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Objective:To summarize the clinical phenotype and genetic characteristics of children with neurodegeneration caused by UBTF gene mutations in childhood. Methods:The clinical and genetic data of 3 children with neurodegeneration in childhood diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University from February 2020 to January 2023 were retrospectively analyzed. All the 3 probands were found having UBTF gene mutations through the whole exome gene sequencing, and the first generation Sanger sequencing method was used to verify the UBTF gene in their family members. The variation characteristics of the UBTF gene were analyzed, and the treatment and follow-up results of the 3 children were summarized. Results:Among the 3 children with childhood onset neurodegeneration, 2 were male and 1 female, aged 9 months, 4 years and 6 months after birth, respectively. The clinical phenotypes mainly included motor retardation, speech and mental retardation, and dystonia. Among them, case 1 and case 2 had seizures, case 1 had dysphagia, feeding problems, no weight gain and ataxia. Brain MRI plain scan showed that case 1 and case 2 had different degrees of cerebral atrophy, case 1 had hypoplasia of corpus callosum, ventricle expansion and softening focus, and case 3 showed non-specific widening of the subarachnoid space. There were no abnormalities in the chromosome copy number variation and mitochondrial ring gene testing in the 3 children; the whole exon gene testing suggested the de novo missense variant in the UBTF gene [NM_014233.4: c.1414(exon14) G>A (p.Gly472Ser), c.1392(exon14)G>T(p.Lys464Asn)] and the maternal nonsense variant [NM_014233.4:c.520C>T(p.Arg174 *)], which were unreported site variants. In terms of treatment, the 3 children received comprehensive rehabilitation function training, and achieved a certain degree of language and intelligence improvement. Seizure control was effectively managed in case 1 with a single antiepileptic drug. Epileptic seizures were effectively treated and controlled in case 2 using more than 4 types of antiepileptic drugs. Conclusions:Neurodegenerative changes caused by UBTF gene mutations in childhood are relatively rare, and some cases may be accompanied with brain atrophy. De novo missense variation and maternal nonsense variation of the UBTF gene are the genetic etiology of the 3 probands.
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【Objective】 To explore the effect of physical fitness training on social adaptive behavior of children with global developmental delay (GDD), in order to provide treatment experience for GDD children. 【Methods】 From November 2021 to December 2022, a total of 60 children with GDD diagnosed and treated in the Third Affiliated Hospital of Jiamusi University were enrolled in this study, and were randomly divided into control group (n=30) and test group (n=30).The control group received routine rehabilitation treatment, and the test group received physical fitness training additionally.The intervention lasted for 12 weeks, with the frequency of 3times/week, 30min/time.All subjects were tested for physical fitness and children′s social adaptive behavior before and after training. 【Results】 Before treatment, the difference between the results of physical fitness test and social adaptive behavior scores of the GDD children in two groups was not statistically significant (P>0.05).After 3 months of treatment, the physical fitness test scores, except body mass index (BMI), and social adaptive behavior scores of the GDD children in two groups were significantly different from those before treatment (P<0.05), and the physical fitness test scores (except for height, weight and BMI) and the social adaptive behavior of the test group were better than those of the control group (t=2.363,4.020,3.331,3.338,P<0.05). 【Conclusion】 Physical fitness training can significantly improve the adaptive behavior, independent function, cognitive function and social/self-control ability of GDD children.
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Objective To measure and compare the cerebral blood flow(CBF)of children with autism spectrum disorder(ASD),global developmental delay(GDD),and ASD with GDD groups via arterial spin labeling(ASL)technique,and to evaluate the diag-nostic value of CBF values.Methods ASL images of ASD,GDD,and ASD with GDD groups of children were firstly acquired,and the CBF values of frontal lobe,temporal lobe,parietal lobe,occipital lobe,striatum and thalamus region of interest(ROI)were fur-ther measured,respectively.One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences in CBF values among these three groups,and the receiver operating characteristic(ROC)curve was used to analyze the efficacy of CBF values in distinguishing ASD with GDD from without GDD.Results ASD with GDD had significantly lower CBF values in the left and right frontal lobes than those with ASD or GDD alone,and the differences were statistically significant(P<0.05).The CBF values in the left and right frontal lobes effectively distinguished ASD with GDD from without GDD[area under the curve(AUC)>0.7].Conclusion ASL technique can noninvasively assess CBF in children with or without GDD,helping to understand the pathophysiology of ASD with GDD and improving diagnostic accuracy.
