Mara Lucia Cordeiro

Background/Objectives: To map mental illness-related stigma and identity-based stigma and discrimination in relation to depression, anxiety, and mental health care processes among Brazilian youth. Methods: This scoping review followed PRISMA-ScR guidelines and the Arksey and O’Malley framework. PubMed/MEDLINE, Scopus, SciELO, LILACS, and CAPES were searched for studies examining stigma in relation to depression, anxiety, mental health outcomes, or care-related processes among Brazilian children and adolescents. Mixed adolescent and young-adult samples were included when they contained adolescents within the target age range. Results: Seven studies met the inclusion criteria. Stigma was identified across four domains: public, structural, self-, and courtesy stigma. Perceived discrimination was associated with major depression (aPR = 2.00, 95% CI 1.37–2.97) and severe depressive symptoms (aOR = 1.71, 95% CI 1.23–2.38) in studies examining racial discrimination and discrimination affecting sexual and gender minority youth. These estimates were derived from samples that included young adults. Qualitative evidence linked stigma to symptom concealment, barriers to help-seeking and diagnostic processes, and difficulties engaging with care. Evidence was limited by predominantly cross-sectional and qualitative designs, uneven geographic representation across Brazil, and a lack of culturally validated stigma measures. Conclusions: Stigma appears to be a multi-level factor associated with adverse mental health outcomes and with reported barriers across the mental health care pathway among Brazilian youth. Stigma-informed approaches may support earlier engagement with care among marginalized youth, but their effectiveness remains to be evaluated.

Background: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy, and data from low- and middle-income countries remain scarce. We characterized the clinical, genetic, and therapeutic profiles of patients with DS at a Brazilian tertiary referral center. Methods: This retrospective cross-sectional study included 27 patients with clinically and genetically confirmed DS (pathogenic/likely pathogenic SCN1A variants). Outcomes were ≥6-month and ≥12-month seizure freedom and seizure control in the previous month, described by treatment exposure without inferential testing. Results: The median age at seizure onset was 4 months and at diagnosis 42 months; the median individual onset-to-diagnosis interval was 29 months (range, 4–283; n = 14). All patients received polytherapy; 51.9% used cannabidiol, 40.7% vagus nerve stimulation, and 7.4% fenfluramine. Only 2/20 patients (10.0%) achieved ≥6-month and 1/20 (5.0%) ≥ 12-month seizure freedom. All six patients seizure-free in the previous month were receiving valproate, a descriptive finding likely reflecting confounding by indication. Recorded comorbidities, mainly autism spectrum disorder (29.6%), were likely underestimated in the absence of systematic neurodevelopmental assessment. Conclusions: This Brazilian DS cohort showed marked diagnostic delay, high seizure burden, and limited access to DS-specific therapies. These findings support earlier genetic testing and broader access to recommended treatments and generate hypotheses for larger prospective studies.

Background: Fragile X syndrome (FXS) requires molecular confirmation, yet diagnostic workflows vary in their capacity to characterize expansions and connect diagnosis with subsequent care. This review evaluated alignment between current recommendations and published diagnostic practice. Methods: We combined a structured review of recommendations for FMR1 molecular diagnosis, complementary testing, genetic counseling, and family testing with a scoping review of peer-reviewed primary studies reporting FMR1 diagnostic or screening workflows relevant to pediatric FXS. PubMed/MEDLINE, Embase, and Scopus were searched without date restrictions. Thirty-four studies were included, with design-specific risk-of-bias assessment and exploratory exact analyses of factors associated with post-initial FMR1 testing. Results: Molecular or genomic testing was reported in all 34 studies, but workflows ranged from conventional PCR and Southern blot to TP-PCR, methylation-sensitive assays, and sequencing-based approaches. Post-initial FMR1 testing was reported in 22/34 studies (64.7%), with positive-result follow-up documented in 19/34 (55.9%) and follow-up of inconclusive or initially negative results in 14/34 (41.2%). FMR1 sequencing was uncommon (3/34, 8.8%). Genetic counseling was addressed in 32/34 studies (94.1%), but documented as delivered in only 9/34 (26.5%); family evaluation and multidisciplinary management were also inconsistently reported. Conclusions: Published evidence broadly supports molecular FMR1 testing but shows variability in molecular characterization and downstream care. Standardization should prioritize analytically appropriate workflows, additional testing when required by the initial result or assay limitations, and stronger integration of molecular diagnosis with genetic counseling, family evaluation, and multidisciplinary management.

