Speech Delay Research Articles

The clinical and genetic spectrum of paediatric speech and language disorders.

Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization of speech and language disorders in 52 143 individuals, reconstructing clinical histories using a large-scale data-mining approach of the electronic medical records from an entire large paediatric healthcare network. The reported frequency of these disorders was the highest between 2 and 5 years old and spanned a spectrum of 26 broad speech and language diagnoses. We used natural language processing to assess the degree to which clinical diagnoses in full-text notes were reflected in ICD-10 diagnosis codes. We found that aphasia and speech apraxia could be retrieved easily through ICD-10 diagnosis codes, whereas stuttering as a speech phenotype was coded in only 12% of individuals through appropriate ICD-10 codes. We found significant comorbidity of speech and language disorders in neurodevelopmental conditions (30.31%) and, to a lesser degree, with epilepsies (6.07%) and movement disorders (2.05%). The most common genetic disorders retrievable in our analysis of electronic medical records were STXBP1 (n = 21), PTEN (n = 20) and CACNA1A (n = 18). When assessing associations of genetic diagnoses with specific linguistic phenotypes, we observed associations of STXBP1 and aphasia (P = 8.57 × 10-7, 95% confidence interval = 18.62-130.39) and MYO7A with speech and language development delay attributable to hearing loss (P = 1.24 × 10-5, 95% confidence interval = 17.46-infinity). Finally, in a sub-cohort of 726 individuals with whole-exome sequencing data, we identified an enrichment of rare variants in neuronal receptor pathways, in addition to associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9 and UMODL1 with aphasia. In summary, our study outlines the landscape of paediatric speech and language disorders, confirming the phenotypic complexity of linguistic traits and novel genotype-phenotype associations. Subgroups of paediatric speech and language disorders differ significantly with respect to the composition of monogenic aetiologies.

INTERVENSI DINI BAHASA DAN BICARA ANAK SPEECH DELAY

Language development is one indicator of the overall development of the achievement of cognitive abilities of children Language and speech delays must be recognized by parents from an early age, so that the management provided can maximize the language and speech capacity of children. This research was conducted to describe strategies for implementing early language and speech interventions. talk to children with speech delay The research method used is a qualitative approach with a case study design. This research was conducted at the Happy Living Tesbatan Amarasi PAUD with a total of five children aged 4 years. Data collection techniques through observation, interviews and documents (diaries, checklist documents instrument for assessing achievement of language and speech development, video of early intervention program activities) Method of data analysis using descriptive analysis with a qualitative approach Based on the results of the discussion it can be concluded that there is an increase in language and speech of children with speech delay after being given early intervention Improved language and speech skills can be proven from the results checklist instrument by marking the achievement of language and speech indicators, namely children are able to answer simple questions, express feelings with adjectives, express wishes and mention familiar words

Chromosome 15q11-q13 Duplication Syndrome: A Review of the Literature and 14 New Cases.

The 15q11.2q13 chromosomal region is particularly susceptible to chromosomal rearrangements due to low-copy repeats (LCRs) located inside this area. Specific breakpoints (BP1-BP5) that lead to deletions and duplications of variable size have been identified. Additionally, this specific region contains several imprinted genes, giving rise to complex syndromes (Prader-Willi, Angelman and 15q11-q13 duplication syndromes). 15q11.2-q13 duplication syndrome has been associated with neurodevelopmental disorders (hypotonia, developmental delay, speech delay and seizures) and ASD but is characterized by variable expressivity and reduced penetrance, features that make genetic counseling a complex procedure especially in prenatal cases. In the present study, a total of 14 pre- and postnatal cases were diagnosed as 15q11.2q13 duplication carriers using Affymetrix CytoScan 750 K array-CGH, and our analysis combined these with 120 cases existing in the literature. The inheritance pattern of the cases of this study is unknown, but as a review of the literature revealed, 62.96% of the affected carriers inherited the duplicated area from their mother. The combined results of this analysis (the present study and the literature) show that in the majority of the cases, the phenotype is a compound phenotype, with clinical characteristics that include ASD, intellectual disability, developmental delay and an absence of speech. The aim of this paper is to deliver new possibilities to genetic counseling that can be provided in prenatal and postnatal cases as the phenotype of 15q11.2q13 microduplication carriers cannot be fully predicted; so, clinical diagnoses should be a combination of molecular findings and clinical manifestations that are present.