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Se presenta un niño de 6 años con antecedente de retraso del lenguaje que llevó a sus padres a realizar múltiples consultas. En un primer momento, su cuadro fue interpretado como parte de un retraso global del desarrollo. Posteriormente, el paciente presentó convulsiones y episodios de descompensación metabólica, comenzando desde entonces su seguimiento por los Servicios de neurología, genética y metabolismo. Finalmente, tras varios estudios complementarios, por medio de un exoma trío se arribó al diagnóstico de síndrome de microduplicación del cromosoma 7q11.23, lo que justifica tanto el retraso global de desarrollo del paciente como su clínica neurológica. (AU)
A six-year-old boy presents with a history of language delay that led his parents to make multiple consultations. At first, we interpreted his condition as part of a global developmental delay. Subsequently, the patient presented seizures and episodes of metabolic decompensation, and since then, he had to be followed up by neurology, genetics, and metabolism services. Finally, after several complementary studies, following a trio exome analysis, we diagnosed chromosome 7q11.23 microduplication syndrome, which explains his global developmental delay and neurological symptoms. (AU)
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Humanos , Masculino , Niño , Cromosomas Humanos Par 7/genética , Discapacidades del Desarrollo/genética , Síndrome de Williams/genética , Duplicación Cromosómica , Trastornos del Desarrollo del Lenguaje/genética , Discapacidad Intelectual/genética , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/metabolismo , Pruebas Genéticas , Síndrome de Williams/diagnóstico , Síndrome de Williams/metabolismo , Trastornos del Desarrollo del Lenguaje/diagnóstico , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/metabolismoRESUMEN
Peroxisome biogenesis disorder are related to spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterized by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. We report a case of Zellweger syndrome, confirmed by clinical, biochemical and molecular findings, diagnosed in context of dysmorphism, and seizures.
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Objective:To explore the characteristics of blood amino acid and acylcarnitine profiles in children with unexplained generalized developmental delay (GDD)/intellectual disability (ID), and provide useful exploration for their early clinical identification.Methods:A total of 1 087 children with unexplained GDD/ID and 100 children with normal development who visited the Department of Pediatrics at Xiangya Hospital, Central South University from October 2015 to January 2021 were included as the study subjects. High performance liquid chromatography tandem mass spectrometry was used to detect 107 amino acids, carnitine, and base carnitine in dry blood filter paper. Unsupervised principal component analysis (PCA) was used to observe differences in metabolic profiles among different groups. Orthogonal partial least squares discriminant analysis (OLPS-DA) was used to distinguish inter group differences between different groups. Candidate differential metabolites were screened using VIP>1.0 and P<0.05 as criteria. Results:The GDD group screened 28 differential metabolites of blood amino acids and acylcarnitine, while the ID group screened 27 differential metabolites of blood amino acids and acylcarnitine, mainly involving pathways such as arginine biosynthesis, histone metabolism, arginine and proline metabolism.Conclusions:Differential metabolites such as glutamine in whole blood are of great significance for early identification of GDD/ID.