Background/Objectives: Chromosomal microarray analysis (CMA) is widely used in the genetic evaluation of autism spectrum disorder (ASD), yet its diagnostic contribution in clinically nonsyndromic ASD, particularly in Brazilian populations, remains insufficiently characterized. This study aimed to determine the diagnostic yield of CMA and characterize clinically relevant copy number variants (CNVs) in a cohort of individuals with clinically nonsyndromic ASD from southern Brazil. Methods: In this observational cohort study, 215 individuals with clinically diagnosed ASD underwent high-resolution CMA using the Agilent CGH + SNP Array 180K platform. Individuals with dysmorphic features, known or suspected genetic syndromes, major congenital malformations, epilepsy, or macrocephaly/microcephaly were excluded. CNVs were classified according to American College of Medical Genetics and Genomics guidelines, and the diagnostic yield was compared with that of national and international reference cohorts using Fisher’s exact test. Results: Pathogenic or likely pathogenic CNVs were identified in six individuals, corresponding to a diagnostic yield of 2.8% (95% CI, 1.3–6.1%). These included deletions at 2q11.1–q11.2, 2p16.3 (NRXN1), 15q11.2 (BP1–BP2), and 3q29, and duplications at 16p11.2 and 6p22.3–p22.2. Although the diagnostic yield was lower than that reported in phenotypically heterogeneous ASD cohorts, it did not differ significantly from yields observed in comparably selected nonsyndromic subgroups. Conclusions: CMA identified clinically relevant recurrent CNVs at neurodevelopmental loci even in a clinically nonsyndromic ASD cohort. The comparatively low diagnostic yield highlights the substantial influence of clinical and phenotypic selection on the diagnostic contribution of CMA.

Background: Visual impairment is associated with mental health difficulties in children, yet emotional and behavioral profiles across different etiologies and levels of visual impairment remain poorly characterized. We investigated whether these outcomes were associated with syndromic etiology or visual impairment severity. Methods: In this cross-sectional study, parents of 69 children and adolescents aged 6–17 years with visual impairment completed the Child Behavior Checklist (CBCL/6–18). Participants were grouped by etiology (syndromic, n = 14; non-syndromic, n = 55) and by visual impairment severity (mild-to-moderate, n = 33; severe-to-profound, n = 36). Group differences were assessed using Mann–Whitney U tests with false discovery rate (FDR) correction, complemented by categorical analyses using scale-specific CBCL clinical thresholds. Results: No significant differences in emotional or behavioral symptoms were observed between the syndromic and non-syndromic groups, although the small syndromic subgroup limited statistical power. In contrast, children with mild-to-moderate visual impairment had significantly higher scores on the Anxious/Depressed and Somatic Complaints scales than those with severe-to-profound impairment, with both differences remaining significant after FDR correction. Categorical analyses also showed a higher prevalence of clinically significant Anxious/Depressed and Internalizing Problems in the mild-to-moderate group. Conclusions: Children with mild-to-moderate visual impairment exhibited higher Anxious/Depressed and Somatic Complaints scores than those with severe-to-profound impairment. These findings suggest that children with residual vision may represent an underrecognized subgroup at risk for emotional difficulties and support routine psychological screening across the spectrum of pediatric visual impairment.

Background/Objectives: Timely identification of autism spectrum disorder (ASD) is essential for access to early intervention; however, diagnostic delay remains a persistent challenge. Methods: This scoping review synthesized evidence from eight studies (>24,000 participants), most conducted in the Southeast region, on diagnostic pathways, screening practices, and barriers to ASD identification in Brazil, following PRISMA-ScR guidelines. Results: Across studies, mean age at diagnosis frequently exceeded 48–60 months, while the interval between first caregiver concern and diagnosis ranged from 24 to 36 months, with tertiary-care samples reporting diagnostic ages approaching 79 months. Diagnosis was predominantly specialist-driven, with limited involvement of primary care providers (PCPs). Later identification was associated with reliance on the public health system in a multinational analysis that included Brazil, while geographic concentration of specialized services and socioeconomic inequalities were identified as reported barriers across the included studies. Race/ethnicity was rarely reported. Delays emerged from interacting multilevel barriers, including limited caregiver awareness, dismissal of parental concerns, inconsistent developmental surveillance, fragmented referral pathways, and shortages of specialists. Structural inequities, particularly geographic disparities and urban concentration of services, compounded these challenges. Conclusions: The evidence suggests delayed ASD diagnosis in Brazil reflects systemic gaps in care organization rather than isolated clinical factors. Strengthening PCP-based developmental surveillance and improving referral coordination are key strategies to reduce preventable delays and promote earlier access to intervention.

Objective: To characterize neurodevelopmental disorders in children and adolescents with Tuberous Sclerosis Complex (TSC) and explore associations with epilepsy onset and cortical tuber burden. Methods: This exploratory cross-sectional study included 18 children and adolescents with TSC followed at a tertiary pediatric neurology center in Brazil. Standardized neuropsychological, behavioral, and neuroimaging assessments were performed. Participants were stratified according to epilepsy onset and cortical tuber burden. Results: Epilepsy was present in 94.4% of participants, and pharmacoresistance in 52.9%. Neurodevelopmental disorders were highly prevalent, particularly autism spectrum disorder and attention-deficit/hyperactivity disorder, frequently occurring as comorbidities. Children with earlier epilepsy onset demonstrated exploratory trends toward poorer cognitive outcomes, whereas greater cortical tuber burden showed exploratory trends toward greater behavioral and emotional dysregulation, although these differences did not reach statistical significance. Conclusions: Neurodevelopmental disorders are highly prevalent in pediatric TSC. Exploratory findings suggest that epilepsy characteristics and lesion burden may be related to cognitive and behavioral outcomes. These exploratory findings support systematic multidisciplinary neurodevelopmental monitoring in children with TSC.

