Posterior fossa tumors are the most common solid pediatric neoplasms, and more than 60
Abstract Background Hopkins syndrome (HS) is a rare neuromuscular disorder characterized by poliomyelitis-like flaccid paralysis occurring in children after an acute asthma attack. This report describes the multimodal neurophysiological and ultrasonographic evaluation of a child presenting with post-asthmatic lower limb weakness and discusses the differential diagnosis of flaccid paralysis in childhood. Case presentation A 2-year-old boy presented with left leg weakness two weeks after an asthma exacerbation; one month after symptom onset, he was unable to walk without assistance. The child’s past medical history was significant only for asthma, and his vaccination schedule, including for poliomyelitis, was up to date. Neurological examination revealed left lower limb weakness with areflexia (absent reflexes) and moderate atrophy. Electroneuromyography and muscle ultrasound indicated a chronic, asymmetric anterior horn cell disease without evidence of acute denervation. Conclusion HS is a rare neuromuscular disorder characterized by poliomyelitis-like paralysis that occurs in children following an acute asthma attack. Given its rarity, the pathophysiology and optimal management strategies for HS remain poorly understood. A multimodal assessment combining ultrasound and neurophysiological studies is valuable for improving the characterization of this phenotype.
Interferonopathies are rare autoinflammatory disorders driven by a constitutive upregulation of the type I interferon (IFN-I) pathway, leading to chronic activation of this cytokine. Despite advances, direct IFN-I measurement is challenging, making diagnosis reliant on clinical suspicion and genetic testing, which often yields inconclusive results due to a lack of established clinical criteria and the limited number of genes described as related to interferonopathies. Indirect methods, such as the “IFN signature” (expression of interferon-stimulated genes—ISGs), are used, but many patients still lack a confirmed genetic diagnosis. To this end, we aim to evaluate the clinical utility of the interferon signature as a diagnostic screening tool and to integrate it with genetic analysis in a cohort of Brazilian patients with suspected interferonopathy. We conducted a cross-sectional study within the Centro nacional de Erros Inatos da Imunidade e Imunodesregulação (CNE3i) (Certificate of Presentation for Ethical Consideration [CAAE]: 73174223.1.1001.0068). Patients with clinical suspicion of interferonopathy underwent peripheral blood collection for peripheral blood mononuclear cell (PBMC) isolation and RNA/DNA extraction. The IFN-I signature was assessed via quantitative PCR (qPCR) of a 6-gene panel (IFI27, ISG15, IFI44L, RSAD2, IFIT1, and SIGLEC1), and the IS (interferon score) was determined. All patients underwent exome sequencing (NovaSeqX), and Illumina EMEDGENE was used for secondary analysis. To date, 73 patients have been evaluated. The IS confirmed IFN-1 pathway activation (resulted positive) in 43/73 cases (59%). Among those with IS-positive patients, 27 (62%) remain without a definitive genetic diagnosis (Figure 1). Targeted reanalysis searching for genes involved in nucleic acid metabolism from exome data in 11 cases with positive IS identified potentially relevant variants of uncertain significance (VUS) in genes associated with interferonopathy (RNASEH2A, ADAR1, SAMHD1, PNPT1, and ATM). The interferon signature proved to be a highly effective front-line screening test, accurately stratifying 59% of clinically suspected cases. Its high positivity rate among undiagnosed patients (62%) underscores its critical role in confirming the pathophysiological mechanism and prioritizing cases for advanced genomic investigation. The IS significantly aids in differentiating interferonopathies from other syndromes, reducing diagnostic delay, and providing a functional biomarker for future therapeutic monitoring. FINEP funding: 0956/24; FAPESP funding: 2023/09965-0; Instituto de Investigação em Imunologia funding CNPQ/MCTI: 408685/2024-7.Figure 1.Interferon signature in suspected interferonopathies at the CNE3i (Centro Nacional de Erros Inatos da Imunidade e Imunodesregulação) in Brazil. (1) The number of samples received and the main clinical phenotypes. (2) The samples that have already been analyzed, along with the mean interferon score and the mean level of IFN gene expression. (3) The number of individuals who have already been sequenced and the top three diagnoses identified at the CNE3i. IS, interferon score; AGS, Aicardi-Goutières syndrome; PRAAS, proteasome-related autoinflammatory diseases; COPA, coatomer subunit alpha Protein; SAVI, STING-associated vasculopathy with infant onset; SPENCD, spondyloenchondrodysplasia with immune dysregulation.