7238 A rare cause of primary ovarian failure in an adolescent due to a genetic mutation in mitochondrial poly-A-polymerase (mTPAP) mRNA

Abstract Disclosure: J. Epstein: None. S. Veera: None. J. Pappas: None. B.C. Shah: None. Primary ovarian insufficiency (POI) is a dysfunction or loss of ovarian follicles with associated amenorrhea. While most causes are idiopathic, approximately 15% of POI cases are due to single gene or chromosomal abnormalities, such as X chromosome abnormalities. Many of these nuclear genes encode for proteins that function within the mitochondria. Mitochondrial disorders affect tissues with high energy demand, such as the neurological, skeletal, cardiac, and endocrine systems. Furthermore, mature ovaries have a relatively higher concentration of mitochondria, which play a role in cellular respiration along with steroidogenesis. Mutations that disrupt these pathways can therefore lead to ovarian dysfunction. We present a case of a 17-year-old female with concern for primary amenorrhea. She underwent pubarche at age 12 years and thelarche at 14 years, with slowed progression. Height Z score was -1.61 and weight Z score was -0.41. Lab work at presentation was significant for LH 18.6 IU/L (N 2.4-12.6 IU/L), FSH 43.9 IU/L (N 1.1-9.6 IU/L), low estradiol <2.5 pg/mL (N 30-100 pg/mL), low total testosterone 8.3 ng/dL (N 15-31 ng/dL), unremarkable HbA1C, cortisol, thyroid levels, and a 46 XX karyotype. Pelvic ultrasound showed small ovarian volumes with a 1.9 cc right ovary, 1.5 cc left ovary consistent with lack of hormonal stimulation, and uterus length of 4.9 cm (N > 4 cm) consistent with early hormonal stimulation. She was started on transdermal estrogen replacement. Past medical history included stable pericardial effusion, episodes of supraventricular tachycardia, pre-cataracts, speech delays, mild learning disabilities, spastic diplegia, progressive gait abnormalities, ligamentous laxity, and recurrent patellar dislocations requiring multiple orthopedic limb surgeries. Family history was significant for parental consanguinity as first cousins. As the etiology of the POI remained unknown, genetic testing was completed. Whole exome sequencing (WES) revealed a homozygous pathogenic variant in the MTPAP gene: p.(Leu495Arg) (CTG>CGG): c.1484 T>G in exon 9 on chromosome 10p11.23. MTPAP, also known as SPAX4, TENT6, or PAPD1, is a nuclear-encoded polymerase involved in synthesizing the 3’ poly(A) tail of mitochondrial transcripts as well as in mRNA degradation. She was diagnosed with autosomal recessive MTPAP-related neurodevelopmental and movement disorder. Monogenic disorders affecting mitochondrial function are rare causes of POI. A high index of suspicion should be raised when a constellation of neurological, musculoskeletal, and cardiac problems co-exist. WES can be a very useful tool for uncovering rare genetic disorders. Further studies are needed to clarify details of organ specific mitochondrial dysfunction and possible therapeutics in individuals affected with MTPAP-related neurodevelopmental and movement disorders. Presentation: 6/1/2024

8428 Rare Variants in the MECP2 Gene in Two Boys with Central Precocious Puberty

Abstract Disclosure: A.P. Canton: None. J.B. Mebarak: None. M. Magnuson: None. S. Roberts: None. N. Mauras: None. M. Benson: None. S. Witchel: None. R.S. Carroll: None. A. Latronico: None. U.B. Kaiser: None. A. Abreu: None. Introduction: Central precocious puberty (CPP) occurs more frequently in girls and is usually labelled as idiopathic; however, in boys organic causes are more frequent. Identification of imprinted genes causing CPP have revealed epigenetic mechanisms underlying puberty. MECP2, an X-linked gene, encodes a methylated DNA reader protein with a role in gene transcription. MECP2 loss-of-function mutations usually cause Rett syndrome, a severe neurodevelopmental disorder that may be associated with early pubertal development. Recently, rare variants in MECP2 have been recognized in girls with sporadic CPP with or without mild neurodevelopmental disorders. In our cohort of 78 patients with idiopathic CPP, no MECP2 mutations were identified in 73 girls. In this study, five boys with CPP were evaluated for potential MECP2 sequence variants. Methods and Results: Five boys with CPP were screened for MECP2 sequence variants using Sanger sequencing. At the time of CPP diagnosis, they had median (interquartile range) chronological age 9.2 yr (4.3), bone age advancement 2.1 yr (3.5), height SDS 2.3 (1.5), basal LH levels 1.6 IU/L (0.9), and testosterone levels 370 ng/dL (570). Organic causes of CPP were excluded. No MKRN3 or DLK1 mutations were identified. Familial segregation analysis was performed when appropriate. We identified a hemizygous MECP2 variant in a boy (Patient 1) who presented at age 2.7 yr with sporadic CPP. In addition, he had speech delay and behavioral changes, defined as autism spectrum disorder by neuropsychological assessment. He harbored an extremely rare (gnomAD AF=0.000004956) missense variant (p.Val312Ile) in exon 3 of MECP2, encoding the transcriptional repression domain, critical for protein function. The p.Val312Ile mutation was classified as likely pathogenic (ACMG criteria) with a potential association with the phenotype. Another hemizygous MECP2 variant was identified in a boy (Patient 2) who presented at age 8.0 yr with sporadic CPP; he had no neurodevelopmental conditions. He harbored a rare (gnomAD AF=0.00008) missense variant (p.Arg366Cys) in exon 3, encoding the C-terminal domain, classified as a variant of uncertain significance (ACMG criteria). Familial segregation analysis revealed that both boys inherited the MECP2 variants from their unaffected mothers, consistent with a pattern of clinical variability described in women with defects in X-linked genes.Conclusions: We identified rare MECP2 variants in two boys with sporadic CPP without classic features of Rett syndrome, expanding the phenotype of patients with MECP2 mutations, as described in girls. The MECP2 p.Val312Ile variant was likely pathogenic, whereas the functional significance of the p.Arg366Cys variant in still indeterminate. These findings provide additional evidence for a role of MECP2, an epigenetic factor, in the hypothalamic control of pubertal timing. Presentation: 6/1/2024

