Predictors of genetic diagnosis in individuals with developmental and epileptic encephalopathies.

OBJECTIVE: To evaluate the clinical predictors of positive genetic investigation in developmental and epileptic encephalopathies, beyond the influence of Dravet Syndrome. METHODS: The study included 98 patients diagnosed with developmental and epileptic encephalopathies. The patients underwent Sanger sequencing of SCN1A, Chromosomal Microarray Analysis, and Whole Exome Sequencing. The association of clinical variables with a positive genetic test was investigated using univariate and multivariate analysis. RESULTS: Genetic diagnosis was identified in 47 (48 %) patients with developmental and epileptic encephalopathies. Beyond Dravet Syndrome influence, first seizure in the context of fever (p < 0.01), seizures precipitated by temperature (p = 0.04), cognitive regression (p = 0.04), hypotonia (p < 0.01), and focal seizures (p = 0.03) increased the chances of a positive genetic investigation. In contrast, atonic seizures (p = 0.01) and generalized discharges on electroencephalogram (p = 0.02) decreased the chances. Dravet Syndrome was positively associated with a genetic developmental and epileptic encephalopathies etiology (p < 0.01), whereas epilepsy with myoclonic-atonic seizures (p = 0.01), developmental and epileptic encephalopathies with spike-wave activation in sleep (p = 0.04), and Lennox-Gastaut syndrome (p = 0.03) were negatively associated. In multivariate analysis, the first seizure in the context of fever (p < 0.01) and hypotonia (p = 0.02) were positively, and atonic seizures (p = 0.01) were negatively and independently associated with a genetic etiology. CONCLUSION: The predictive variables of genetic investigation in developmental and epileptic encephalopathies are first seizure in the context of fever and hypotonia, whereas atonic seizures decrease the chances of finding a genetic cause for developmental and epileptic encephalopathies. Regarding epileptic syndromes, Dravet Syndrome is highly associated with a positive genetic test, whereas epilepsy with myoclonic-atonic seizures, developmental and epileptic encephalopathies with spike-wave activation in sleep, and Lennox-Gastaut syndrome are rarely associated with a positive genetic investigation.

International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions.

The 2017 International League Against Epilepsy classification has defined a three-tier system with epilepsy syndrome identification at the third level. Although a syndrome cannot be determined in all children with epilepsy, identification of a specific syndrome provides guidance on management and prognosis. In this paper, we describe the childhood onset epilepsy syndromes, most of which have both mandatory seizure type(s) and interictal electroencephalographic (EEG) features. Based on the 2017 Classification of Seizures and Epilepsies, some syndrome names have been updated using terms directly describing the seizure semiology. Epilepsy syndromes beginning in childhood have been divided into three categories: (1) self-limited focal epilepsies, comprising four syndromes: self-limited epilepsy with centrotemporal spikes, self-limited epilepsy with autonomic seizures, childhood occipital visual epilepsy, and photosensitive occipital lobe epilepsy; (2) generalized epilepsies, comprising three syndromes: childhood absence epilepsy, epilepsy with myoclonic absence, and epilepsy with eyelid myoclonia; and (3) developmental and/or epileptic encephalopathies, comprising five syndromes: epilepsy with myoclonic-atonic seizures, Lennox-Gastaut syndrome, developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep, hemiconvulsion-hemiplegia-epilepsy syndrome, and febrile infection-related epilepsy syndrome. We define each, highlighting the mandatory seizure(s), EEG features, phenotypic variations, and findings from key investigations.

Social cognition in childhood epilepsy with centrotemporal spikes.