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Objective:To observe the clinical efficacy of mouse nerve growth factor (mNGF) combined with rehabilitation on children with global developmental delay(GDD).Methods:It was a prospective multicenter clinical randomized controlled trial (RCT) involving 120 children with GDD admitted to 5 hospitals in China from May 2020 to January 2022.They were randomly divided into mNGF group and conventional rehabilitation group using block randomization method.All children were managed by standardized rehabilitation after recruitment, and those in the mNGF group were additionally given mNGF injections.All subjects were surveyed using the Gesell Development Diagnosis Schedules(GDDS) at baseline, 90 days and 120 days after treatment, and their developmental quotient (DQ) was recorded.Clinical efficacy was analyzed by the paired t-test, rank sum test and Chi- squared test. Results:After 90 days of treatment and the continuous follow-up to 120 days, the increases in the DQ of gross motor (7.520±13.900 vs.0.450±11.459), fine motor (7.800±15.346 vs.1.250±11.581), adaptive behavior (7.730±13.428 vs.2.100±12.022) and personal-social behavior (6.780±11.651 vs.1.780±10.120) than baseline were significantly higher in mNGF group than those of conventional rehabilitation group (all P<0.05). Serious adverse events and important drug-related medical events were not reported. Conclusions:mNGF combined with rehabilitation effectively enhances the development levels of gross motor, fine motor, adaptive behavior and personal-social behavior, and continuously improves the condition of GDD in children with a high safety.
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Objective:To investigate the characteristics of executive function of preschool children with high functioning autism spectrum disorder (HFA) and with global developmental delay (GDD), and the differences among HFA, GDD and typically developmental (TD) children.Methods:From January 2020 to January 2021, 20 male HFA, 20 male GDD and 20 male TD children aged 4-6 years who visited the Psychological Behavior Clinic of the Child Health Department of Guiyang Maternal and Child Health Hospital and the Developmental Behavior Clinic of the Children Health Department of the Ninth People's Hospital in Chongqing were selected for comparative study.The executive function of HFA, GDD and TD children was assessed with the behavior rating scale of executive function-preschool version(BRIEF-P) and the executive function task program (EF-TOUCH). SPSS 26.0 software was used for statistical analysis, including variance test, independent sample t-test, χ2 test, Kruskal Wallis test and Mann-Whitney U test. Results:In the EF-TOUCH program task, the accuracy of the three groups of children's performance in the pig task (Pig), the silly sounds game (SSG), the working memory task (pick the picture, PTP) and the task of cognitive flexibility (something's the same, STS) were statistically different(Pig: HFA group: 0.87(0.76, 0.99), GDD group: 0.97(0.85, 0.99), TD group: 1.00(0.98, 1.00), χ2=15.646, P<0.001; SSG: HFA group: 0.76(0.53, 0.91), GDD group: 0.76(0.65, 0.99), TD group: 0.94(0.76, 1.00), χ2=6.448, P=0.040; PTP: HFA group: 0.66±0.18, GDD group: 0.66±0.19, TD group: 0.78±0.11; F=3.221, P=0.048; STS: HFA group: 0.67(0.63, 0.70), GDD group: 0.72(0.46, 0.78), TD group: 0.87(0.83, 0.90), χ2=26.898, P<0.001). The accuracies of Pig, SSG, PTP and STS in HFA group were significantly lower than those in TD group(all P<0.05), and the accuracies of Pig and STS in GDD group were significantly lower than those in TD group(both P<0.05). In inhibition control, there were statistically differences in response time of Pig and SSG among the three groups (Pig: HFA group: (1 694.36±222.83)ms, GDD group: (1 513.46±244.91)ms, TD group: (1 444.84±197.95)ms, F=5.810, P=0.005; SSG: HFA group: (2 202.42±195.58)ms, GDD group: (2 116.52±323.27)ms, TD group: (1 937.17±252.74)ms, Z=4.610, P=0.014). There were no significant differences in the reaction time of Arrows task ( P>0.05). There were significant differences in BRIEF-P inhibition control, organizational planning, inhibition self-regulation, cognitive flexibility and total scores among the three groups ( P<0.05), while there were no significant differences in the scores of other factors and dimensions ( P>0.05). Conclusion:The executive function of pre-school children with high functioning autism spectrum disorder and children with global developmental delay is impaired.The executive function of children with high functioning autism spectrum disorder and children with global developmental delay is significantly different from that of typically developmental children of the same age.Moreover, the executive function of children with HFA is more severely damaged from all components than that of children with GDD.
