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

Médicalisation préhospitalière héliportée et agressions cérébrales secondaires d'origine systémique chez les traumatisés craniocérébraux graves [Prehospital air ambulance and systemic secondary cerebral damage in severe craniocerebral injuries]

Advanced supportive therapy at the site of the accident, associated with direct transfer to a trauma centre increases survival and reduces morbidity rates. Patients with severe head injury, especially those with multiple injuries, often arrive in the emergency department with potentially causes of serious secondary systemic insults to the already injured brain, such as acute anemia (Hematocrit &lt; or = 30%), hypotension (systolic arterial pressure (Pasys) &lt; or = 95 mmHg, 12.7 kPa), hypercapnia (Paco2 &gt; or = 45 mmHg, 6 kPa) and/or hypoxemia (Pao2 &lt; or = 65 mmHg, 8.7 kPa). The incidence of such insults and their impact on mortality were studied in a group of 51 consecutive adults suffering from non penetrating severe head injury (Glasgow score &lt; or = 8, mean age 31 +/- 17 yrs) rescued by a medicalized helicopter. Each patient received medical care on the site of the accident by an anaesthesiologist of a university hospital (UH) complying with an advanced trauma life support protocol including intubation, hyperventilation with FiO2 = 1, restoration of an adequate Pasys and direct transportation to the UH. Mean delay from call to arrival of the rescue team on the site was 15 +/- 5 min. Mean scene time was 32 +/- 10 min in cases not requiring extrication. Nineteen patients (Group I) were admitted without secondary systemic insults to the brain, 13 with isolated head injury, and 6 with multiple injuries, with a low Glasgow Outcome Score (GOS 1-3) of 42% at 3 months. In 32 patients (Group II), despite advanced supportive measures at the scene of the accident and during transportation, one or more secondary systemic insults to the brain were detected upon arrival at the emergency room, one with isolated head injury, 31 with multiple injuries, with a bad GOS of 72% at 3 months. We conclude that: 1) advanced trauma life support prevents from secondary systemic insults in the great majority of isolated severe head injured patients. 2) secondary systemic insults to the already injured brain are frequent in patients with multiple injuries and are difficult to avoid despite rapid aeromedical trauma care, 3) secondary systemic insults to the brain have a catastrophic impact on the outcome of severely head injured patients

Hémodynamique cérébrale et hypertensions intracrâniennes [Cerebral hemodynamics and intracranial hypertension]

Various cerebral aggressions, either primary or secondary, can lead to the development of raised intracranial pressure. The presence of an elevated intracranial pressure often results in cerebral ischaemia/hypoxia and, eventually, neuronal death. In face of this cascade of events, several therapeutic approaches have been suggested. Two management concepts for patients with raised intracranial pressure have retained the most attention in recent years: the first suggests a therapeutic increase in cerebral perfusion pressure with the objectives to improve perilesional collateral perfusion and decreased cerebral blood volume, and consequently intracranial pressure in areas where autoregulation is preserved. The second concept supports the diminution in perilesional capillary pressure with the aim of decreasing vasogenic oedema. Although these two concepts are antagonistic and cannot be used simultaneously, they are probably complementary in the sequence of therapeutic events of patients experiencing severe head injury. This article reviews these therapeutic concepts and their clinical applications

Additional Efnb1 Mutations In Craniofrontonasal Syndrome

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