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Objective:To investigate the clinical phenotype and genetic characteristics of developmental epileptic encephalopathy 18 (DEE18) caused by SZT2 gene variants. Methods:Clinical data of 2 children with SZT2 related DEE18 who visited the Department of Pediatric Neurology, Linyi People′s Hospital in March 2020 and July 2023 were collected. The whole exome sequencing (WES) and Sanger sequencing were applied to verify the child and their parents. SWISS-MODEL software was used to perform protein 3D modeling for the selected SZT2 gene variants. Results:Both of the 2 cases showed severe global developmental delay, epileptic seizures, autism, megacephaly, facial deformity, hypotonia, corpus callosum malformation, persistent cavum septum pellucidum, and slow background activity and focal discharge in video electroencephalography. Case 1 was easy to startle and thin in stature; case 2 had immune deficiency and clustered seizures. WES results showed that case 1 carried a compound heterozygous variant of c.5811G>A (p.W1937X) (paternal) and c.9269delG (p.S3090Ifs *94) (maternal), while case 2 carried a compound heterozygous variant of c.6302A>C(p.H2101P) (paternal) and c.7584dupA (p.E2529Rfs *20) (maternal), the parents of both patients with normal clinical phenotypes. The 4 mutations mentioned above were novel variations that had not yet been reported domestically or internationally. According to the American College of Medical Genetics and Genomics variant classification criteria and guidelines, the p.S3090Ifs *94 variant was interpreted as pathogenic; p.W1937X variant was interpreted as pathogenic; p.E2529Rfs *20 variant was interpreted as likely pathogenic; p.H2101P variant was interpreted as uncertain significance. 3D modeling showed that the variant of p.H2101P resulted in a significant change in the hydrogen bond around the 2 101st amino acid encoded, leading to a decrease in protein stability. The other 3 variants led to early truncation of peptide chain and obvious changes in protein structure. Conclusions:DEE18 caused by SZT2 gene mutation is mainly an autosome recessive genetic disease, and its clinical manifestations include global developmental delay, epileptic seizures, autism, craniofacial malformation, hypotonia, epileptic discharge, corpus callosum malformation, persistent cavum septum pellucidum, shock, small and thin stature, and immune deficiency. Four novel variants related to the SZT2 gene may be the genetic etiology of DEE18 patients in this study.
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Objective:To explore the clinical manifestations and differential diagnosis of pituitary hyperplasia caused by primary hypothyroidism in children.Methods:A patient with pseudo-pituitary macroadenoma caused by hypothyroidism who received treatment in Hetian District People's Hospital, Xinjiang Uygur Autonomous Region, China was reported. Meanwhile, relevant literature was searched in Pubmed to sort out the clinical and imaging manifestations of pituitary hyperplasia caused by primary hypothyroidism and the differences from pituitary tumors.Results:This patient almost had to be surgically treated. After thyroid hormone replacement therapy, the growth and development of the patient recovered, and the pituitary gland was reduced.Conclusion:For patients with enlarged thyroid and pituitary glands, a comprehensive assessment and thyroid hormone replacement therapy are required. After follow-up for 3 months, re-evaluation is performed to determine whether there are indications for surgery to avoid permanent hypophyseal hypofunction caused by surgical resection.
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Objective To explore the content and the psychometric properties of assessment tools used for evaluating functioning and adaptive behavior in school-age children with intellectual and developmental disabilities within educational settings. Methods The most used assessment tools included Vineland Adaptive Behavior Scales(VABS),Supports Intensity Scale for Children(SIS-C),Strengths and Difficulties Questionnaire(SDQ)and Repetitive Behavior Scale-Revised(RBS-R),for assessing functioning and adaptive behavior children with intellectual and developmental disabili-ties.Employing the framework and methods of the International Classification of Functioning,Disability,and Health(ICF),this research encoded and categorized the assessment dimensions and items of the four tools,and explored their psychometric properties. Results VABS's assessment content was solely focused on activities and participation,including speaking(d330),con-versation(d350),toileting(d530),eating(d550),drinking(d560),basic interpersonal interactions(d710),com-plex interpersonal interactions(d720),changing and maintaining body positions(d410-d429),carrying,moving and handing objects(d430-d449),and walking and moving(d450-d469).SIS-C assessed activities and participa-tion,and environmental factors,including washing oneself(d510),caring for body parts(d520),community life(d910),using transportation(d470),school education(d820),basic learning(d130-d159),looking after one's health(d570),basic interpersonal interactions(d710),and products and technology for education(e130).SDQ fo-cused on body functions,and activities and participation,including emotional functions(b152),global psychoso-cial functions(b122),attention functions(b140),and basic interpersonal interactions(d710).RBS-R focused on body functions,and activities and participation,including involuntary movement reaction functions(b755),invol-untary movement functions(b765),looking after one's health(d570),energy and drive functions(b130),under-taking a single task(d210),carrying out daily routine(d230),attention functions(b140),and handling stress and other psychological demands(d240).VABS was characterized by good specificity and excellent sensitivity.SIS-C demonstrated very good internal consistency,reliability and validity.SDQ was good in internal consistency,with excellent credibility and validity.RBS-R showed good internal consistency,reliability and validity. Conclusion SDQ and RBS-R cover both body functions,and activities and participation,SIS-C covers activity and par-ticipation,and environmental factors,while VABS solely assesses activities and participation.In terms of body functions,the assessment items primarily focus on mental functions(b130-b189)and movement functions(b750-b799).For activities and participation,the tools assess content across eight domains of functioning.Regarding en-vironmental factors,the assessment content mainly includes products and technology for education(e130),as well as design,construction and building products and technology of buildings for public use(e150).VABS,SIS-C,SDQ,and RBS-R are all norm-referenced measures,with moderate to excellent internal consistency,and good to excellent reliability and validity.