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Objective:To analyze the clinical characteristics and genetic features of SMC1A gene related disorders. Methods:The data of 5 children with SMC1A gene variants were collected from Children′s Hospital of Fudan University from February 2018 to January 2022. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results:Among the 5 patients, 4 are females and 1 is male. Two female cases are siblings. One boy had dysmorphic features, consisting of bilateral ptosis, synophrys, a short nose and upturned nasal tip. He also had patent foramen ovale plus atrial septal defect, unilateral cryptorchidism and microcephaly. Three cases had microcephaly. Two girls had patent foramen ovale, and 2 girls had microcephaly. Four cases had epilepsy, and age at seizure onset ranged from 2 to 52 months. Multiple seizure types were observed, including bilateral tonic clonic seizures in 2 patients, and focal seizures in 3 patients. The seizures in 3 cases were in cluster. All patients had developmental delay, including 1 patient with mild and 4 patients with moderate to severe developmental delay. Three patients had slow background activity in EEG. Interictal EEG showed abnormal discharges in 4 patients, including focal discharges in 3 cases and generalized discharges in 1 case. Brain magnetic resonance imaging was normal in 3 patients and showed mild cortical thickening in 1 case. All cases harbored 4 SMC1A gene variants, including 2 missense variants and 2 frameshift variants (c.580_587del, c.2699delG, c.3362G>A, c.1486C>T). Three cases harbored heterozygous SMC1A variants and 2 cases carried somatic mosaic SMC1A variants with 17.5% and 88.1% mosaicism in peripheral blood. The follow-up lasted for 3 months to 4 years. The epilepsy was refractory in 2 cases. During the follow-up, all cases had very slow developmental progress or developmental retardation. All cases had different levels of growth retardation. The scores of Cornelia de Lange syndrome (CdLS) phenotypes in 5 cases were 2-6. One case had the combined phenotypes of atypical CdLS and developmental epileptic encephalopathy (DEE). The phenotype was atypical CdLS in 1 case and DEE in 1 case. The phenotypes of 2 cases with SMC1A missense variants were mild, manifesting as non-refractory epilepsy and moderate to severe developmental delay. Conclusions:All of cases with SMC1A gene variants have developmental delay. Most of the patients have clusters of seizures and some dysmorphisms. The phenotypes of SMC1A gene related disorders are diverse. Except CdLS and DEE, there are some patients with mild phenotype due to missense variants of SMC1A gene.
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Objective:To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency (ECHS1D) caused by enoyl-CoA hydratase short chain 1 ( ECHS1) gene mutation. Methods:The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed, and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results:The child was a 6 months and 4 days old male, with acute onset, the main clinical manifestation being limb movement disorder after admission. The child had slow motor development, his head was still upright and cannot turn over, the child also cannot sit alone, follow up and make a laugh, and the muscle tension of limbs was increased. The child′s blood lactate was increased to 6.2 mmol/L, which suggested metabolic acidosis, and magnetic resonance imaging (MRI) of the head showed abnormal signals in the basal ganglia on both sides, abnormal enhancement of the meninges of the left cerebral hemisphere. Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene, c.563C>T (p.A188V) and c.5C>T (p.A2V), respectively. The child′s father carried c.563C>T mutation, the mother carried c.5C>T mutation, all of which were missense mutations. Conclusions:ECHS1 gene mainly has missense mutations, most of which are compound heterozygous mutations, and a few are homozygous mutations. The ECHS1D caused by ECHS1 gene mutation often affects infants and young children. MRI suggests abnormal signals in the basal ganglia; for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI, genetic testing should be considered to confirm the diagnosis.
