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Zellweger spectrum disorders (ZSD) are rare autosomal recessive disorders caused by defects in peroxisome biogenesis factor (PEX; peroxin) genes leading to impaired transport of peroxisomal proteins with peroxisomal targeting signals (PTS). Four patients, including a pair of homozygotic twins, diagnosed as ZSD by genetic study with different clinical presentations and outcomes as well as various novel mutations are described here. A total of 3 novel mutations, including a nonsense, a frameshift, and a splicing mutation, in PEX1 from ZSD patients were identified and unequivocally confirmed that the p.Ile989Thr mutant PEX1 exhibited temperature-sensitive characteristics and is associated with milder ZSD. The nature of the p.Ile989Thr mutant exhibited different characteristics from that of the other previously identified temperature-sensitive p.Gly843Asp PEX1 mutant. Transcriptome profiles under nonpermissive vs. permissive conditions were explored to facilitate the understanding of p.Ile989Thr mutant PEX1. Further investigation of molecular mechanisms may help to clarify potential genetic causes that could modify the clinical presentation of ZSD.
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Síndrome de Zellweger , Humanos , Niño , Síndrome de Zellweger/genética , Síndrome de Zellweger/complicaciones , Síndrome de Zellweger/metabolismo , Temperatura , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Fibroblastos/metabolismo , Mutación/genéticaRESUMEN
BACKGROUND/PURPOSE: Having siblings is a crucial ecological factor in children's language development. Whether siblings play a role in the language development of children with developmental delays remains unknown. This study therefore aimed to assess the association between sibling presence and changes in language trajectories of children with developmental delays before reaching early school age. METHODS: This retrospective cohort-sequential longitudinal study analyzed data from an institution designated by Taiwan's Ministry of Health and Welfare for assessing and identifying young children with developmental delays between December 2008 and February 2016. We included 174 children, aged 10-58 months (mean [standard deviation (SD)], 31.74 [10.15] months), with developmental delays who underwent at least three waves of evaluation. The final evaluation occurred at 37-90 months of age. Data collection spanned over an age from 10 to 90 months. The primary outcome was language delays as determined by board-certified speech-language pathologists. RESULTS: Of the 174 participants (131 boys), 64.94 % (n = 113) had siblings. The likelihood of both receptive language delay and expressive language delay for participants with siblings increased gradually from 10 to 90 months and exceeded that of participants without siblings, respectively (adjusted odds ratios [aOR], 1.04, 1.04; 95 % confidence interval [CI], 1.01-1.07, 1.01-1.07; P = 0.014, 0.020). CONCLUSION: Having siblings does not necessarily positively associate with language development in children with developmental delays. Clinicians should consider the association of sibling presence with language development for these children in a broader familial-ecological context before they reach early school age.
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Trastornos del Desarrollo del Lenguaje , Hermanos , Niño , Preescolar , Humanos , Desarrollo del Lenguaje , Trastornos del Desarrollo del Lenguaje/epidemiología , Estudios Longitudinales , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: KCNQ2-associated epilepsy is most common in neonatal genetic epilepsy. A prompt diagnosis to initialize early treatment is important. METHODS: We studied the electroencephalographic (EEG) changes including automated EEGs and conventional EEGs monitoring of 10 nonconsanguineous cases with KCNQ2 mutations, identified among 162 (6%) childhood epilepsy. We compared 11 (25%) non-KCNQ2 seizures videoed from 44 automated EEG and EEG monitoring. RESULTS: Patients with KCNQ2 seizures had received more antiepileptic treatments than patients in non-KCNQ2 group. Seizures were detected in all patients with KCNQ2 epileptic encephalopathy (EE); the detection rate in KCNQ2 group was more than in patients with non-KCNQ2. The ictal recordings showed 3 newborns presented with initial lower amplitudes (<15 µV) and fast activity (>20 Hz), evolving into higher-amplitude theta-delta waves. Two patient's ictal seizures showed recurrent focal tonic movements of the unilateral limbs associated with slowly continuous spikes in the contralateral hemisphere. The interictal EEGs in 5 KCNQ2 EE were burst-suppression. In 5 patients with familial KCNQ2 mutations, the interictal EEGs showed focal paroxysmal activity. Compared with 11 non-KCNQ2 EEG of ictal seizures, the differences are ictal EEGs initially appeared manifesting theta-delta waves without fast activities. In KCNQ2 seizures, patients with mutations locating in the selectivity filter controlling K+ permeability had severe EEG patterns and poor neurodevelopmental outcomes. CONCLUSION: Ictal EEGs in KCNQ2 seizures are unique and different from the EEGs of seizures with other etiologies. An EEG monitoring can be a valuable tool for early diagnosing KCNQ2-associated seizures and for supporting prompt treatments.