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ObjectiveTo systematically review the benefits of digital empowerment technologies (DET) in promoting physical activity and health among children with intellectual and developmental disabilities (IDD). MethodsLiterature was retrieved from PubMed, Embase, Web of Science, PsycINFO and CNKI, for randomized controlled trials (RCT) published from 2014 to 2023 on the application of DET in physical activity among children with IDD. The quality was assessed, and high-quality RCT was systematically reviewed. ResultsEight high-quality RCT were included, originating from four countries, namely China, the United States, Italy and South Korea, with 376 children with IDD, main published in the journals about intellectual disability applications, developmental disability research and clinical medicine, from 2018 to 2023. The children aged seven to 18 years, suffered from intellectual disabilities (including Down syndrome), autism and other developmental disabilities. The technologies could be summarized in wearable technology, cloud computing guided and monitored by mobile health, virtual reality and augmented reality, and active video gaming technologies. The devices involved active video games, Fitbit smart devices, Wii Fit balance games, Stepmania rhythm video games, Xbox Kinect system, VZFit sensors and CoTras cognitive rehabilitation computer games. The virtual physical activities included boxing, track and field, bowling, table tennis, beach volleyball, football, baseball, skiing, tennis, golf, darts, American football, shooting, jumping, jogging and jump rope; 20 to 45 minutes a time, one to five times a week, for four to twelve weeks. The interventions could be conducted in homes, special education schools and rehabilitation institutions. The health benefits mainly reflected in improved levels of physical activity, enhanced motor function and increased motor and daily life capacity. ConclusionApplication of DET in physical activity may increase the participation of children with IDD in virtual environments, schools, communities and rehabilitation institutions; improve upper and lower limb motor function, gross motor function, and muscle strength; enhance static balance, motor coordination and sensorimotor function; reduce the sedentary behavior; and improve cognitive, daily living skills and social abilities.
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ObjectiveTo synthesize evidence from systematic reviews on the positive impacts of music interventions on the functioning, health and development of children and adolescents with intellectual and developmental disabilities (IDD). MethodsLiterature was searched across databases including PubMed, EBSCO, PsycINFO, Embase, Web of Science and CNKI, focusing on high-quality systematic reviews published from January, 2014 to March, 2024. These reviews examined the functioning, health and developmental benefits of music interventions (including therapy and education) for children and adolescents with IDD. ResultsEight English systematic reviews were included, involving 5 308 children and adolescents with IDD, from China, France, Spain, Canada, the United States and the United Kingdom; mainly from journals in the fields of music therapy, children and adolescents psychiatry, educational psychology, intellectual disability, autism spectrum disorder (ASD) and health psychology, mainly published between 2018 and 2023. The music therapy interventions mainly included music education interventions, improvisation music therapy (creation and performance), interactive music therapy (music and movement), mixed music therapy (including singing, dancing and drama), auditory-motor mapping training, family music therapy and melody-based communication therapy; involving basic music theory learning, music gesture and language training, music appreciation, improvisation, music ensemble, music cooperative games, etc; ten to 90 minutes a time, one to five times a week, for one to 32 weeks. In terms of cognitive development, music education interventions were beneficial for improving attention in children and adolescents with IDD. In terms of psycholinguistic skills, music therapy could significantly improve the articulation and language abilities of children and adolescents with ASD, especially phonological memory, word and sentence comprehension; and language and communication skills of children and adolescents with IDD, and enhance oral expression abilities. Music could also help improve behavioral disorders, including improving physical coordination, reducing repetitive behaviors and controlling hyperactive behaviors. In terms of music education performance, music therapy could improve amiliarity with song rhythm and melody, phoneme discrimination, mastering songs and lyrics, and enhance music rhythm perception of children and adolescents with IDD. In addition, music therapy also promoted social and emotional development, improved prosocial behavior and social skills, helped reduce anxiety, enhance emotional control, improve social skills and self-esteem, increase positive emotions, and strengthen communication and cooperation with peers and teachers. ConclusionMusic intervention has a positive impact on the function, health and development of children and adolescents with IDD, which is reflected in cognitive development, psycholinguistic skills, motor skills, music education performance, and children and adolescents' social and emotional development.
