Correlation between Phenotype and Genotype in CTNNB1 Syndrome: A Systematic Review of the Literature.

The CTNNB1 Syndrome is a rare neurodevelopmental disorder associated with developmental delay, intellectual disability, and delayed or absent speech. The aim of the present study is to systematically review the available data on the prevalence of clinical manifestations and to evaluate the correlation between phenotype and genotype in published cases of patients with CTNNB1 Syndrome. Studies were identified by systematic searches of four major databases. Information was collected on patients' genetic mutations, prenatal and neonatal problems, head circumference, muscle tone, EEG and MRI results, dysmorphic features, eye abnormalities, early development, language and comprehension, behavioral characteristics, and additional clinical problems. In addition, the mutations were classified into five groups according to the severity of symptoms. The study showed wide genotypic and phenotypic variability in patients with CTNNB1 Syndrome. The most common moderate-severe phenotype manifested in facial dysmorphisms, microcephaly, various motor disabilities, language and cognitive impairments, and behavioral abnormalities (e.g., autistic-like or aggressive behavior). Nonsense and missense mutations occurring in exons 14 and 15 were classified in the normal clinical outcome category/group because they had presented an otherwise normal phenotype, except for eye abnormalities. A milder phenotype was also observed with missense and nonsense mutations in exon 13. The autosomal dominant CTNNB1 Syndrome encompasses a wide spectrum of clinical features, ranging from normal to severe. While mutations cannot be more generally categorized by location, it is generally observed that the C-terminal protein region (exons 13, 14, 15) correlates with a milder phenotype.

Clinical outcomes of reperfusion therapy in patients with site-specific basilar artery occlusion.

BACKGROUND: Despite its low incidence, basilar artery occlusion (BAO) remains a major therapeutic challenge since severe disability and death occur in about 80% of patients. Specific site of BAO (proximal, middle, or distal) has rarely been reported as a prognostic factor in reperfusion therapy. We aimed to explore the relationship between site-specific BAO and clinical outcomes in patients treated with reperfusion therapies. METHODS: We performed a single-centre retrospective study of all consecutive patients with acute BAO admitted to the University Medical Centre Ljubljana between January 2013 and August 2022 who were treated with reperfusion therapies. Patients were grouped according to the location of BAO and compared for baseline characteristics, differences in stroke aetiology, type of reperfusion therapy, success of recanalization, and clinical outcome after 90 days evaluated by the modified Rankin Scale (mRS) score. Statistical analysis was performed with the two-sided ANOVA t-tests for continuous measures, Chi-squared (χ2) tests for categorical measures and a multivariate ordinal logistic regression analysis. RESULTS: The study included 103 patients (47% females, median age 74 years; confidence interval (CI) 72 to 98). Proximal BAO was found in 13%, middle in 13%, and distal in 74% of patients. Cardioembolic etiology was more common in distal (=0.01), and atherosclerotic etiology in proximal and middle BAO occlusions (P=0.02). While distal BAO was more likely to be recanalized using intravenous thrombolysis (IVT) compared with other sites of occlusion (P=0.05), we found no difference between different occlusion sites and the success of endovascular treatment (EVT). Lower age (odds ratio (OR) 0.89; CI 0.84 to 0.95; P<0.01) and shorter time to intervention (OR 0.71; CI 0.53 to 0.95; P=0.02), regardless of it being IVT or EVT, were predictors of an excellent clinical outcome (mRS 0-2). Distal occlusion (OR 28; CI 2.7 to 300; p<0.01) was a strong predictor of a favorable clinical outcome (mRS 0-3). CONCLUSION: Prompt reperfusion, regardless of it being IVT or EVT, increases the chance of excellent clinical outcomes in patients with acute BAO. Distal BAO is more often associated with a favorable clinical outcome compared with the proximal and middle segments.

Mind the Gap: Acetazolamide Prolonged Periods without Paralysis in a Girl with Andersen-Tawil Syndrome.

We present a case report of a 13-year-old girl with Andersen-Tawil Syndrome (ATS), a rare genetic disorder which is characterized by dysmorphic features, ventricular arrhythmias, and frequent episodes of muscle paralysis that interfere with daily activities and social engagement. After the introduction of off-label treatment with acetazolamide periods without paralysis lengthened, our patient became more independent of the help of her parents and required a wheelchair less frequently, thus improving her social life. Based on our experience, we recommend a trial of acetazolamide in patients with ATS.