Objective: Visual impairment (VI) affects millions of children worldwide and may influence neurodevelopmental processes beyond sensory functioning. Although cross-modal plasticity has been proposed as a compensatory mechanism, the extent to which VI severity affects verbal learning and executive functioning during development remains unclear. This study examined verbal and executive function profiles in children and adolescents with different degrees of VI. Methods: Eighty-six children and adolescents with VI, aged 6–16 years, were assessed using standardized measures. Verbal comprehension and working memory were evaluated with the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV). Executive functioning was assessed through caregiver reports using the Behavior Rating Inventory of Executive Function (BRIEF), and auditory-verbal memory was explored using the Rey Auditory Verbal Learning Test (RAVLT). Participants were categorized according to VI severity: mild-to-moderate versus severe-to-profound. Group differences were analyzed using Mann–Whitney U tests, with statistical significance set at p < 0.05. Results: Participants with severe-to-profound VI showed significantly lower Verbal Comprehension Index scores in both childhood and adolescence compared with those with mild-to-moderate VI. In adolescence, greater VI severity was also associated with significantly poorer adaptive functioning across communication, daily living skills, socialization, and the overall Adaptive Behavior Composite. Group differences in caregiver-reported executive functioning and Working Memory Index scores did not reach statistical significance. A group difference was observed in a specific auditory-verbal learning measure during adolescence, with higher scores in the severe-to-profound VI group. However, this finding should be interpreted cautiously as task-specific. Conclusion: VI severity is associated with differences in cognitive and adaptive functioning in pediatric populations, with a particularly consistent association with verbal comprehension and age-dependent effects on adaptive behavior. These findings highlight the importance of considering severity levels in neurodevelopmental assessment and in the design of targeted educational and rehabilitative strategies.

This case series provides a detailed description of the coexistence of spinal muscular atrophy (SMA) type 1 and autism spectrum disorder (ASD) in children treated with disease‐modifying therapies. Among 13 patients (2–7 years; mean age 4 years [SD 2 years], eight males), five met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria for ASD—a proportion substantially higher than expected and exceeding recent reports in SMA cohorts. These findings indicate that ASD may be underrecognized in this population and that traditional screening tools, such as the autism trait assessment, may fail to detect symptoms because of the severe motor and communicative limitations characteristic of SMA. Although all children demonstrated meaningful motor gains after treatment, those with SMA and ASD showed marked cognitive and adaptive impairments, particularly in communication, socialization, and daily living skills. The dissociation between motor improvement and neurodevelopmental outcomes underscores the need for tailored assessments and continuous behavioral surveillance. This report provides clinically relevant insights and highlights the importance of adapted diagnostic approaches for neurodevelopmental evaluation in SMA.

Background/Objectives: Moyamoya angiopathy is a progressive occlusive cerebrovascular disorder and a relevant cause of pediatric stroke. While most published data originate from Asian and North American populations, reports from South America remain scarce. This study aimed to characterize the clinical, angiographic, and functional outcomes of pediatric patients with Moyamoya disease (MMD) or Moyamoya syndrome (MMS) who underwent indirect revascularization in a Brazilian cohort, and to contextualize these findings within the international literature. Methods: We retrospectively reviewed all patients under 18 years of age who underwent indirect bypass (EDAS/EDAMS) for MMD or MMS at a tertiary pediatric center in Curitiba, Brazil, between 2009 and 2023. Demographic, clinical, and angiographic data were analyzed, including postoperative Matsushima grading, and functional outcomes assessed by the modified Rankin Scale (mRS) and Glasgow Outcome Scale (GOS). All eligible patients received perioperative aspirin (3–5 mg/kg/day). Results: Fourteen patients (64% female; mean age 9.9 years) were included: 43% with MMD and 57% with MMS. Hemiparesis (86%), seizures (57%), and cognitive impairment (57%) were the most common symptoms. Most were classified as Suzuki stages II–III. All underwent indirect revascularization; 79% received bilateral procedures. Angiographic follow-up (14 hemispheres) showed good collateral formation (Matsushima grade A: 43%; B: 57%). Complications occurred in three patients (21%), and two (14%)—both MMD—developed new postoperative ischemic strokes despite receiving aspirin therapy. At 3.5 years of mean follow-up, the mean mRS was 1.9 ± 0.8 and the GOS was 4.0 ± 0.3. Conclusions: Indirect revascularization in this Brazilian pediatric cohort was feasible and safe, yielding outcomes comparable to international series. Collateral development correlated with functional improvement. These exploratory findings emphasize the importance of early diagnosis, standardized perioperative care, and long-term follow-up, and highlight the need for multicenter collaboration in Latin America.