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Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach.
El síndrome de X frágil es causado por la expansión de tripletas CGG en el gen FMR1, el cual genera cambios epigenéticos que silencian su expresión. La ausencia de la proteína codificada por este gen, la FMRP, causa disfunción celular, llevando a deficiencia en el desarrollo cerebral y anormalidades funcionales. Las manifestaciones físicas y neurológicas de la enfermedad aparecen en edades tempranas y pueden sugerir el diagnóstico. Sin embargo, este debe ser confirmado por pruebas moleculares. El síndrome afecta múltiples aspectos de la vida diaria y representa una alta carga para los individuos afectados y para sus familias. El síndrome de C frágil es la causa monogénica más común de discapacidad intelectual y trastornos del espectro autista; por ende, el diagnóstico debe sospecharse en todo paciente con retraso del neurodesarrollo. Intervenciones tempranas podrían mejorar el pronóstico funcional de pacientes con síndrome de X frágil, impactando significativamente su calidad de vida y funcionamiento. Por lo tanto, la atención en salud de niños con síndrome de X frágil debe incluir un abordaje multidisciplinario.
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Introduction: Disability is a generic term that includes deficits, limitations in activity and restrictions in participation indicate the negative aspects of the interaction between an individual and its contextual factors, environmental and personal factors. Objective: The objective of this study was to identify the characteristics of labor inclusion and health-related quality of life of people with disabilities in a population group from the city of Neiva (Colombia). Materials and methods: Descriptive, analytical, cross-sectional study with quantitative approach and non-experimental design, in a sample of 64 people with disabilities. Demographic variables such as age, sex, marital status, education, socioeconomic status, link to the social security system in health, and type of disability were considered. The WHOQOL-BREF, 2004 quality of life scale was applied. Central tendency measures were also calculated with their dispersions and 95% confidence intervals in the continuous quantitative variables. Results: The most frequent disability was physical with 78.13%, followed by visual with 17.18%. The highest percentage of impairment of the quality of life concerning disability is given by the need to move from one place to another, to feel dissatisfaction with their sexual life and the perception of an unhealthy environment. Conclusions: The main factors for the labor inclusion of a person with a disability are subject to sex, the type of disability, access to decent employment, and remuneration according to their potentialities.
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Introducción: Es importante conocer el desarrollo psicomotor de los niños con parálisis cerebral de acuerdo con sus características sociodemográficas y clínicas para realizar un mejor tratamiento en este tipo de pacientes. Objetivo: Describir el desarrollo psicomotor según las características sociodemográficas y clínicas de niños hasta 36 meses con parálisis cerebral. Métodos: Estudio observacional, descriptivo, de corte transversal con datos retrospectivos. Se revisaron 177 historias clínicas de pacientes con diagnóstico de parálisis cerebral de 0 a 36 meses, atendidos del 1 de enero de 2015 al 31 de diciembre de 2016 en un instituto nacional de rehabilitación de Lima, Perú. Resultados: La edad promedio fue 25,1 ± 7,16 meses, el 58,19 % fue del sexo masculino, el grupo etario de 25-36 meses representó el 67,89 %, predominó la parálisis cerebral espástica cuadripléjica con 28,25 %, el 14,12 % tenía alteración en la audición y el 19,21 % convulsiones. El promedio de porcentajes de desarrollo psicomotor global fue de 62,66 %; los menores promedios fueron para el comportamiento motor grueso (57,15 %), el grupo etario de 0 a 12 meses (51,49 %), las niñas (57,72 %), la parálisis cerebral espástica cuadriplejia (42,55 %), niños con alteración auditiva y visual (36,92 %), con convulsiones (46,17 %) y prematuros (58,26 %). Conclusiones: Los niños hasta 36 meses con parálisis cerebral tienen un retraso global del desarrollo psicomotor de aproximadamente el 35 %, con mayor afectación los de menor edad, las niñas, los que tienen parálisis cerebral espástica cuadripléjica, alteración auditiva y visual, convulsiones y son prematuros.