7341 Establishing a Multidisciplinary Care Program for patients with Klinefelter Syndrome and other Aneuploidy X and Y Variations

Abstract Disclosure: C.J. Romero: None. N.R. Malhotra: None. A. Norris-Brilliant: None. C. Mintz: None. Objectives: Klinefelter syndrome (KS) is one of the most common genetic aneuploidies denoted by a XXY karyotype and affects up to 1 in 600 patients. Most patients are not diagnosed until adolescent years or adulthood. KS is one of the leading causes of male infertility and testosterone insufficiency. KS is also associated with developmental delays, particularly speech and language delay. Advances in genetics screenings has led to early identification of KS and other aneuploidy X and Y variations, access to neurodevelopmental screening and fertility preservation resources during adolescence and young adulthood. We believe a multidisciplinary program for KS can provide the necessary resources for patients and families at any age from infancy to young adulthood. Methods: A group of faculty from the divisions of pediatric endocrinology, genetics, urology and psychiatry assembled in 2023 to establish a multidisciplinary clinic (MDC) to provide comprehensive care to patients/parents; this ranged from prenatal diagnosis to young adulthood. Two major challenges of care are access to neuro-psychological evaluations and fertility preservation options. Testosterone supplementation requires appropriate referral to endocrinology and timing of treatment remains controversial. Our goals include: expertise guidance and planning after prenatal diagnosis or later in age; access to cost effective neuro-psychological testing during early childhood years; urological consultation beginning in early puberty to educate and prepare patients for choices of surgical and non-surgical options of fertility preservation. Results: Our current center cares for 12 patents ranging from ages 3 months to 21 years. Of this cohort, 3 (25%) of the patients had initial consultations with the parents during pregnancy. 7 (58%) of the patients were of pubertal age that one would consider testosterone replacement, but only 3 (43%) were taking testosterone. Only 1 patient of school age reported neuro-psychological evaluation that was completed at a different institution. No patients received testosterone supplementation during year one of life. Conclusions: A multidisciplinary team can offer simultaneous assessment, anticipatory guidance and management for KS patients and their families. It is a comprehensive resource to our community. Prenatal genetic screenings bring awareness to this diagnosis and therefore timely education toward understanding the lifelong management of KS. Identifying developmental delays early in childhood will help with scholastic success. Monitoring of pubertal development will ensure appropriate pubertal progression in addition to education and management of fertility preservation. Undoubtedly future urological advances will assist patients more effectively. We believe our model provides the access to resources that allow our patients and family to successfully thrive. Presentation: 6/2/2024

Fetal MRI findings, etiology, and outcome in prenatally diagnosed schizencephaly.