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Electroencefalografía , Epilepsia , Canal de Potasio KCNQ2/genética , Anticonvulsivantes/uso terapéutico , Niño , Diagnóstico Precoz , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Humanos , Recién Nacido , Convulsiones/diagnóstico , Convulsiones/genéticaRESUMEN
PURPOSE: To establish an appropriate clinical protocol for early photoscreening in 12-to-24-month-old children at pediatric well-baby clinics. METHODS: This prospective study included a total of 277 children aged 12-24 months who visited a pediatric well-baby clinic. All participants underwent: 1) inquiry of medical history; 2) photoscreening with PlusoptiX A12; and 3) comprehensive ophthalmologic examinations. The optimal referral cut-off point for PlusoptiX was determined by receiver operating characteristic analyses. A high-risk subgroup was defined as having a birth weight <3000 g or a history of major systemic diseases, based on the results of multivariable risk factor analysis from children's medical history. A strategy of selective photoscreening focusing on the high-risk subgroup was evaluated. The main outcome measures included sensitivity, specificity, and positive and negative predictive values. RESULTS: The prevalence of amblyopia risk factors in our study population was 12.3%. A total of 172 children (62.1%) were assigned to the high-risk subgroup. Compared with the nonselective photoscreening of all 277 children, selective photoscreening of the high-risk children yielded a higher positive predictive value (59.6% vs. 46.7%, p = 0.001) while showing no difference in sensitivity (82.3% vs. 85.3%, p = 0.32), specificity (92.2% vs, 86.4%, p = 0.05), and negative predictive value (97.4% vs. 97.6%, p = 0.50). CONCLUSION: At pediatric well-baby clinics, selective photoscreening among 12-to-24-month-old children with a birth weight <3000 g or a history of major systemic diseases helped reducing the number of children need to be screened and conserving medical resources yet identifying children at risk for timely eye care.
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Ambliopía , Selección Visual , Ambliopía/diagnóstico , Ambliopía/epidemiología , Preescolar , Humanos , Lactante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
Children with attention-deficit hyperactivity disorder (ADHD) have difficulties in social interactions. Studying brain activity during social interactions is difficult with conventional artificial stimuli. This pioneering study examined the neural correlates of social perception in children with ADHD and matched controls using naturalistic stimuli. We presented 20 children with ADHD and 20 age-and-sex-matched controls with tailored movies featuring high- or low-level social interactions while recording electroencephalographic signals. Both groups exhibited synchronized gamma-band oscillations, but controls demonstrated greater inter-subject correlations. Additionally, the difference in inter-subject correlations between high- and low-interaction movies was significantly larger in controls compared to ADHD patients. Between 55 and 75 Hz comparing viewing high interaction movies with low interaction moves, controls had a significantly larger weighting in the right parietal lobe, while ADHD patients had a significantly smaller weighting in the left occipital lobe. These findings reveal distinct spatiotemporal neural signatures in social interaction processing among children with ADHD and controls using naturalistic stimuli. These neural markers offer potential for group differentiation and assessing intervention efficacy, advancing our understanding ADHD-related social interaction mechanisms.
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Trastorno por Déficit de Atención con Hiperactividad , Electroencefalografía , Interacción Social , Humanos , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Masculino , Niño , Femenino , Biomarcadores , Ritmo Gamma/fisiología , Estudios de Casos y Controles , Encéfalo/fisiopatología , AdolescenteRESUMEN
BACKGROUND: SCN1A channelopathy is the most well-known cause for epileptic encephalopathies and contributes to a wide phenotypic spectrum. The variable expressivity is troublesome for the interpretation of clinical significance and prognoses. To investigate the clinical manifestations, medications and outcomes of patients with SCN1A channelopathies, we conducted this observation retrospective study in Taiwan. METHODS: A cohort consisting of 16 patients (5 males and 11 females) from multiple centers with identified SCN1A variants was investigated and phenotypically relevant factors were recorded. The variants were identified using NGS and confirmed by Sanger sequencing. A panel of 90 epileptic-related genes was used to identify SCN1A variants and to evaluate some of the potential SCN1A modifier genes. RESULTS: The mean age of seizure onset was 10.4 months. Twelve of the sixteen patients (75%) had different degrees of neurocognitive sequela and psychobehavioral comorbidity in our cohort. Cognitive impairment was noted in all ten patients with Dravet syndrome (DS) and in two of the patients with non-DS phenotypes. A lower response rate to medications was also noted in patients with DS. Notably, a medication-specific tendency towards valproic acid (VPA), clobazam (CLB), and levetiracetam (LEV) was observed, revealing the effective pharmacotherapies for SCN1A-related seizures. An asymptomatic carrier with a reported pathogenic SCN1A variant was reviewed along with her monozygotic twin sister with DS. Nine novel SCN1A mutations are herein reported, eight of which being classified as pathogenic. CONCLUSION: Our study revealed unfavorable outcomes for patients with SCN1A variants. Some patients with SCN1A channelopathy showed specific responsiveness to the pharmacotherapies previously either recommended or contraindicated for these patients. Our study also expands the genotype and provides valuable prognostic insights in patients with SCN1A channelopathy.