Introduction: It is important to know the psychomotor development of children with cerebral palsy according to their sociodemographic and clinical characteristics to carry out a better approach in this type of patients. Objective: To describe the psychomotor development according to sociodemographic and clinical characteristics of children up to 36 months with cerebral palsy. Methods: Observational, descriptive, cross-sectional study with retrospective data. 177 medical records of patients with a diagnosis of cerebral palsy from 0 to 36 months were reviewed, treated from January 1, 2015 to December 31, 2016 at a national rehabilitation institute in Lima, Peru. Results: The average age was 25.1 ± 7.16 months, the 58.19% were male, the age group of 25-36 months represented 67.89%, quadriplegic spastic cerebral palsy predominated with 28.25%, 14.12% had alteration in hearing and 19.21% seizures. The average percentage of global psychomotor development was 62.66%; the lowest averages were for gross motor behavior (57.15%), the age group from 0 to 12 months (51.49%), girls (57.72%), spastic cerebral palsy quadriplegia (42.55%), children with hearing and visual impairment (36.92%), with seizures (46.17%) and premature (58.26%). Conclusions: Children up to 36 months with cerebral palsy have a global delay in psychomotor development of approximately 35%, with greater affectation in younger children, girls, those with spastic quadriplegic cerebral palsy, hearing and visual disorders, seizures and are premature.
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Abstract Background: Child development is a complex biological, psychological, and emotional process. Timely screening for developmental delay allows early interventions. Therefore, this study sought to assess the frequency and characteristics of developmental delay in children < 5 years of age who attended the Pediatric Rehabilitation Service of a referral hospital in Peru. Methods: We conducted a cross-sectional study. Information was collected from medical records of children < 5 years of age who attended between April and September 2022 at the Rebagliati Hospital's Pediatric Rehabilitation Service. The REBA-PED Child Developmental Assessment Profile was used for the developmental assessment, which allows to identify the degree of delay in each area (gross motor, fine motor, hearing and language, intelligence and learning, and personal-social) and the presence of warning signs. Results: Of 226 children who attended the service, 49.1% were between 3 and 5 years old, 57.1% were female, only 3.1% were referred for suspected developmental delay, and none had had a previous developmental assessment. Among the children evaluated, 12.4% had a simple developmental delay, 19.5% had a significant developmental delay, and 53.5% had a global developmental delay. In addition, 70.8% presented a warning sign of developmental delay. Hearing and language (86.8%) and intelligence and learning (83.5%) areas had a higher frequency of significant developmental delay. Conclusions: We found a high frequency of developmental delay in the children assessed, predominantly in hearing and language. Although all the children were referred, none had had a previous developmental assessment.
Resumen Introducción: El desarrollo infantil es un proceso complejo de cambios biológicos, psicológicos y emocionales. El despistaje oportuno del retraso del desarrollo permite implementar intervenciones tempranas. Este estudio buscó evaluar la frecuencia y las características del retraso del desarrollo en niños < 5 años atendidos en el Servicio de Rehabilitación Pediátrica de un hospital de referencia de Perú. Métodos: Se llevó a cabo un estudio transversal en el que se recolectó información de niños < 5 años atendidos entre abril y septiembre del 2022 en el Servicio de Rehabilitación Pediátrica del Hospital Rebagliati, para lo cual se revisaron sus historias clínicas. Para la evaluación del desarrollo, se utilizó el Perfil de Evaluación del Desarrollo Infantil REBA-PED, que permite reconocer el grado de retraso por área (motora gruesa, motora fina, audición y lenguaje, inteligencia y aprendizaje, y personal social) y los signos de alarma. Resultados: De 226 niños atendidos, el 49.1% tenía entre 3 a 5 años, el 57.1% era de sexo femenino, solo el 3.1% fue remitido por sospecha de retraso del desarrollo y ninguno había tenido una evaluación previa del desarrollo infantil. Entre los niños evaluados, el 12.4% presentó un retraso simple del desarrollo, el 19.5% presentó un retraso significativo y el 53.5%, un retraso global. Además, el 70.8% presentó algún signo de alarma durante el desarrollo infantil. La frecuencia de retraso significativo fue mayor en las áreas de audición y lenguaje (86.8%) y de inteligencia y aprendizaje (83.5%) tuvieron mayor frecuencia de retraso significativo. Conclusiones: Se encontró una frecuencia elevada de retraso del desarrollo entre los niños evaluados, con predominio del área de audición y lenguaje. Si bien todos los niños fueron referidos, ninguno había tenido una evaluación previa del desarrollo.
