Phenotypic characterization of seven individuals with Marbach-Schaaf neurodevelopmental syndrome.

We present the phenotypes of seven previously unreported patients with Marbach-Schaaf neurodevelopmental syndrome, all carrying the same recurrent heterozygous missense variant c.1003C>T (p.Arg335Trp) in PRKAR1B. Clinical features of this cohort include global developmental delay and reduced sensitivity to pain, as well as behavioral anomalies. Only one of the seven patients reported here was formally diagnosed with autism spectrum disorder (ASD), while ASD-like features were described in others, overall indicating a lower prevalence of ASD in Marbach-Schaaf neurodevelopmental syndrome than previously assumed. The clinical spectrum of the current cohort is similar to that reported in the initial publication, delineating a complex developmental disorder with behavioral and neurologic features. PRKAR1B encodes the regulatory subunit R1ß of the protein kinase A complex (PKA), and is expressed in the adult and embryonal central nervous system in humans. PKA is crucial to a plethora of cellular signaling pathways, and its composition of different regulatory and catalytic subunits is cell-type specific. We discuss potential molecular disease mechanisms underlying the patients' phenotypes with respect to the different known functions of PKA in neurons, and the phenotypes of existing R1ß-deficient animal models.

Epilepsy awareness among school-aged students in Poland.

OBJECTIVE: Epilepsy can be a well-controlled condition with only a slight impact on patients' life. Lack of knowledge within society contributes to children with epilepsy experiencing discrimination and hostility. The aim of this study was to evaluate the awareness of epilepsy and general views on people struggling with this disease among school-aged children. METHODS: The study was conducted on a random sample of Polish school students, in total 472 participants. Participants' knowledge was assessed by a self-completed survey. RESULTS: Students are unaware of the wide range of symptoms occurring during seizures. More than half claimed that people experiencing epilepsy should not perform sports activities. Alarmingly, 30% of participants believe that those patients should not leave the house and they should be excluded from many jobs. Almost all participants would help a person experiencing seizures and remember proper head protection; shockingly, 20% of children would try to put something in the person's mouth. Older students seem to be better educated on epilepsy, but the percentage of incorrect personal beliefs and myths is similar for each age group. SIGNIFICANCE: School-aged students have insufficient knowledge of epilepsy. More emphasis should be put on first aid during seizures and on the spectrum of epilepsy symptoms. Educating society is important for life quality of people experiencing epilepsy.

Protocol of safe vaccination against COVID-19 in patients with high risk of allergic reactions.

Background: Sars-CoV-2 infections are hazardous, especially to the elderly and patients with comorbidities. With no efficient treatment available, newly developed vaccines are the only way to change the course of the pandemic. However, reports of allergic reactions resulted in some patients and practicing physicians being concerned about the safety of vaccine administration, particularly in people with severe anaphylactic reactions to multiple or unknown factors in their medical history.This study aimed to develop an allergic work-up protocol based on skin prick tests (SPT), intradermal testing (IDT) and intramuscular provocations, and desensitisation which may contribute to diagnosis and management of anti-COVID-19 vaccine allergy. Methods: Two hundred and eighty-five patients were enrolled. Two hundred and five of them entered the study based on severe anaphylactic reaction to unknown or multiple factors in their medical history which disqualified them for standard treatment. Another 80 patients were enrolled after developing an allergic reaction to the first dose of one such vaccine. In all subjects, SPT and IDT were performed. Serum tryptase was assessed in 79 patients randomly chosen from the study group. Results: Two hundred and seventy-seven patients with negative tests were given a vaccine without complications. Seven patients had positive skin tests. In two cases, tests confirmed Comirnaty allergy, while the other five confirmed solely skin sensitisation with no exposure prior to the study. Six patients with positive tests received titrated challenge using desensitisation protocol with a reasonable tolerance. One patient did not consent to desensitisation and one patient resigned despite negative tests. Overall, 283 (99%) patients were vaccinated using this newly developed protocol. Patients with adverse reactions to the first dose of the vaccine before the study had a significantly lower basal serum tryptase concentration (p = 0.001). Conclusion: Skin tests with anti-COVID-19 vaccines are a useful tool in the vaccination protocol. This protocol enables safe immunisation of high-allergy-risk patients even in cases of positive skin tests.