PURPOSE: Social cognition is involved in the perception, processing, and interpretation of social information. For this reason, social cognition is a crucial domain for successful communication and interpersonal relationships. With this in mind, we aimed to assess social cognition in children with Self-Limited Childhood Epilepsy with Centrotemporal Spikes (CECTS) and its association with traditional executive function tests and clinical variables of epilepsy. METHODS: We evaluated 23 patients with CECTS (65% male, mean age of 10.64 years) and 20 healthy children (75% male, mean age of 10.15 years). We used the Faux-Pas Child Task (FP) to analyze social cognition and a comprehensive battery of neuropsychological tests to evaluate domains of classic executive functions. RESULTS: Patients with CECTS had impairments in FP compared to healthy children [p < 0.001]. Impairments in some areas of traditional executive functions were related to worse social cognition in patients with CECTS. Epilepsy-related factors did not impair the performance on FP, except for the number of antiseizure medication [p = 0.016]. CONCLUSIONS: Social cognition is impaired in children and adolescents with CECTS. The presence of ongoing seizures and frequent epileptiform activity were not correlated with social cognition. Therefore, epilepsy per se was more relevant for social cognition than its severity.

Multimodal Analysis of SCN1A Missense Variants Improves Interpretation of Clinically Relevant Variants in Dravet Syndrome.

Objective: We aimed to improve the classification of SCN1A missense variants in patients with Dravet syndrome (DS) by combining and modifying the current variants classification criteria to minimize inconclusive test results. Methods: We established a score classification workflow based on evidence of pathogenicity to adapt the classification of DS-related SCN1A missense variants. In addition, we compiled the variants reported in the literature and our cohort and assessed the proposed pathogenic classification criteria. We combined information regarding previously established pathogenic amino acid changes, mode of inheritance, population-specific allele frequencies, localization within protein domains, and deleterious effect prediction analysis. Results: Our meta-analysis showed that 46% (506/1,101) of DS-associated SCN1A variants are missense. We applied the score classification workflow and 56.5% (286/506) of the variants had their classification changed from VUS: 17.8% (90/506) into "pathogenic" and 38.7% (196/506) as "likely pathogenic." Conclusion: Our results indicate that using multimodal analysis seems to be the best approach to interpret the pathogenic impact of SCN1A missense changes for the molecular diagnosis of patients with DS. By applying the proposed workflow, most DS related SCN1A variants had their classification improved.

Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission.

Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.

The relevance of attention deficit hyperactivity disorder in self-limited childhood epilepsy with centrotemporal spikes.

In this study, we aimed to evaluate the attentional and executive functions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS) with and without attention-deficit hyperactivity disorder (ADHD) compared with controls and compared with patients with ADHD without epilepsy. We evaluated 12 patients with BCECTS and ADHD (66.7% boys; mean age of 9.67years); 11 children with non-ADHD BCECTS (63.6% boys; mean age of 11.91years); 20 healthy children (75% boys; mean age of 10.15years); and 20 subjects with ADHD without epilepsy (60% boys; mean age of 10.9years). We used a comprehensive battery of neuropsychological tests to evaluate attentional and executive functions in their broad domains. Patients with BCECTS and ADHD had worse performance in Conners' Continuous Performance Test II (reaction time standard error [p=0.008], variability [p=0.033], perseverations [p=0.044] and in reaction time interstimuli interval [p=0.016]). Patients with ADHD showed worse performance in Trail Making Test B errors [p=0.012]. In conclusion, patients with BCECTS and ADHD had worse executive and attentional performance compared with controls than non-ADHD patients with BCECTS. Regardless of the presence of epilepsy, ADHD also negatively impacted executive and attentional functions but in different executive subdomains compared with patients with epilepsy.

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia.

OBJECTIVE: Focal cortical dysplasias (FCDs) are an important cause of drug-resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II. METHODS: We used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study. RESULTS: hsa-let-7f (p = 0.039), hsa-miR-31 (p = 0.0078), and hsa-miR34a (p = 0.021) were downregulated in FCD type II, whereas a transcription factor involved in neuronal and glial fate specification, NEUROG2 (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2-target, is upregulated (p < 0.001). In vitro experiments showed that hsa-miR-34a downregulates NEUROG2 by binding to its 5'-untranslated region. Moreover, we observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic neurons and found that 28.5% of our patients presented brain somatic mutations in genes of the mTOR pathway. INTERPRETATION: Our findings suggest a new molecular mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of FCD type II. In this way, we found that the downregulation of hsa-miR-34a leads to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene. These findings indicate that a faulty coupling in neuronal differentiation and migration mechanisms may explain the presence of aberrant cells and complete dyslamination in FCD type II. Ann Neurol 2018;83:623-635.

