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Defects of the GNAS gene have been mainly associated with pseudohypoparathyroidism Ia. To date, pathogenic missense, frameshift, non-sense and splicing variants have been described in all the 13 exons of the GNAS gene. Of them, a specific mutation, namely the 4 bp deletion c.565_568delGACT, is currently considered a mutation hotspot. Recent articles performed genotype–phenotype correlations in patients with GNAS-related pseudohypoparathyroidism Ia (PHP1a) but a specific focus on this hotspot is still lacking. We reported two cases, from our department, of PHP1a associated with c.565_568delGACT deletion and performed a literature review of all the previously reported cases of the 4 bp deletion hotspot. We found a higher prevalence of brachydactyly, round face, intellectual disability and subcutaneous/heterotopic ossifications in patients with the c.565_568delGACT as compared to the other variants in the GNAS gene. The present study highlights the different prevalence of some clinical features in patients with the c.565_568delGACT variant in the GNAS gene, suggesting the possibility of a personalized diagnostic follow-up and surveillance for these patients. [ABSTRACT FROM AUTHOR]

Background: The STAG1 gene encodes a component of the cohesin complex, involved in chromosome segregation and DNA repair. Variants in genes of the cohesin complex determine clinical conditions characterized by facial dysmorphisms, upper limb anomalies, intellectual disability, and other neurological deficits. However, to date, the STAG1-related clinical phenotype has been poorly investigated (around 20 cases reported). Methods and Results: We report, for the first time, two twins affected by a syndromic neurodevelopmental disorder associated with a de novo variant in the STAG1 gene. Although both the twins showed a neurodevelopmental delay, one of them showed a more severe phenotype with greater behavioral problems, speech defects and limb apraxia. CGH array showed a 15q13.3 microduplication, inherited from an unaffected mother. Conclusions: We found different degrees of behavioral, speech and cognitive impairment in two twins affected by a neurodevelopmental disorder associated with a STAG1 variant. These findings highlight the variability of the STAG1-associated phenotype or a probable role of associated variants (like the discovered 15q13.3 microduplication) in modulating the clinical features. [ABSTRACT FROM AUTHOR]

This study examined the stability of the functional connectome (FC) over time using fingerprint analysis in healthy subjects. Additionally, it investigated how a specific stressor, namely sleep deprivation, affects individuals' differentiation. To this aim, 23 healthy young adults underwent magnetoencephalography (MEG) recording at three equally spaced time points within 24 h: 9 a.m., 9 p.m., and 9 a.m. of the following day after a night of sleep deprivation. The findings indicate that the differentiation was stable from morning to evening in all frequency bands, except in the delta band. However, after a night of sleep deprivation, the stability of the FCs was reduced. Consistent with this observation, the reduced differentiation following sleep deprivation was found to be negatively correlated with the effort perceived by participants in completing the cognitive task during sleep deprivation. This correlation suggests that individuals with less stable connectomes following sleep deprivation experienced greater difficulty in performing cognitive tasks, reflecting increased effort. [ABSTRACT FROM AUTHOR]

Delayed post‐hypoxic leukoencephalopathy (DPHLE) is a rare demyelinating syndrome that follows an episode of prolonged cerebral hypoxia after a relatively lucid intervening period of variable length. Although the pathophysiology still remains obscure, it has been suggested that hypoxic‐metabolic injuries to oligodendrocytes may play a crucial role. We describe the case of a patient with chronic respiratory problems who fell into a coma during morphine therapy. After a brief period of successful recovery, neurocognitive and behavioral disorders suddenly appeared and a diagnosis of DPHLE was made also taking into account the MRI picture. The antioxidant therapy has probably facilitated the almost complete neurological recovery within 4 weeks. A peculiar finding was the presence of anti‐CV2/CRMP5 antibodies in serum, which may stand as potential factors implicated in oligodendrocytes damage. [ABSTRACT FROM AUTHOR]

Ocrelizumab is a humanized monoclonal antibody designed to bind to the CD20 molecule, resulting in a rapid depletion of B-cells; however, it has been shown that lymphocyte subpopulations other than B-cells are affected by the drug. To review the effects of ocrelizumab on circulating lymphocytes and identify candidate biomarkers to predict and monitor treatment response. A literature search for the most relevant articles from 2006 to 2022 was conducted in PubMed and Scopus. The effect of ocrelizumab on the peripheral immune system goes beyond B-cells; it also depletes T CD20 + lymphocytes. Further, ocrelizumab reshapes the T-cell response toward a low inflammatory profile and induces an increase in T CD8 + regulatory cell percentage. A higher Body Mass Index and higher B-cell count at baseline have been associated with early B-cell reappearance. Serum neurofilament light chain reduction has been associated with treatment response. Ocrelizumab treatment exerts a broad immunomodulatory effect and may be tailored based on patients' clinical and biological profiles.

Esophageal achalasia is a chronic and progressive motility disorder characterized by absence of esophageal body peristalsis associated with an impaired relaxation of lower esophageal sphincter (LES) and usually with an elevated LES pressure, leading to an altered passage of bolus through the esophago-gastric junction. A definitive cure for achalasia is currently unavailable. Palliative treatment options provide only food and liquid bolus intake and relief of symptoms. Endoscopic therapy for achalasia aims to disrupt or weaken the lower esophageal sphincter. Intra-sphincteric injection of botulinum toxin is reserved for elderly or severely ill patients. Pneumatic dilation provides superior results than botulinum toxin injection and a similar medium-term efficacy almost comparable to that attained after surgery. Per oral endoscopic myotomy is a promising option for treating achalasia, but it requires increased experience and further objective and long-term follow up. This article will review different endoscopic treatments in achalasia, and summarize the short-term and long-term outcomes.