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

Risk of malignancy in 22q11.2 deletion syndrome

22q11.2DS is a significant health problem because of its fairly high incidence. It is relevant to be vigilant regarding the diagnosis of cancer amongst 22q11.2 patients as there might be an increased risk, especially amongst patients with the 22q11.2 distal deletion syndrome

Exploring the role of non-coding variation in hereditary blindness : Stargardt disease as a model

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Prise en charge de l'achondroplasie en Belgique : Aperçu de la pratique actuelle sur base d'une enquête multicentrique.

peer reviewedAchondroplasia (ACH), one of the most common skeletal dysplasia is a multisystem disorder with a range of complications leading to reduced quality of life. In 2022, an international consensus statement was published with guidelines for ACH management and care. This prompted us to collect data on the current management policy of ACH paediatric patients in Belgium. Materials and Methods Data from 6 Belgian centres were collected in 2022 through the completion of a survey by minimum one ACH expert (N=9) from each centre. The survey focused on the time of diagnosis, the composition of the multidisciplinary team (MDT), the follow-up schedule and the main paediatric complications. Results The 6 centres reported a total of 94 patients being followed up. In each MDT a clinical geneticist and an orthopaedic surgeon are involved (N=9/9). Paediatric endocrinologists, neuropaediatricians, and ENT physicians are the most frequently associated members (N=8/9). Most ACH cases (70-100%) are diagnosed prenatally (N=7/7). During the follow-up, ACHadapted developmental tools and growth charts are systematically used (N=9/9). In all centres, screening for foramen magnum stenosis (FMS) between the ages 0 - 2 years is only performed when clinically indicated. Polysomnography is performed at least once before the first birthday in 5/6 centres. A frequency scale question to the experts (n=9) was used to estimate the occurrences of the complications in this cohort. Recurrent otitis media is the most frequent reported complication (N=7/9). FMS requiring decompression surgery is mentioned as rarely performed (N=5/9) and limb lengthening surgery seems to be restricted to a few centres (N=3/8). Conclusions The survey highlights the variability in care management of ACH amongst the di[erent centres, illustrating the need for a national consensus protocol. Additionally, data collection in the field of rare diseases such as ACH remains challenging and underlines the need of accurate registries, especially with the perspective of new therapeutic modalities