Paranasal Sinus Disease in Children With Headache.

BACKGROUND: Sinus headache is one of the most frequent misdiagnosis given to children with headache. The objective of this study is to evaluate the frequency of sinus disease in children with headache that do not fulfill the criteria for headache attributed to disorder of the nose or paranasal sinuses. METHODS: This is a prospective study conducted at the authors' pediatric neurology clinic. Data from children with headache was evaluated and compared with a disease control group composed of children without history of headache. All patients underwent neuroimaging assessment. Patients with diagnosis of acute infectious sinus disease were excluded from the analysis. The type of headache was classified according to the International Headache Society. Statistical analysis was performed using the Fisher exact test, with a level of significance of .05. RESULTS: A total of 62 patients with headache were evaluated; 24 boys, 38 girls, ages ranging from 3 to 18 years (mean = 9.7 years). Of the patients, 29 had migraine without aura, 4 had frequent episodic tension type headache, 3 had both migraine without aura and frequent episodic tension type headache, 3 had migraine with brainstem aura, 2 had episodic tension type headache, 1 had migraine with aura. In 20 patients the type of headache could not be established. The disease control group had 41 patients; 25 boys, 16 girls, ages ranging from 3 to 17 years (mean = 7.3 years). Sinus abnormalities detected by neuroimaging were present in 12 patients in the headache group and in 11 patients in the disease control group ( P = .469). CONCLUSION: The authors conclude that sinus abnormalities are a common finding in neuroimaging tests of children with or without headache. Sinus disease disclosed by neuroimaging evaluation should not preclude the diagnosis of migraine or other types of primary headache.

The executive profile of children with Benign Epilepsy of Childhood with Centrotemporal Spikes and Temporal Lobe Epilepsy.

RATIONALE: Benign Epilepsy of Childhood with Centrotemporal Spikes (BECTS) and temporal lobe epilepsy (TLE) represent two distinct models of focal epilepsy of childhood. In both, there is evidence of executive dysfunction. The purpose of the present study was to identify particular deficits in the executive function that would distinguish children with BECTS from children with TLE. METHODS: We prospectively evaluated 19 consecutive children and adolescents with TLE with hippocampal sclerosis (HS) (57.9% male; mean 11.74years [SD 2.05]; mean IQ 95.21 [SD 15.09]), 19 with BECTS (36.8% male; mean 10.95years [SD 2.33]; mean IQ 107.40 [SD 16.01]), and 21 age and gender-matched controls (33.3% male; mean 11.86years [SD 2.25]; mean IQ 108.67 [15.05]). All participants underwent a neuropsychological assessment with a comprehensive battery for executive and attentional functions. We used ANOVA and chi-square to evaluate differences on demographic aspects among groups (BECTS, TLE-HS, and control groups). Group comparisons on continuous variables were complemented by MANOVA and Bonferroni posthoc comparisons. RESULTS: Patients with BECTS had worse performance than controls in: Matching Familiar Figures Test, time (p=0.001); Matching Familiar Figures Test, time×errors index (p<0.001); Verbal Fluency for foods (p=0.038); Trail Making Test, part B time (p=0.030); Trail Making Test, part B number of errors (p=0.030); and WCST, number of categories achieved (p=0.043). Patients with BECTS had worse performance than patients with TLE-HS on Matching Familiar Figures Test, time (p=0.004), and Matching Familiar Figures Test, time×errors index (p<0.001). Patients with TLE-HS had worse performance than controls on the following tests: Verbal Fluency for foods (p=0.004); Wisconsin Card Sorting Test, the number of categories achieved (p<0.001); and Wisconsin Card Sorting Test, the number of perseverative errors (p=0.028). Patients with TLE-HS had worse performance than patients with BECTS on Digit Backward (p=0.002); and the Wisconsin Card Sorting Test, the number of perseverative errors (p<0.001). CONCLUSIONS: Patients with TLE and BECTS present distinct cognitive profiles. Patients with TLE-HS had worse performance in mental flexibility, concept formation, and working memory compared to BECTS. Patients with BECTS had worse inhibitory control compared to children with TLE-HS. Both TLE-HS and BECTS had a higher number of errors on an inhibitory control test. However, patients with BECTS had a slower mental processing even when compared to patients with TLE-HS. Rehabilitation programs for children with epilepsy must include children with benign epilepsies and must take into account the epileptic syndrome and its particular neurocognitive phenotype.