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BACKGROUND: Children can become anxious when undergoing emergency medical treatment. Therefore, emergency departments should be child friendly. This study explored emergency nurses' perspectives on children's needs during emergency care. METHOD: This qualitative study employed purposive sampling to recruit 17 emergency nurses from 3 medical centers in northern and central Taiwan. Individual interviews were conducted between January and August 2021. Data were analyzed through qualitative content analysis. RESULTS: The participants had 2-23 years of experience in caring for children in emergency departments. We identified 208 unique meaning units in the interview data, 79 of which were related to child-friendly emergency care. These were classified into 42 codes across 6 categories and 27 subcategories. The six categories were timely comfort, emotional care, frontline safety, emergency response, human resources support, and treatment efficiency. CONCLUSION: Emergency nurses have professional competencies, play a crucial role as care providers for children in the emergency department, and ensure the comfort and safety of children seeking treatment. The categories related to child-friendly emergency care identified in this study can serve as a basis for developing child-friendly care emergency guidelines.
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Servicio de Urgencia en Hospital , Enfermeras y Enfermeros , Humanos , Investigación Cualitativa , Hospitales , TaiwánRESUMEN
OBJECTIVE: Protocadherin-19 (PCDH19) epilepsy is a rare female restricted epilepsy syndrome with early onset seizures and developmental delay caused by a change or mutation of the PCDH19 gene on the X chromosome. SCN1A-negative patients with a Dravet-like phenotype may have a gene mutation in PCDH19. The aim of this case series was to characterize the phenotype of epileptic patients according to PCDH19 mutations, antiseizure medications, brain images and mutation types in Taiwan. METHODS: We retrospectively reviewed the medical records of patients with PCDH19 epilepsy from July 2017 to December 2021 from multiple centers in Taiwan. We analyzed the patients' clinical data and genetic reports. RESULTS: Fifteen female patients (age 3-23 years) were enrolled. Seizure onset was at 4 months to 2 years 7 months of age with generalized tonic-clonic or focal seizures. Seizure frequency tended to be in clusters rather than single longer seizures. The patients had varying degrees of intellectual disability, however 3 had no impairment. Two patients had abnormal brain images including mesial temporal sclerosis, subcortical and periventricular white matter lesions. On average, the patients received 4 antiseizure medications (range 3-6), including 9 patients who were seizure free, and 3 who received sodium channel blockers without aggravation. Missense and truncating variants (frameshift and nonsense variants) accounted for 40% and 46.7% of all mutations. The mutations of 13 patients were located on EC1 to EC4, and EC5 to cytoplasmic domain in 2 patients. SIGNIFICANCE: PCDH19 epilepsy has distinct phenotypes and an unusual X-linked pattern of expression in which females manifest core symptoms. Psychiatric and behavioral problems are frequently part of the clinical picture. Patients are usually treated with a wide array of standard antiseizure medications, with no preferred antiseizure medication class. No strong correlations between phenotype and location of variant mutations were found in our patients.