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Resumen En el actual escenario sociosanitario enfrentado a raíz de la pandemia por SARS-CoV-2, múltiples actividades se han visto mermadas, e incluso, suspendidas por los largos periodos de aislamiento social y las medidas de cuidado para evitar contagios. En este sentido, muchas personas han dejado de recibir con la misma regularidad, o bajo las mismas circunstancias, sus tratamientos, incluyendo a niños con Trastornos del Neurodesarrollo (TND). Es así como surgen las intervenciones Parentales. Estas son programas donde los padres o cuidadores primarios son entrenados para llevar a cabo acciones terapéuticas con el niño y cuyo objetivo puede estar orientado a promover múltiples habilidades. El objetivo de la presente revisión sistemática fue determinar el efecto de estas intervenciones para promover el lenguaje y la comunicación en niños con diagnóstico de TND de entre 2 y 5 años. Se realizó una búsqueda sistemática en las bases de datos ERIC, MEDLINE y PubMed, considerando publicaciones de entre enero del 2010 y marzo de 2022. De las 9885 referencias iniciales, y posterior a las etapas de tamizaje y elegibilidad, 5 fuentes primarias cumplieron con los criterios de selección. Los resultados indican que las intervenciones parentales para habilidades de comunicación serían efectivas e incluso se mantendrían los efectos en medidas de seguimiento. En cuanto a las habilidades de lenguaje, los resultados a través de los estudios son contradictorios. Por otra parte, ninguno de los estudios reporta efectos adversos para los niños. En cuanto a efectos beneficios o adversos para padres o cuidadores primarios, ninguno de los estudios incluidos reporta medidas asociadas.
Abstract In the current socio-sanitary scenario that we are facing as a result of the SARS-CoV-2 Pandemic, there have been many activities that have been reduced and even suspended due to long periods of social isolation and care measures to avoid contagion. In this sense, many people have stopped receiving their treatments with the same regularity or under the same circumstances, including children with Neurodevelopmental Disorders. This is how parental interventions correspond to programs where parents or primary caregivers are trained to carry out therapeutic actions with the child and whose objective may be aimed at promoting multiple skills. The objective of this systematic review was to determine the effect of these interventions to promote language and communication in children diagnosed with Neurodevelopmental Disorders between 2 and 5 years of age. A systematic search was carried out in the ERIC, MEDLINE and PubMed databases including publications between January 2010 and March 2022. Of the 9885 initial references, and after the screening and eligibility stages, 5 primary sources met the selection criteria. The results indicate that parental interventions for communication skills would be effective, and the effects would even be maintained in follow-up measures. Regarding language skills, the results across studies are contradictory. On the other hand, none of the studies reported adverse effects for children. Regarding beneficial or adverse effects for parents or primary caregivers, none of the included studies reported associated measures.
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Humanos , Masculino , Feminino , Pré-Escolar , Pré-Escolar/educação , Comunicação , Transtornos do Neurodesenvolvimento/diagnóstico , Desenvolvimento da Linguagem , Ensino de Recuperação , Desenvolvimento Infantil , Apoio FamiliarRESUMO
Introducción: Los potenciales evocados visuales (PEV) evalúan la vía visual mediante pequeñas respuestas neuroeléctricas de la corteza occipital. Constituyen un examen no invasivo para determinar la función visual en prematuros, recién nacidos, lactantes, niños con malformaciones cerebrales enfermedades metabólicas o retraso mental. Objetivo: Describir las características clínicas y los resultados de los Potenciales Evocados Visuales por Flash en niños menores de 5 años en el periodo de diciembre de 2017 a diciembre de 2018. Materiales y Métodos: Diseño observacional, descriptivo, ambispectivo con componente analítico. Los pacientes incluidos niños de 0 a 5 años de edad que se realizaron PEV en el Hospital Pediátrico en el período de diciembre de 2017 a diciembre de 2018. Muestreo no probabilístico de casos consecutivos. Variables principales: Edad, sexo, procedencia, profesional que solicitó el estudio, motivo de solicitud del estudio, datos maternos y perinatales, resultados del PEV. Los datos fueron analizados con SPSSv 21, utilizando estadística descriptiva. Resultados: Se estudiaron 110 pacientes que se realizaron PEV, la mediana de edad fue de 32 meses, predominó el sexo masculino, procedieron del departamento Central (63,6%). La mayoría de los pacientes presentaban Parálisis cerebral infantil (PCI), los neurólogos solicitaron mayormente el estudio. De los antecedentes perinatales, se evidenció que, a menor edad gestacional, menor peso de nacimiento, menor Apgar y antecedente de hospitalización perinatal, los valores de latencia y amplitud para la onda P100 en ambos ojos presentaban alteraciones, siendo esta relación estadísticamente significativa. Conclusión: Aunque en su mayoría los resultados de PEV fueron normales existe una relación importante entre los antecedentes perinatales y la alteración del resultado especialmente con respecto al Apgar a los 1 min mostrando una relación inversa.