The impact of intelligence on memory and executive functions of children with temporal lobe epilepsy: Methodological concerns with clinical relevance.

PURPOSE: Patients with TLE are prone to have lower IQ scores than healthy controls. Nevertheless, the impact of IQ differences is not usually considered in studies that compared the cognitive functioning of children with and without epilepsy. This study aimed to determine the effect of using IQ as a covariate on memory and attentional/executive functions of children with TLE. METHODS: Thirty-eight children and adolescents with TLE and 28 healthy controls paired as to age, gender, and sociodemographic factors were evaluated with a comprehensive neuropsychological battery for memory and executive functions. The authors conducted three analyses to verify the impact of IQ scores on the other cognitive domains. First, we compared performance on cognitive tests without controlling for IQ differences between groups. Second, we performed the same analyses, but we included IQ as a confounding factor. Finally, we evaluated the predictive value of IQ on cognitive functioning. RESULTS: Although patients had IQ score in the normal range, they showed lower IQ scores than controls (p = 0.001). When we did not consider IQ in the analyses, patients had worse performance in verbal and visual memory (short and long-term), semantic memory, sustained, divided and selective attention, mental flexibility and mental tracking for semantic information. By using IQ as a covariate, patients showed worse performance only in verbal memory (long-term), semantic memory, sustained and divided attention and in mental flexibility. IQ was a predictor factor of verbal and visual memory (immediate and delayed), working memory, mental flexibility and mental tracking for semantic information. CONCLUSION: Intelligence level had a significant impact on memory and executive functioning of children and adolescents with TLE without intellectual disability. This finding opens the discussion of whether IQ scores should be considered when interpreting the results of differences in cognitive performance of patients with epilepsy compared to healthy volunteers.

Comparison of auditory event-related potentials between children with benign childhood epilepsy with centrotemporal spikes and children with temporal lobe epilepsy.

The abnormal brain discharges observed in benign childhood epilepsy with centrotemporal spikes (BECTS) and temporal lobe epilepsy (TLE) are located close to areas responsible for auditory and language processing. This study aimed to analyze the results of auditory event-related potentials (P300) in children with BECTS and TLE in order to assess whether the epileptic activity in centrotemporal and temporal regions may compromise the integrity and physiology of auditory system structures. This was a prospective, comparative, and cross-sectional study. Group I (GI) consisted of 13 children diagnosed with BECTS, group II (GII), 7 children diagnosed with TLE, and control group (GIII), 16 healthy children, with no hearing or academic complaints. After neurological and basic audiological assessments, P300 was applied. The P300 latency and amplitude were compared between groups. Regarding latency, GI showed 324.1 (+31.5) ms, GII 336.3 (+23.5) ms, and GIII 318 (+27.7) ms. Amplitudes were 4.80 (+3.2) µV in GI, 4.7 (+2.5) µV in GII, and 5.8 (+2.4) µV in GIII. Although children with BECTS showed prolonged latencies and reduced amplitudes, these differences were not considered statistically significant. Children with TLE showed statistically significant prolonged P300 latency compared with the control group (P=0.037). We speculate that abnormal electrical discharges in centrotemporal and temporal regions led to the slowing of auditory processing in our sample.

Twin-twin transfusion syndrome: neurodevelopment of infants treated with laser surgery.

OBJECTIVE: To assess the neurodevelopmental functions of survivors of twin-twin transfusion syndrome (TTTS) treated by fetoscopic laser coagulation (FLC), during the first year of life, comparing them to a control group; and to verify the influence of specific variables on neurodevelopment. METHOD: This was a prospective, longitudinal study. The sample comprised 33 monochorionic diamniotic twins who underwent FLC for treatment of TTTS and 22 full-term infants of single-fetus pregnancies. Bayley Scales of Infant and Toddler Development Screening Test were used for evaluation. Prenatal, perinatal and postnatal information were obtained. RESULTS: There was an increased frequency of infants in the TTTS group with inadequate performance compared to the control group. The identified variables (fetal donor, low economic income and cardiorespiratory disease) negatively impacted expressive communication and fine motor skills. CONCLUSION: Although through follow-up is recommended in all TTTS survivors, particular attention is required for the high-risk group as defined in this study.