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BACKGROUND: The role home-schooling of children in parental mental health during the COVID-19 pandemic in Taiwan remains unknown. This study aimed to assess the association between parental psychological distress and home-schooling in a socio-ecological context during the peak of the first wave of the COVID-19 pandemic in Taiwan. METHODS: This was a prospective cohort study. In total, 902 parents (father: n = 206, mother: n = 696) who home-schooled children under 18 years of age were recruited by purposive sampling from 17 cities in Taiwan. Data were collected between 19 July and 30 September 2021 through a survey. Multilevel regression models were used to examine the association between parents' psychological distress and home-schooling considering the characteristics at the person and city levels. RESULTS: Parental psychological distress was positively associated with difficulty in setting up electronic devices and increased disputes between parents and children, and it was negatively associated with time management and increased time spent bonding with their children during home-schooling (Ps < 0.05). Parents who had a child with health conditions, lived in an extended family, worked from home, lived during the Level 3 alert level, and lived with a median/sporadic level of the COVID-19 community spread by city also reported greater psychological distress (Ps < 0.05). However, parents who had greater household family support reported less psychological distress (P < .05). CONCLUSIONS: Clinicians and policy makers must carefully consider parental mental health while home-schooling during the COVID-19 pandemic in a broader socio-ecological context. A focus is advised on the home-schooling experiences of parents and other risk and protective factors for parental psychological distress at the person and city levels, especially for those with children who require medical interventions and have a medical condition.
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COVID-19 , Niño , Humanos , Adolescente , COVID-19/epidemiología , Taiwán/epidemiología , Factores Protectores , Pandemias , Estudios Prospectivos , Padres/psicologíaRESUMEN
Objective: To investigate the relationship between sleep problems and development in preschool children with suspected developmental delay. Methods: A total of 192 preschool children (mean age 4 years; 131 males, 61 females) were recruited from the Child Development Clinic, including 98 preterm children and 94 age- and sex-matched full-term children. All participants underwent evaluation of gross motor, fine motor and speech performance. All parents of all participants completed the Children's Sleep Habits Questionnaire (CSHQ). Some of the participants also underwent psychological evaluation. Correlation analysis and community network analysis were used to investigate the interactions. Results: The developmental status was: 75.5% developmental delay, 19.3% borderline development, and 5.2% normal development. Eighty-nine percent of the subjects had abnormal CSHQ scores. Age, gestational age, speech development, cognitive development, and socio-emotional development were significantly correlated with the CSHQ. Significant interactions between sleep problems and development were noted mostly in the preterm group. Conclusion: High prevalence of sleep disturbances in children at the Child Development Center was noted and associated with multiple factors. Therefore, during the multidisciplinary evaluation of children with possible developmental delay, inquiring about their sleep quality and habits is strongly recommended. Mitigating sleep problems enhances the efficacy of early intervention programs.
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PURPOSE: Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. METHODS: A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. KEY FINDINGS: One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. SIGNIFICANCE: We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients.
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Epilepsia/genética , Mutación/genética , Proteínas Serina-Treonina Quinasas/genética , Encéfalo/patología , Encéfalo/fisiopatología , Preescolar , Codón sin Sentido/genética , Variaciones en el Número de Copia de ADN/genética , Electroencefalografía , Epilepsia/patología , Epilepsia/fisiopatología , Femenino , Lóbulo Frontal/patología , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Mutación Missense/genética , Factores SexualesRESUMEN
Dravet syndrome (DS) is an uncommon epilepsy syndrome that may negatively affect the patients and their caregivers. However, reliable and valid measures of its impact on caregivers and the characteristics of patients with DS in Taiwan are lacking. This study aimed to describe the characteristics of patients with DS and concerns of their caregivers and establish a baseline frequency of disease characteristics using a cross-sectional survey in Taiwan. We assessed the caregivers of patients with DS using an online anonymous questionnaire. The seizure frequency decreased with age, although lacking statistical significance. Vaccines show no influence on the condition of patients with DS. Our findings revealed the highest impact on the domains affecting the caregivers' daily life, including additional household tasks, symptom observation, further medical plan, and financial issues. Caregivers also expressed concerns regarding the lack of independence/constant care, seizure control, speech/communication, and impacts on siblings because of long-term care of the patients in parents' absence. Our findings highlight the significant effects of caring for a child with DS on the lives of their caregivers in Taiwan; these findings will help raise awareness regarding the needs of these families. Furthermore, we discussed the possible pathophysiological mechanisms of associated comorbidities.