Introduction: Visual evoked potentials (VEP) evaluate the visual pathway through small neuroelectric responses from the occipital cortex. They constitute a non-invasive test to determine visual function in premature babies, newborns, infants, children with brain malformations, metabolic diseases or mental retardation. Objective: To describe the clinical characteristics and the results of Flash Visual Evoked Potentials in children under 5 years of age during the time period from December 2017 to December 2018. Materials and Methods: This was an observational, descriptive and ambispective design with an analytical component. The patients included children from 0 to 5 years of age who underwent VEP at the Pediatric Hospital in the period from December 2017 to December 2018. We used non-probabilistic sampling of consecutive cases. Main variables: Age, sex, place of residence, professional who requested the study, reason for requesting the study, maternal and perinatal data, VEP results. Data were analyzed with SPSSv 21, using descriptive statistics. Results: 110 patients who underwent VEP were studied, the median age was 32 months, the male sex predominated, most lived in the Central department (63.6%). Most of the patients had infantile cerebral palsy (ICP), neurologists most frequently requested the study. Using the perinatal history, we determined that a lower gestational age, lower birth weight, lower Apgar score, and a history of perinatal hospitalization were associated with alterations in the latency and amplitude values for the P100 wave in both eyes, this relationship was statistically significant. Conclusion: Although the majority of the VEP results were normal, there is an important relationship between the perinatal history and the alteration of the result, especially with respect to the Apgar at 1 min, which shows an inverse relationship.
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Objective:To analyze the clinical and genetic features of the children with 5p15.1-5p15.33 duplication at the end of the short arm of chromosome 5 (5p).Methods:Clinical data of a 5p15.1-5p15.33 duplicative patient diagnosed in the Department of Pediatric Intensive Care Unit of West China Second University Hospital of Sichuan University in July 2021 were collected, and the characteristics of the patients of 5p duplication syndrome reported in the literatures were summarized and analyzed.Results:The boy was 1 year and 5 months old at the time of admission. The main clinical manifestations included growth restriction and developmental delay after birth, accompanied by craniofacial deformities. At 7 months old, he was diagnosed as epilepsy due to convulsive limbs. At present, he is 2 years old, still has recurrent convulsions, can not raise his head, sit alone, crawl and talk, with hypotonia. Repeated cranial magnetic resonance imaging showed agenesis of the corpus callosum. The child′s parents had normal phenotypes. His copy number variation sequencing results showed partial overlap of chromosome 5p15.1-5p15.33 (chr5:1934522-18905656), which was determined as pathogenic copy number variation according to copy number variations evaluation criteria, and no abnormality was detected in his parents. According to the retrieval strategy set in this study, 10 literatures (all in English, reporting 17 cases) were retrieved, and a total of 22 5p duplication syndrome patients (including this case and 4 cases included in databases) were included. Seventeen of the 22 patients were younger than 14 years old with a onset age of 7 (0, 18) years, and the male to female ratio was about 1.1∶1. Among the 22 patients, craniofacial malformation was found in 19 patients, developmental disorder in 18, bone/muscle dysplasia in 15, autism in 11, attention deficit hyperactivity disorder in 9, mental retardation in 8, obesity in 5, epilepsy in 5, congenital heart dysplasia in 2, hypotonia in 4, strabismus/hyperopia in 2, and corpus callosum dysplasia, endocrine dysfunction, inguinal hernia as well as umbilical hernia in 1, respectively. There were 19 cases of multiple malformation and 3 cases of single malformation.Conclusions:5p15.1-5p15.33 duplication may be the genetic cause of this child. Facial malformation, developmental delay, skeletal/muscular dysplasia, intellectual disability, autism spectrum disorder and attention deficit hyperactivity disorder are the main clinical phenotypes of 5p copy number duplication. Corpus callosum dysplasia may be an extended phenotype of chromosome duplication at this location.