Twin-twin transfusion syndrome: neurodevelopment of infants treated with laser surgery / Síndrome de transfusão feto-fetal: neurodesenvolvimento de lactentes tratados com cirurgia a laser

ABSTRACT Objective To assess the neurodevelopmental functions of survivors of twin-twin transfusion syndrome (TTTS) treated by fetoscopic laser coagulation (FLC), during the first year of life, comparing them to a control group; and to verify the influence of specific variables on neurodevelopment. Method This was a prospective, longitudinal study. The sample comprised 33 monochorionic diamniotic twins who underwent FLC for treatment of TTTS and 22 full-term infants of single-fetus pregnancies. Bayley Scales of Infant and Toddler Development Screening Test were used for evaluation. Prenatal, perinatal and postnatal information were obtained. Results There was an increased frequency of infants in the TTTS group with inadequate performance compared to the control group. The identified variables (fetal donor, low economic income and cardiorespiratory disease) negatively impacted expressive communication and fine motor skills. Conclusion Although through follow-up is recommended in all TTTS survivors, particular attention is required for the high-risk group as defined in this study.

RESUMO Objetivo Avaliar o desenvolvimento neurológico de sobreviventes da sindrome de transfusão feto-fetal (STFF) submetidos à coagulação a laser por fetoscopia (CLF), durante o primeiro ano de vida, comparando estes ao grupo controle; e verificar a influência de variáveis específicas no desenvolvimento. Método Tratou-se de estudo prospectivo, longitudinal. A amostra foi composta por 33 gêmeos diamnióticos monocoriônicos submetidos à CLF para tratamento da STFF e 22 lactentes a termo de gestação única. Bayley Scales of Infant and Toddler Development Screening Test foram utilizadas para avaliação. Informações pré-natal, perinatal e pós-natal foram coletadas. Resultados Houve maior número de lactentes com desempenho inadequado no grupo STFF do que no controle. As variáveis identificadas (feto doador, baixa renda econômica e doença cárdio-respiratória) influenciaram negativamente a comunicação expressiva e as habilidades motoras finas. Conclusão Embora o acompanhamento seja recomendado para todos lactentes com STFF, especial atenção deve ser dada àqueles que apresentam fatores de risco.

Language and central temporal auditory processing in childhood epilepsies.

Because of the relationship between rolandic, temporoparietal, and centrotemporal areas and language and auditory processing, the aim of this study was to investigate language and central temporal auditory processing of children with epilepsy (rolandic epilepsy and temporal lobe epilepsy) and compare these with those of children without epilepsy. Thirty-five children aged between eight and 14 years old were studied. Two groups of children participated in this study: a group with childhood epilepsy (n=19), and a control group without epilepsy or linguistic changes (n=16). There was a significant difference between the two groups, with the worst performance in children with epilepsy for the gaps-in-noise test, right ear (p<0.001) and left ear (p<0.001) tests, and duration pattern test--naming (p=0.002) and humming (p=0.002). In auditory P300, there was no significant difference in latency (p=0.343) and amplitude (p=0.194) between the groups. There was a significant difference between the groups, with the worst performance in children with epilepsy, for the auditory-receptive vocabulary (PPVT) (p<0.001) and phonological working memory (nonwords repetition task) tasks (p=0.001). We conclude that the impairment of central temporal auditory processing and language skills may be comorbidities in children with rolandic epilepsy and temporal lobe epilepsy.

Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice / Desenvolvimentos recentes na genética das encefalopatias epilépticas da infância: impacto na prática clínica

Recent advances in molecular genetics led to the discovery of several genes for childhood epileptic encephalopathies (CEEs). As the knowledge about the genes associated with this group of disorders develops, it becomes evident that CEEs present a number of specific genetic characteristics, which will influence the use of molecular testing for clinical purposes. Among these, there are the presence of marked genetic heterogeneity and the high frequency of de novo mutations. Therefore, the main objectives of this review paper are to present and discuss current knowledge regarding i) new genetic findings in CEEs, ii) phenotype-genotype correlations in different forms of CEEs; and, most importantly, iii) the impact of these new findings in clinical practice. Accompanying this text we have included a comprehensive table, containing the list of genes currently known to be involved in the etiology of CEEs.