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ObjectiveTo discuss the diagnostic methods of global developmental delay caused by 10q24.3 heterozygous loss. MethodsA retrospective analysis was conducted on the clinical data of one child with global developmental delay, and the results of low depth whole-genome copy number variation sequencing (CNVseq) and family whole exome sequencing (WES) of the child and his parents. ResultsThe patient was a 10-month-old male with developmental retardation in four areas, with some special features (ocular hypertelorism, strabismus, flat nose bridge, protruding forehead, cleft palate, high palatal arch, etc.) and hypotonia of limbs. The CNVseq and WES test showed that the patient had new 10q24.3 heterozygosis loss. Because this region contains the gene SUFU associated with basal cell nevus syndrome and the gene CNNM2 associated with hypomagnesemia, seizures, and mental retardation, and the gene TRIM8 associated of Focal segmental glomerulosclerosis with neurodevelopmental syndrome, we speculated that the cause of the disease in the child was highly related to the heterozygosity deletion of SUFU gene and CNNM2 gene and TRIM8 gene. ConclusionGenetic testing should be improved as soon as possible for children with global developmental delay and special facial manifestations, so as to make clear diagnosis and to judge prognosis.
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Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.
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Humanos , Masculino , Femenino , Niño , Lactante , Discapacidad Intelectual/genética , Discapacidad Intelectual Ligada al Cromosoma X/patología , Obesidad/complicaciones , Hipogonadismo/patologíaRESUMEN
ObjectiveTo describe the neuropsychological development screening of 0‒2 years in Tongzhou from 2017 to 2021 so as to understand the status and trend of developmental delay (DD). MethodsAnnual report data of 21 community health service centers in Tongzhou District from 2017 to 2021 were clustered, Chi square test was used to analyze the differences in positive rate and DD rate of children aged 0‒2 years with different ages and household registration, and Chi square trend test was used to analyze the linear trend of each age group and household registration. The Gesell test results in 762 children with developmental delay were analyzed, and Chi square test was used to compare the age distribution differences in gross motor, fine motor, language and personal-social behaviors. ResultsThe DD rate of children aged 0‒2 years in 2017‒2021 was 0.43%. A decreasing trend of DD rate in the 0‒ age group was observed (χ2=14.135, P<0.001), while an increasing trend of DD rate in the 1‒ and <3 age groups was observed (χ2=5.375, P=0.020; χ2=5.558, P=0.018). The DD rate of children aged 0‒2 years with Beijing household registration was higher (χ2=12.504, P<0.001). The DD rate of gross motor was the highest in the 0‒ age group (64.60%), the DD rate of language was the highest in the <3 age group (85.97%), and a statistically significant difference of gross motor and language was separately found in the three age groups (χ2=183.061, P<0.001; χ2=78.450, P<0.001). ConclusionAge and Beijing household registration are the influencing factors of DD for children aged 0‒2, and 0‒ years and <3 years are the critical periods for guidance and intervention to promote the development of gross motor and language abilities.
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OBJECTIVES@#To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD).@*METHODS@#A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier.@*RESULTS@#DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%.@*CONCLUSIONS@#Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.
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Niño , Humanos , Trastorno del Espectro Autista/psicología , Diagnóstico Diferencial , Aprendizaje Automático , Conducta SocialRESUMEN
Resumen Introducción: El síndrome por deficiencia de CDKL5 es originado por variantes patogénicas en el gen CDKL5, con un espectro clínico variable que va desde pacientes con características del trastorno del espectro autista hasta epilepsia de inicio temprano y refractaria al tratamiento. Inicialmente fue considerado como una forma atípica de síndrome de Rett. Casos clínicos: Presentamos tres pacientes no relacionadas, evaluadas por retraso global del desarrollo y epilepsia refractaria. Los tres casos eran hemicigotos a una variante patógena de CDKL5. En una paciente se realizó panel de 306 genes asociados con epilepsia; en las otras dos se realizó microarreglo genómico comparativo. Las características clínicas y los hallazgos en el electroencefalograma y la resonancia magnética cerebral se han descrito clásicamente en el espectro de manifestaciones de este síndrome. Conclusiones: El síndrome por deficiencia de CDKL5 representa un reto para los médicos, ya que en muchos casos las manifestaciones clínicas y los estudios electroencefalográficos y de neuroimagen pueden ser inespecíficos. Debe sospecharse este síndrome ante la presencia de retraso global del desarrollo, fenotipo conductual autista y epilepsia, asociado o no con dismorfias. Dada la similitud entre diversas encefalopatías epilépticas, se deben solicitar paneles multigénicos que incluyan la secuenciación y el análisis de duplicación/deleción en los que se contemple este gen y sus posibles diagnósticos diferenciales, aunque sin olvidar la utilidad de las técnicas genómicas en casos poco claros.