OBJECTIVE:To identify clinicopathologic predictors independently associated with cervical lymph node metastasis in pediatric papillary thyroid carcinoma. SUBJECTS AND METHODS:We performed a retrospective cohort including patients younger than 18 years who underwent total thyroidectomy for papillary thyroid carcinoma (PTC) (2013-2023) at a tertiary pediatric hospital in Brazil. Clinical and histopathologic variables were reviewed per World Health Organisation Classification 5th edition (2022) and the College of American Pathologists protocol (2023). Multivariable associations with cervical lymph node metastasis (LNM) were estimated using Firth's penalized logistic regression; discrimination was summarized by the area under the ROC curve (AUC) with 95% bootstrap confidence intervals. RESULTS:Thirty-two patients were included (median age, 14 years; 81% female). Cervical LNM occurred in 78%. Extrathyroidal extension (ETE) was associated with cervical lymph node metastasis in bivariate analysis (100% vs 59%; p = 0.007) and remained independently associated with cervical lymph node metastasis after adjustment for tumor T stage and lymphatic invasion (OR, 14.29; 95% CI, 1.28-2028.82; p = 0.028). CONCLUSION:ETE was independently associated with cervical lymph node metastasis in pediatric PTC and may justify closer postoperative surveillance.
Background and Objectives:ATP1A3-related disorders comprise an expanding group of ultra-rare neurologic conditions, classically including rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome. However, accumulating reports suggest a broader and overlapping phenotypic spectrum. In this context, we established the ATP1A3 Study Group to comprehensively characterize the phenotypic and genotypic spectrum of ATP1A3-related disorders in a Brazilian cohort. Methods:We conducted a multicenter, cross-sectional study of individuals with ATP1A3 variants. Cases were recruited across reference centers in 9 Brazilian states, with standardized extraction of demographic, genetic, neuroimaging, EEG, ECG, and clinical data. Variants were annotated using transcript NM_152296.5 (hg19). AlphaFold was used for structural visualization. Multiple correspondence analysis (MCA) was performed to explore symptom clustering. This study was approved by the Ethics Committee of Federal University of São Paulo (Approval No.: 82533124.0.0000.5505). Results:A total of 41 patients with ATP1A3 variants were included. Seven phenotypic categories were represented: AHC (17/41), RDP (10/41), CAPOS (7/41), relapsing encephalopathy with cerebellar ataxia (RECA; 4/41), fever-induced paroxysmal weakness and encephalopathy (FIPWE; 1/41), developmental and epileptic encephalopathy 99 (DEE99; 1/41), and malformation of cortical development (MCD; 1/41). Two neonatal-onset cases (DEE99 and MCD) were fatal. We identified 22 distinct ATP1A3 variants, including 4 novel variants (p.Gln920His, p.Arg827Gly, p.Glu670Ala, and c.606+5G>T). Clinical overlap was substantial: Cognitive impairment and seizures occurred across all phenotypes; hypotonia was present in 6 of 7 main phenotypes; abnormal eye movements and fever-induced symptoms occurred in all except MCD; and paroxysmal symptoms were reported in all, except DEE99. MCA demonstrated no discrete clustering by classical phenotype, reinforcing the continuous nature of the ATP1A3 spectrum. ECG abnormalities were rare in our cohort (1/20). Discussion:Our findings expand the clinical and genetic landscape of ATP1A3-related disorders and underscore major phenotypic overlap among classical syndromes. The results highlight the need for a unified diagnostic framework. This study also demonstrates the feasibility and scientific value of coordinated rare disease research in resource-limited settings.
