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IntroductionWilliams-Beuren syndrome (WBS) is a rare genetic disorder characterized by congenital heart defects, dysmorphic features, intellectual delay, and a distinctive social behavioral profile. This highly recurrent and homogeneous phenotype has been curiously reported to be associated with autism spectrum disorders (ASD). Both genetic and environmental origins have been implicated. This study aimed to describe Tunisian patients associated with WBS and ASD and explore the underlying etiologies.MethodsThirty-one clinically suspected WBS were referred for genetic exploration. A comprehensive evaluation using karyotyping, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (array-CGH) was performed.ResultsAll patients were clinically diagnosed and confirmed to have WBS through karyotyping and FISH analysis. Notably, six patients with complex or atypical clinical presentations underwent array-CGH. Two of these patients presented with ASD. Array CGH showed microdeletions ranging from 1.4 to 1.7 Mb in the 7q11.2 region. Further analysis of the extended region deletion identified a gene closely located in the deleted region, the HIP1 gene, involved in the central nervous system trafficking protein.DiscussionThe recurrent deletion in WBS, as well as the mirror duplication, may contribute to ASD development in some cases, suggesting a potential involvement of the ASD genes pathway in this region. However, recessive genetic origins should also be considered, particularly in consanguineous families. Furthermore, our findings highlight the potential role of genetic factors and regulatory elements within the deleted region in modulating gene expression, notably the HIP1 gene. This underscores the implications of gene dosage and environmental factors in the broader WBS region, notably with language and social development.ConclusionThe presence of ASD in WBS patients emphasizes the need to investigate all WBS patients for autistic traits to establish a better genotype–phenotype correlation. We underline the utility of array-CGH as a valuable genetic diagnostic tool for characterizing WBS cases, and we shed light on the complex interplay of behavioral disorders in the 7q11.2 region rearrangements.

Abstract Background Patients with Down syndrome are at a higher risk of developing autoimmune disorders such as thyroiditis, diabetes, and celiac disease compared with the general population. Although some diseases are well known to be associated with Down syndrome, others such as idiopathic pulmonary hemosiderosis and ischemic stroke due to protein C deficiency remain rare. Case presentation We report a case of a 2.5-year-old Tunisian girl with Down syndrome and hypothyroiditis admitted with dyspnea, anemia, and hemiplegia. Chest X-ray showed diffuse alveolar infiltrates. Laboratory tests showed severe anemia with hemoglobin of 4.2 g/dl without hemolysis. A diagnosis of idiopathic pulmonary hemosiderosis was confirmed by bronchoalveolar lavage showing numerous hemosiderin-laden macrophages, with a Golde score of 285 confirming the diagnosis of pulmonary hemosiderosis. Concerning hemiplegia, computed tomography showed multiple cerebral hypodensities suggestive of cerebral stroke. The etiology of these lesions was related to protein C deficiency. Conclusion Idiopathic pulmonary hemosiderosis remains a severe disease, which is rarely associated with Down syndrome. The management of this disease in Down syndrome patients is difficult, especially when associated with an ischemic stroke secondary to protein C deficiency.

Abstract Background Children affected by Coronavirus disease 2019 (COVID-19) showed various manifestations. Some of them were severe cases presenting with multi-system inflammatory syndrome (MIS-C) causing multiple organ dysfunction. Case presentation We report the case of a 12-year-old girl with recent COVID-19 infection who presented with persistent fever, abdominal pain and other symptoms that meet the definition of MIS-C. She had lymphopenia and a high level of inflammatory markers. She was admitted to pediatric intensive care unit since she rapidly developed refractory catecholamine-resistant shock with multiple organ failure. Echocardiography showed a small pericardial effusion with a normal ejection fraction (Ejection Fraction = 60%) and no valvular or coronary lesions. The child showed no signs of improvement even after receiving intravenous immunoglobulin, fresh frozen plasma, high doses of Vasopressors and corticosteroid. His outcome was fatal. Conclusion Pediatric patients affected by the new COVID-19 related syndrome may show severe life-threatening conditions similar to Kawasaki disease shock syndrome. Hypotension in these patients results from heart failure and the decreased cardiac output. We report a new severe clinical feature of SARS-CoV-2 infection in children in whom hypotension was the result of refractory vasoplegia.

Abstract Background Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. Case presentation Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. Conclusions The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission.

Neonatal and pediatric heart failure is commonly caused by congenital heart diseases, especially by large left-to-right shunting. It is rarely related to a Vein of Galen Aneurysmal Malformation (VGAM). Diagnosis and management of these cerebrovascular malformations in infancy are still difficult and remain a medical challenge. We report the case of a 2-month-old infant hospitalized for heart failure. In addition to symptoms relating to heart failure, the child presented in an agitated state with opisthotonic posture. Echocardiography showed dilated right heart cavities with pulmonary hypertension and no heart defect. Brain magnetic resonance imaging scanning confirmed the diagnosis of VGAM, showing multiple cerebral parenchyma damages. The baby was treated with diuretics and an angiotensin-converting-enzyme inhibitor leading to stabilization of her heart failure. Given the gravity of the neurological sequelae, no embolization procedure was planned for this child. She died 5 years later of acute heart failure.

Pseudotumoral cerebellitis in childhood is an uncommon presentation of cerebellitis mimicking a brain tumor. It often follows an inflammatory or infectious event, particularly due to varicella virus. Patients could have a wide clinical spectrum on presentation. Some patients may be asymptomatic or present at most with mild cerebellar signs, whereas others may suffer severe forms with brainstem involvement and severe intracranial hypertension mimicking tumor warranting surgical intervention. Imaging techniques especially multimodal magnetic resonance imaging represent an interesting tool to differentiate between posterior fossa tumors and acute cerebellitis. We describe a case of pseudotumoral cerebellitis in a 6-year-old girl consequent to mumps infection and review the literature on this rare association., Competing Interests: Conflict-of-interest statement: All the authors have no conflicts of interests to declare.