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Cuidadores/psicología , Epilepsias Mioclónicas/patología , Mutación , Canal de Sodio Activado por Voltaje NAV1.1/genética , Calidad de Vida/psicología , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Comorbilidad , Estudios Transversales , Epilepsias Mioclónicas/genética , Femenino , Humanos , Lactante , Masculino , Encuestas y Cuestionarios , Taiwán/epidemiología , Adulto JovenRESUMEN
Array-based comparative genomic hybridization identified a 2.3-Mb microdeletion of 17p13.2p13.1 in a boy presenting with moderate mental retardation, intractable epilepsy and dysmorphic features. This deletion region was overlapped with the previously proposed shortest region overlapped for microdeletion of 17p13.1 in patients with mental retardation, microcephaly, microretrognathia and abnormal magnetic resonance imaging (MRI) findings of cerebral white matter, in which at least 17 known genes are included. Among them, DLG4/PSD95, GPS2, GABARAP and KCTD11 have a function in neuronal development. Because of the functional importance, we paid attention to DLG4/PSD95 and GABARAP, and analyzed zebrafish in which the zebrafish homolog of human DLG4/PSD95 and GABARAP was knocked down and found that gabarap knockdown resulted in small head and hypoplastic mandible. This finding would be similar to the common findings of the patients with 17p13.1 deletions. Although there were no pathogenic mutations in DLG4/PSD95 or GABARAP in a cohort study with 142 patients with idiopathic developmental delay with/without epilepsy, further studies would be required for genes included in this region.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Portadoras/metabolismo , Cromosomas Humanos Par 17/genética , Técnicas de Silenciamiento del Gen , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Pez Cebra/metabolismo , Pez Cebra/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Animales , Proteínas Reguladoras de la Apoptosis , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Proteínas Portadoras/genética , Niño , Deleción Cromosómica , Análisis Citogenético , Análisis Mutacional de ADN , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Oligonucleótidos Antisentido/farmacología , Embarazo , Proteínas de Pez Cebra/genéticaRESUMEN
We performed STXBP1 mutation analyses in 86 patients with various types of epilepsies, including 10 patients with OS, 43 with West syndrome, 2 with Lennox-Gastaut syndrome, 12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 5 with other undetermined types of epilepsy. In all patients, the etiology was unknown, but ARX and CDKL5 mutations were negative in all cases. All coding exons of STXBP1 were analyzed by direct-sequencing. Two de novo nucleotide alterations of STXBP1 were identified in two patients with Ohtahara and West syndrome, respectively. No de novo or deleterious mutations in STXBP1 were found in the remaining 84 patients with various types of symptomatic epilepsies. This is the first case report showing that STXBP1 mutations caused West syndrome from the onset of epilepsy. STXBP1 analysis should be considered as an etiology of symptomatic West syndrome without explainable cause.
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Proteínas Munc18/genética , Mutación/genética , Espasmos Infantiles/genética , Pueblo Asiatico/genética , Niño , Estudios de Cohortes , Femenino , Haploinsuficiencia/genética , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Síndrome de Lennox-Gastaut , Masculino , Mutación Missense/genética , Espasmos Infantiles/diagnósticoRESUMEN
BACKGROUND: Cyclin-dependent kinase-like 5 (CDKL5), which maps to chromosome Xp22.13 and contains 20 coding exons, has been recognized as the gene responsible for early-onset epileptic encephalopathy (EoEE). A retrospective study is carried out to analyze potential genotypic and phenotypic differences between male and female patients with CDKL5 mutations. MATERIALS AND METHODS: Targeted next-generation DNA sequencing was employed to search for mutations in patients with cryptogenic EE. A total of 44 patients with EoEE/infantile spasms (ISs)/West syndrome were enrolled for pathogenic mutation screening. The clinical phenotypes of patients with CDKL5 mutations were analyzed and compared with those of 166 published cases. RESULTS: One novel and three recurrent mutations were found in four enrolled patients (two boys and two girls). One female patient had partial seizures during the early infantile period and epileptic spasms and tonic seizures several weeks thereafter. The other female patient had IS with hypsarrhythmia. The two male patients had IS without typical hypsarrhythmia and were bedridden. Brain MRIs of the male patients revealed brain atrophy and white matter hyperintensity. The female patients exhibited autistic features with hand stereotypies. CONCLUSION: Our study highlights that both girls and boys with IS harbor CDKL5 mutations. Male children with CDKL5 mutations demonstrate a higher frequency of infantile spasms and brain atrophy, whereas female children often exhibit atypical Rett syndrome with EoEE. In addition, male children have a more severe phenotype than female children.