Abstract Background: CDKL5 deficiency syndrome is caused by pathogenic variants in the CDKL5 gene, with a variable clinical spectrum ranging from patients with characteristics of autism spectrum disorder to early-onset epilepsy refractory to treatment. Initially, until the gene was discovered, it was considered an atypical form of Rett syndrome. This study aimed to describe the clinical and molecular heterogeneity in CDLK5 disorders among three female patients with CDKL5 pathogenic variants. Case reports: We reported three unrelated Mexican female patients evaluated for global developmental delay and epilepsy. All three cases were hemizygotes to a CDKL5 pathogenic variant. In one patient, we performed a 306 gene panel associated with epilepsy. In the other two cases, a human genomic microarray was performed. We describe their clinical features electroencephalogram and brain magnetic resonance evaluations. Conclusions: CDKL5 deficiency syndrome represents a challenge for clinicians since the clinical manifestations, electroencephalographic and neuroimaging studies can be non-specific. This syndrome should be suspected in the presence of global developmental delay, autistic behavioral phenotype and epilepsy, associated or not with dysmorphia. Given the similarity between various epileptic encephalopathies, multigene panels including sequencing and duplication/deletion analysis should be requested in which this gene and its possible differential diagnoses are considered, without forgetting the usefulness of genomic techniques in unclear cases.
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Abstract We aimed to characterize the clinical spectrum of patients diagnosed with SRD5A3-CDG, a subtype of congenital disorders of glycosylation (CDG) due to variants in the steroid 5a-reductase type 3 (SRD5A3) gene. It presents with multi-systemic involvement including neurological disability, dermatologic abnormalities, and ophthalmological defects. We conducted a cross-sectional study of children (n=6, ages 4-16 years) with a confirmed diagnosis of SRD5A3-CDG (c.57G>A, p.W19X). Families completed a detailed medical history questionnaire, two quality of life measures, and an adaptive behavior scale. Prevalent clinical features in our cohort included visual impairment (6/6), developmental delay (6/6), nystagmus (5/6), retinal dystrophy (4/6), and hypotonia (3/6). The Vineland Adaptive Behavior Scales demonstrated deficits across all functional domains (Composite Mean 36.17 ± 26.88), although one child did not show significant deficits. The QI-Disability Form demonstrated a mean total score of 64.8 (±12.7), and the PedsQL-Family Impact Module demonstrated a mean total score of 56.5 (±31.5). Vineland composite scores did not correlate with levels of disability captured by the QI-Disability Form (Pearson Correlation range -0.63 to +0.69, p>0.05 on all subscales). Ultimately, despite genotypic homogeneity, there is notable variability in adaptive functioning and quality of life among affected children that does not correlate with age.
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Background: A neurological assessment before discharge from the NICU would enable early targeted intervention to mitigate the risk and severity of cerebral palsy (CP) and neurodevelopmental disability. Objective: To assess the accuracy of general movements (GM) in the preterm and fidgety movement periods in predicting neurodevelopmental disability and cerebral palsy in very preterm infants (?32 weeks gestational age) at 18-24 months corrected gestational age. Study design: Prospective cohort study Participants: One hundred and seventy very preterm infants, mean (SD) gestation 29.8 (1.32) weeks, and birthweight 1215 (226) g. Outcomes: Infants underwent GM assessments in the preterm period (31-36 weeks post-conception age) and fidgety movement period (8-18 weeks post term age). Neurodevelopmental outcomes were assessed in 127 children using the Griffiths Mental Developmental Scales-2. Results: Nine children had neurodevelopmental disability (two infants with cerebral palsy and seven with global developmental delay. The relative risk (95% CI) for neurodevelopmental disability was 1.46 (0.31-6.89) with preterm movements and 6.07 (0.97 – 38.05) with fidgety movements. Sensitivity and specificity values for the prediction of neurodevelopmental disability were 33% and 64% in the preterm period and 25% and 92% in the fidgety movement period, respectively. The sensitivity and specificity values for prediction of CP were 50% and 63% in the preterm period and 100% and 93% in the fidgety movement period, respectively. Conclusion: Preterm movements showed lower sensitivity and specificity than fidgety movements in predicting later CP and neurodevelopmental disability in preterm infants.