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Objective:To investigate the clinical phenotype and gene mutation in a child with developmental disorders caused by CTNNB1 gene mutation. Methods:Clinical data of a child with CTNNB1 gene mutation who was admitted to Xiamen Hospital of Fudan University Affiliated Pediatric Hospital in May 2017 were collected, whole exome sequencing technology was applied to verify the family lineage of the child, and the pathogenicity of mutation site was analyzed. Results:The patient was a 6 years and 1 month old male, with a clinical phenotype including mental retardation, motor developmental disorders, speech disorders, visual disorders (internal strabismus), microcephaly, and behavioral problems (social withdrawal, overdependence, etc.), as well as panic syndrome (i.e., sudden shrieking in response to auditory and visual stimuli, extensional rigidity of the body, etc., followed by short periods of general extensional rigidity). The whole exome sequencing results showed the presence of a de novo mutation c.283(exon4)C>T in the CTNNB1 gene, and the c.283(exon4)C>T mutation was interpreted as pathogenic (PVS1+PS2+PS1+PM2+PM) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. No relevant genetic variants were found in the parental family verification. Conclusion:CTNNB1 gene mutation c.283(exon4)C>T can cause neurodevelopmental disorders, including mental retardation, motor developmental disorders, speech disorders, visual disorders, microcephaly and behavioral abnormalities.
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Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.
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This article reported the prenatal diagnosis of a fetus with ZTTK syndrome. A pregnant woman underwent preimplantation genetic diagnosis because her partner carried a balanced chromosomal translocation. Chromosomal karyotype analysis and copy number variation sequencing (CNV-seq) performed on amniocytes collected at 18 + weeks of gestation revealed no abnormalities. Ultrasonography performed at 23 +5 and 26 +3 weeks of gestation revealed severe fetal growth restriction, cerebellar dysplasia, poorly visualized sacrum and coccyx, and spina bifida. MRI of the fetal brain showed that the bilateral cerebellar hemispheres of the fetus were small and the cisterna magna was large at 23 +6 weeks of gestation. Whole exome sequencing in the pedigree identified a heterozygous variant c.2092delG (p.Glu698fs*4) in the exon 3 of the fetal SON gene, which was not inherited from the parents and proved to be a de novo mutation. Mutations in the locus are pathogenic, causing ZTTK syndrome. After genetic counseling, the pregnant woman and her family chose to terminate the pregnancy.
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This article reported a male patient with neonatal onset mental retardation autosomal dominant 35 (MRD35). The boy presented with repeated convulsions, hypotonia, enlarged head circumference, congenital muscular torticollis and feeding difficulties in the neonatal period. Dynamic electroencephalogram showed paroxysmal epileptic discharges in the left central-temporal region. High-throughput whole-exome sequencing revealed a heterozygous mutation of c.139G>A (p.Glu47Lys) in the PPP2R5D gene, which was a de novo mutation not inherited from his parents. The child had significant developmental delay at the age of one year. MRD35 lacks typical clinical manifestations and requires whole-exome sequencing for definitive diagnosis. Currently, there is no specific treatment for MRD35 and symptomatic treatments, including rehabilitation training, language training and seizure control, are mostly adopted.
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Global developmental delay/intellectual disability (GDD/ID) is an enormous group of neurodevelopmental disorders with diverse clinical and genetic heterogeneity. The estimated prevalence of GDD/ID was 1%-3%, affecting about 150 million people. GDD/ID is one of the leading causes of disability in children worldwide. The causes of GDD/ID are complex, comprising genetic and environmental factors. It is often co-morbid with a variety of psychiatric behavioral disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Owing to the improvement of genetic technology, monogenic GDD/ID has been one of the hot-spot research in genomic era, and the relevant preventive measures deserve extensive attention. In this review, we summarized the advances in genetics and prevention of monogenic GDD/ID.
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Atypical absences are generalized non-motor epileptic seizures which are one of the characteristics of developmental epileptic encephalopathy, and are typically affecting patients with cognitive and intellectual disabilities. Compared with typical absence seizures, the pathogenesis, etiology, electro-clinical characteristics, treatment, and prognosis of atypical absence seizures are more complex. This article aims to summarize the clinical characteristics and etiological research progress of atypical absence seizures, to increase clinicians′ awareness of them and provide new ideas for etiology-based diagnosis and treatment.