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Mutación , Proteínas Serina-Treonina Quinasas/genética , Niño , Epilepsia/diagnóstico por imagen , Epilepsia/genética , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Hipotonía Muscular/genética , Fenotipo , Síndrome de Rett/genética , Factores SexualesRESUMEN
BACKGROUND: Epilepsy caused by a KCNQ2 gene mutation usually manifests as neonatal seizures during the first week of life. The genotypes and phenotypes of KCNQ2 mutations are noteworthy. METHODS: The KCNQ2 sequencings done were selected from 131 nonconsanguineous pediatric epileptic patients (age range: 2 days to 18 years) with nonlesional epilepsy. RESULTS: Seven (5%) index patients had verified KCNQ2 mutations: c.387+1 G>T (splicing), c.1741 C>T (p.Arg581*), c.740 C>T p.(Ser247Leu), c.853 C>A p.(Pro285Thr), c.860 C>T p.(Thr287Ile), c.1294 C>T p.(Arg432Cys), and c.1627 G>A p.(Val543Met). We found, after their paternity had been confirmed, that three patients had de novo p.(Ser247Leu), p.(Pro285Thr), and p.(Thr287Ile) mutations and neonatal-onset epileptic encephalopathy; however, their frequent seizures remitted after they turned 6 months old. Those with the c.387+1G>T (splicing), (p.Arg581*), and p.(Val543Met) mutations presented with benign familial neonatal convulsions. In addition to their relatives, 14 patients had documented KCNQ2 mutations, and 12 (86%) had neonatal seizures. The seizures of all five patients treated with oxcarbazepine remitted. CONCLUSION: KCNQ2-related epilepsy led to varied outcomes (from benign to severe) in our patients. KCNQ2 mutations accounted for 13% of patients with seizure onset before 2 months old in our study. KCNQ2 mutations can cause different phenotypes in children. p.(Pro 285Thr) is a novel mutation, and the p.(Pro 285Thr), p.(Ser247Leu), and p.(Thr287Ile) variants can cause neonatal-onset epileptic encephalopathy.
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Epilepsia/genética , Canal de Potasio KCNQ2/genética , Mutación Missense , Fenotipo , Adolescente , Ondas Encefálicas , Niño , Preescolar , Epilepsia/patología , Femenino , Humanos , Lactante , MasculinoRESUMEN
SCN2A mutations have been identified in various encephalopathy phenotypes, ranging from benign familial neonatal-infantile seizure (BFNIS) to more severe forms of epileptic encephalopathy such as Ohtahara syndrome or epilepsy of infancy with migrating focal seizure (EIMFS). Thus far, no particularly effective treatment is available for severe epileptic encephalopathy caused by SCN2A mutations in children. We present the case of a boy who developed seizures on the third day of life and received a diagnosis of EIMFS based on his clinical presentations and electroencephalography reports. Antiepileptic drugs, namely oxcarbazepine, phenytoin, valproate, levetiracetam, and clonazepam, as well as adrenocorticotropic hormone therapy failed to reduce the severity of the seizures. Seizure pattern changed to infantile spasm with extensor thrust since 5â¯months of age. A ketogenic diet consisting of a medium-chain triglyceride recipe was introduced at 8â¯months of age and the seizures were resolved in the following 10â¯months. A de novo mutation in SCN2A (c.573Gâ¯>â¯T; p.W191C) was proven through next-generation sequencing.
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Dieta Cetogénica , Epilepsia Refractaria/dietoterapia , Canal de Sodio Activado por Voltaje NAV1.2/genética , Convulsiones/dietoterapia , Espasmos Infantiles/dietoterapia , Encéfalo/fisiopatología , Epilepsia Refractaria/genética , Epilepsia Refractaria/fisiopatología , Humanos , Lactante , Masculino , Mutación , Convulsiones/genética , Convulsiones/fisiopatología , Espasmos Infantiles/genética , Espasmos Infantiles/fisiopatologíaRESUMEN
The trace element manganese is usually supplied when total parenteral nutrition is used. However, long-term parenteral administration of manganese, which bypasses the normal regulatory mechanism, may cause hypermanganesemia. Manganese poisoning presents clinically with parkinsonian-like symptoms and psychological changes. Seizures are a rare presentation of this disease. This report describes a 10-year-old female who had received total parenteral nutrition for 3 months because of short bowel syndrome, and presented with tonic-clonic seizure, decreased level of consciousness, and fever. The serum electrolytes, glucose and the cerebrospinal fluid examination were normal. The blood culture grew Pantoea agglomerans. The brain magnetic resonance imaging disclosed no evidence of central nervous system infection. However, symmetric high-intensity signal on T1-weighted images was documented in the basal ganglia, especially in the globus pallidus. Her whole blood manganese level was 3.7 microg/dL, which was significantly higher than the normal range (0.4-1.4 microg/dL). Diagnosis of hypermanganesemia related to total parenteral nutrition was made.