home spirometer and on a pneumotachograph in children with asthma.

BACKGROUND: The accuracy of electronic portable home spirometers has been demonstrated in vitro using computer-based waveforms. We assessed the agreement in vivo between measurements of lung function on an electronic spirometer (Koko Peak Pro) and those obtained by the gold standard, a hospital lung function laboratory pneumotachograph. METHODS: Fifty stable asthmatic children (33 boys), aged 6-17 years, performed peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV(1)) measurements according to international guidelines on a portable home spirometer and on the hospital pneumotachograph in random order. All measurements complied to standard quality criteria. The PEF and FEV(1) values recorded with the home spirometer and on the hospital pneumotachograph were compared. RESULTS: All children performed reproducible high-quality measurements on both spirometers. PEF values on the home spirometer were considerably lower than on the laboratory pneumotachograph (95% CI for difference in PEF 14-30 L/min; P < 0.0001). Individual differences in PEF between the two devices could be >100 L/min. The FEV(1) values were slightly, but significantly, lower on the home spirometer (95% CI for difference in FEV(1) 0.02-0.1 L; P = 0.0018). CONCLUSIONS: A home spirometer provides reproducible and quality acceptable measures in children with asthma when performed under professional supervision and encouragement. Mean PEF and FEV(1) values recorded on this home spirometer are significantly lower than those on a hospital pneumotachograph, and individual differences may be large. Therefore, home spirometry may not be interchanged with pneumotachography in a lung function laboratory.

Is home spirometry useful in diagnosing asthma in children with nonspecific respiratory symptoms?

BACKGROUND: Variation of lung function is considered to be a hallmark of asthma. Although guidelines recommend measuring it as a diagnostic tool for asthma, the usefulness of this approach has not been studied in children. AIM: To assess the usefulness of home spirometry in children with nonspecific lower respiratory tract symptoms, to diagnose or exclude asthma. METHODS: In school-aged children, referred by their general practitioner because of chronic respiratory symptoms of unknown origin, the diagnosis of asthma was made or excluded by a pediatric pulmonologist (gold standard), based on international guidelines and a standardized protocol. Additionally, children measured peak expiratory flow (PEF) and forced expiratory flow in 1 sec (FEV(1)) twice daily for 2 weeks on a home spirometer, from which diurnal variation was calculated. These results (index test) were not revealed to the pediatric pulmonologist. The value of home spirometry to diagnose asthma was calculated. RESULTS: Sixty-one children (27 boys) were included (mean age: 10.4 years; range: 6-16 years). Between asthma and no asthma, the mean difference in PEF variation was 4.4% (95% CI: 0.9-7.9; P = 0.016) and in FEV(1) variation 4.5% (95% CI: 1.6-7.4; P = 0.003). Sensitivity and specificity, based on the 95th-centile of the reference values for PEF and FEV(1) variation (12.3% and 11.8%, respectively) were 50% and 72% for PEF variation and 45% and 92% for FEV(1) variation. The likelihood ratio was 1.8 for PEF and 5.6 for FEV(1). CONCLUSIONS: The contribution of home spirometry in the diagnostic process for asthma in schoolchildren with nonspecific respiratory symptoms is limited.