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Objective:To summarize the clinical phenotype and genetic characteristics of biallelic variation in HPDL leading to neurodevelopmental disorders with progressive spasticity and cerebral white matter abnormalities. Methods:The clinical and genetic data of 3 cases with neurodevelopmental disorders confirmed in the Department of Neurology of the Affiliated Children′s Hospital of Zhengzhou University from February 2018 to June 2022 were analyzed. The second-generation sequencing method was used to sequence the HPDL gene and the first-generation Sanger sequencing was used to verify the family members, and the characteristics of gene variants were summarized, and the 3 cases were treateds and followed-up. Results:Among the 3 children with neurodevelopmental disorders, 2 were females and 1 was male, and the age of onset was 25 days to 11 years of birth. In the clinical phenotypes, cases 1 and 2 were children with Leigh-like syndrome with infancy onset, with recurrent seizures, intelligent backwardness, language and motor delay, lactic acid increase, acidosis. Cranial magnetic resonance plain scan suggested deepening of the sulcus in the bilateral cerebral hemisphere, abnormal symmetrical signals in the basal ganglia, dorsal thalamus, cerebral peduncles and brainstem, expansion of the supratentorial ventricle, and thinning of the corpus callosum. And cranial magnetic resonance spectroscopy suggested visible lactate peaks in the measurement area of bilateral putamen lesions. Case 3 presented with spastic paraplegia, early motor retardation, and late spastic gait. The plain skull magnetic resonance imaging scan showed no abnormalities. In the 3 cases, the whole exon genome sequencing showed the heterozygous variant c.26_.28delGCC(p.Cys9_His10delinsTyr) and the parent missense heterozygous variant c.788C>T(p.Thr263Met), the paternal truncated variant c.1051C>T(p.Gln351 *) and the parent frameshift variant c.995de1C(p.Thr332Mfs * 9), the parent missense variant c.781C>G (p.Leu261Val) and the parent truncated variant c.721C>T (p.Gln241 *). The c.26_28delGCC(p.Cys9_His10delinsTyr) was an unreported site mutation. No abnormalities were found in chromosomal copy number variation and mitochondria-related genes. Cases 1 and 2 were treated with anti-seizure drugs and cocktail, and the seizure was under effective control; case 3 was treated with comprehensive treatment and rehabilitation function training, and exercise and intelligence were improved. Conclusions:The clinical phenotype of the biallelic variant in HPDL was Leigh-like syndrome and hereditary spastic paraplegia, characterized by compound heterozygous variant, including whole code, missense, frameshift, and truncated variants. Biallelic variation in HPDL was found to be the genetic etiology of the 3 probands.
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Objective:To explore the genetic causes of cerebellar hypoplasia (CH) diagnosed by prenatal ultrasound.Methods:This retrospective study involved 32 fetuses with CH diagnosed by prenatal ultrasound in Wuxi Maternal and Child Health Hospital from January 2014 to December 2022. Prenatal ultrasound findings and genetic testing results for amniotic fluid were collected and analyzed. The correlation between fetal CH and genetic abnormality was analyzed. A descriptive statistical method was used for data analysis.Results:(1) General data: The 32 mothers were (28.0±4.9) years old, ranging from 18 to 37 years old; the gestational age at amniocentesis was (24.2±4.0) weeks, ranging from 18 +3 weeks to 37 +2 weeks. Apart from one case lost to follow-up, the other 31 cases terminated the pregnancies, including 30 terminated before 28 weeks of gestation and one at 33 weeks of gestation due to unmarried status. (2) Ultrasonic features: Among the 32 cases, 30(93.8%) were complicated by intracranial or extracranial abnormalities including cardiac abnormalities (15 cases), dilated lateral ventricles (ten cases), and abnormalities in limbs (eight cases) and face (nine cases). Two CH cases (6.2%) were isolated. (3) Genetic testing: Among the 32 cases, 13 cases (40.6%) had normal results of amniotic fluid karyotype analysis and single nucleotide polymorphism (SNP) array. Among the 19 cases with abnormal amniotic fluid test results (59.4%), 16 cases have abnormal results in amniotic fluid karyotype analysis and SNP array detection [nine cases were numerical abnormalities, including five cases of trisomy-18, three of trisomy-21, and one of trisomy-13; seven cases were chromosomal structural abnormalities, including four cases of terminal deletion of chromosome 5 (Cri-du-Chat syndrome) and three cases of reciprocal translocation of chromosomes]. There was no abnormality in karyotype analysis of amniotic fluid in three cases. Still, their SNP array test results showed copy number variations (CNV) [one of 6q terminal deletion, one of 6q terminal deletion with 5p15.33 duplication, and one of 6q terminal deletion with 15q26.3 duplication; all variations were of unknown significance]. (4) Of the 19 cases with abnormal SNP array results, 17 were accompanied by abnormal intracranial/extracranial ultrasound findings. Among them, ten cases showed cardiac malformation, seven showed lateral ventricular widening, and seven showed limb abnormality. Conclusions:Numerical abnormalities, CDCS, and 6q terminal deletion are the most common genetic causes of CH diagnosed by prenatal ultrasound. Chromosome microarray analysis should be recommended for fetuses with ultrasound-diagnosed CH to evaluate fetal prognosis accurately.