Os avanços recentes em genética molecular permitiram a descoberta de vários genes para encefalopatias epilépticas da infância (EEIs). À medida que o conhecimento sobre os genes associados a este grupo de doenças se desenvolve, torna-se evidente que as EEIs apresentam uma série de características genéticas específicas, o que influencia o uso do teste molecular para fins clínicos. Entre as EEIs, há a presença de acentuada heterogeneidade genética e alta frequência de mutações de novo. Assim, os principais objetivos deste trabalho de revisão são apresentar e discutir o conhecimento atual a respeito de i) novas descobertas em genética molecular das EEIs, ii) correlações fenótipo-genótipo nas diferentes formas de EEIs; e, mais importante, iii) o impacto desses novos achados genéticos na prática clínica. Acompanhando o texto, incluímos uma tabela contendo a lista de genes conhecidos atualmente como envolvidos na etiologia da EEIs.

Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice.

Recent advances in molecular genetics led to the discovery of several genes for childhood epileptic encephalopathies (CEEs). As the knowledge about the genes associated with this group of disorders develops, it becomes evident that CEEs present a number of specific genetic characteristics, which will influence the use of molecular testing for clinical purposes. Among these, there are the presence of marked genetic heterogeneity and the high frequency of de novo mutations. Therefore, the main objectives of this review paper are to present and discuss current knowledge regarding i) new genetic findings in CEEs, ii) phenotype-genotype correlations in different forms of CEEs; and, most importantly, iii) the impact of these new findings in clinical practice. Accompanying this text we have included a comprehensive table, containing the list of genes currently known to be involved in the etiology of CEEs.

Effects of age and cognition on a cross-cultural paediatric adaptation of the Sniffin' Sticks Identification Test.

OBJECTIVES: To study the effects of age and cognition on the performance of children aged 3 to 18 years on a culturally adapted version of the 16 item smell identification test from Sniffin' Sticks (SS16). METHODS: A series of pilots were conducted on 29 children aged 3 to 18 years old and 23 adults to produce an adapted version of the SS16 suitable for Brazilian children (SS16-Child). A final version was applied to 51 children alongside a picture identification test (PIT-SS16-Child) to access cognitive abilities involved in the smell identification task. In addition 20 adults performed the same tasks as a comparison group. RESULTS: The final adapted SS16-Child was applied to 51 children with a mean age of 9.9 years (range 3-18 years, SD=4.25 years), of which 68.3% were girls. There was an independent effect of age (p<0.05) and PIT-SS16-Child (p<0.001) on the performance on the SS16-Child, and older children reached the ceiling for scoring in the cognitive and olfactory test. Pre-school children had difficulties identifying items of the test. DISCUSSION/CONCLUSIONS: A cross-culturally adapted version of the SS16 can be used to test olfaction in children but interpretation of the results must take age and cognitive abilities into consideration.

Twin-twin transfusion syndrome: neurodevelopmental screening test.

OBJECTIVE: To assess the neurodevelopmental functions (cognition, language and motor function) of survivors of twin-twin transfusion syndrome (TTTS). METHOD: Observational cross-sectional study of a total of 67 monochorionic diamniotic twins who underwent fetoscopic laser coagulation (FLC) for treatment of TTTS. The study was conducted at the Center for Investigation in Pediatrics (CIPED), Universidade Estadual de Campinas. Ages ranged from one month and four days to two years four months. Bayley Scales of Infant and Toddler Development Screening Test-III, were used for evaluation. RESULTS: Most children reached the competent category and were classified as having appropriate performance. The preterm children scored worse than term infants for gross motor subtest (p = 0.036). CONCLUSION: The majority of children reached the expected development according to their age. Despite the good neurodevelopment, children classified at risk should be monitored for development throughout childhood.