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Resumen Los trastornos del neurodesarrollo (TND) constituyen un grupo relevante de enfermedades, con base biológica y etiología total o parcialmente genética. El reconocimiento de los factores causales cons tituye un reto cuyos resultados se han perfeccionado a lo largo de las últimas décadas, hasta obtener un rédito diagnóstico cada vez mayor. La implementación de estos avances tecnológicos solo puede lograrse mediante la conformación de equipos de trabajo interdisciplinarios, que siguiendo un proceso ordenado, logran un diag nóstico de presunción, que luego es certificado mediante las técnicas que, para cada uno de los casos, resulta más redituable en calidad y costo. En este trabajo, enumeramos estos procedimientos a partir de diferentes escenarios que ponen de relieve el extenso menú de posibilidades y la necesidad de administrar los mismos de un modo racional, sobre bases científicas debidamente fundadas.
Abstract Neurodevelopmental disorders (NDD) constitute a relevant group of pathologies, of childhood, with a biological basis and totally or partially genetic etiology. The recognition of the causal factors constitutes a challenge that has been perfected over the last decades, until obtaining an increasing diagnostic yield. The implementation of these technological advances can only be achieved through the formation of interdisciplinary work teams, which, following an or derly process, achieve a presumptive diagnosis, which is then certified using the techniques that for each of the cases are more profitable in terms of quality and cost. In this paper we list these procedures, based on different scenarios that highlight the extensive menu of possibilities and the need to manage them in a rational way, on well-founded scientific bases.
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Objective: To validate the Hindi translation of Survey of well-being of young children (SWYC), a screening questionnaire to detect developmental delay and emotional-behavior problems by primary caregivers in Indian children. Methods: This cross-sectional observational study was done at the child development clinic of our private-sector tertiary care hospital. 180 children of either sex, 60 each in age group of 9, 18 and 24 months were enrolled in the study (30 high-risk and 30 low-risk in each group). Hindi translated version of SWYC age-specific questionnaire was administered to the parents, followed by a standardized development assessment by using the Bayley Scale of Infant and Toddler Development (BSID III). Results: SWYC Milestone score and Emotional/behavior scores showed a statistically significant correlation with BSID III (P<0.001). Milestone score’s overall sensitivity in detecting developmental delay was 94.4% and specificity was 93.4%. The sensitivity was best for the 24-month (100%) and specificity was best for 18-month questionnaire (96.7%). Behavioral score’s overall sensitivity was 68.4% and specificity 92.3%. The best sensitivity was for 18-month questionnaire (72%), and specificity for 24- month questionnaire (100%). SWYC had better sensitivity for detecting developmental delay in high-risk group (95.4%), and higher specificity in low risk group (95.5%). Conclusion: SWYC has strong test characteristics for detecting milestone delay and emotional/behavior problems in Indian children.
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Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an extremely rare autosomal dominant disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, hearing loss, and optic nerve atrophy. This syndrome is caused by loss-of-function variants in the nuclear receptor subfamily 2 group F member 1 ( NR2F1 ) gene. To date, approximately 80 patients have been reported with BBSOAS. Here, we describe a 3-year-old infant with delayed development, intellectual disability, strabismus, nystagmus, and optic atrophy with well-characterized features associated with BBSOAS. Whole-exome sequencing revealed a novel heterozygous missense mutation (NM_005654.6:c.437G>A, p.Cys146Tyr) in the NR2F1 gene. This missense variant is predicted to be deleterious by the protein prediction tools (SIFT, PolyPhen-2, and MutationTaster). To the best of our knowledge, this is the first patient with BBSOAS reported from Turkey.