Schizencephaly is a rare brain anomaly which is increasingly detected in utero. There are limited data on the etiology and outcomes in fetal schizencephaly to guide workup and counselling. We aim to determine the associated imaging findings, etiology, and outcomes in schizencephaly detected in utero. This retrospective cohort study included 22 fetuses with a total of 34 schizencephaly defects identified by keyword search of fetal MRI reports from 1996-2022 followed by image review. Follow-up fetal and postnatal imaging, when available, were reviewed. Data on demographics, etiology, and outcomes were extracted from the electronic medical record. The schizencephaly defect was open in 28/34, most common in the MCA territory (23/34), and commonly involved the frontal (16/34) lobe. Additional intracranial abnormalities were seen in all fetuses including other cortical malformations (CM, 13/22), abnormal posterior fossa (12/22), abnormal corpus callosum (10/20), and intraparenchymal hemorrhage (9/22).The cause of schizencephaly was classified as secondary (as evidenced by intraparenchymal hemorrhage at schizencephaly, monochorionic twin gestation, infection, or maternal/placental risk factor) in 64% (14/22), potentially genetic in 9% (2/22), and unknown in 27% (6/22). Among those liveborn (n=8), the following outcomes were observed: postnatal death (1/8), tube feeding (1/7), shunted hydrocephalus (1/7), epilepsy (4/7). Among those >1 year of age, cerebral palsy (4/5) and speech delay or intellectual disability (3/5) were common. CM remote from schizencephaly was associated with epilepsy (p=0.03). On postnatal imaging, open defects often involuted (8/11) and there were high rates of new/additional findings (4/6). In this cohort, fetal schizencephaly was always associated with additional intracranial abnormalities. In most cases, there was evidence that schizencephaly was likely secondary to prior injury. Imaging characteristics may provide clues regarding neurodevelopmental outcome. Postnatal imaging is crucial in assessing evolution as well as for detection of additional abnormalities. ICH = intracranial hemorrhage; CM = cortical malformation; VM = ventriculomegaly; DGN = deep grey nuclei; SP = septum pellucidum; IPH = intraparenchymal hemorrhage; CC = corpus callosum; PMG = polymicrogyria; PVNH = periventricular nodular heterotopia; TTTS = twin-twin transfusion syndrome; GA = gestational age; CP = cerebral palsy.

A-310 Neurodevelopmental disorders and hyperlipidemia in HIV-exposed uninfected children in the Bronx, New York

Abstract Background The implementation of combination antiretroviral therapy (cART) for treating human immunodeficiency virus (HIV) has significantly reduced the rates of vertical HIV transmission. With increasing cART coverage, the number of HIV-positive infants has declined, while the number of HIV-exposed uninfected (HEU) infants has risen. This group now comprises a rapidly expanding cohort of HIV-affected individuals, currently totaling 16 million and increasing by 1.6 million annually. However, our understanding of the potential in-utero toxicity of cART remains limited. Numerous studies, primarily from Africa, suggest that HEU children may face heightened risks of adverse health outcomes, including growth restriction, increased susceptibility to infections, and neurobehavioral disorders. It is widely recognized that infants with growth restriction are at a greater risk of developing chronic diseases such as cardiometabolic and neurological disorders later in life, which is accentuated by low socioeconomic status. The objective of this study was to assess the prevalence of neurodevelopmental disorders and hyperlipidemia in HIV-negative children born to HIV-infected mothers in the Bronx, New York, utilizing retrospective medical records information. Methods We conducted a retrospective chart review of HEU and age-matched control (HIV-unexposed and uninfected; HUU) children (age 0-15 years) using clinical data obtained from the electronic medical record (EMR) at the Montefiore Medical Center in the Bronx, New York, between 2015 and 2023. Demographic data and documented diagnostic data were collected. Lipid panel results were also obtained from the EMR and stratified by age and testing date. Neurodevelopmental outcome measures were compared between HEU and HUU children using Chi-square and Student’s t-test was used for continuous variables. Results A total of 127 HEU (46% females, 54% males) children and 157 HUU (46% females, 54% males) children were analyzed. Among the HEU children, 12 (9.5%) were diagnosed with attention-deficit/hyperactivity disorder (ADHD), while only 1 out of 157 (0.6%) HUU children had this diagnosis (p=0.0004). Similarly, a significant number of HEU children were found to have autism spectrum disorder, with 11 (8.7%) affected compared to 2 (1.3%) in the control group (p=0.0036). HEU children also exhibited a higher prevalence of unspecified developmental delay compared to HUU children (14.2% vs 5.1%; p=0.012). However, no significant differences were observed between the two groups regarding speech and language delay or learning difficulties. Abnormal cholesterol levels were detected in 33% of HEU children, while 54.5% had abnormal triglyceride levels. These percentages surpass the prevalence of pediatric hypercholesterolemia (7%) and hypertriglyceridemia (10.2%) in the United States. Conclusions Our findings indicate that HEU children born in areas designated as medically underserved and socioeconomically disadvantaged, such as the Bronx in the United States, face significant risks of neurodevelopmental disorders and hyperlipidemia. Considering the increasing population of HEU children, even minor rises in adverse health effects could lead to significant public health challenges. To support HEU children in achieving their utmost potential, further studies must be encouraged to understand these children's needs. Moreover, it is imperative to enact policies that facilitate equitable distribution of resources, ensuring timely screening and intervention in underprivileged communities.

Comparing Parent Perception of Neurodevelopment after Primary versus Staged Repair of Neonatal Symptomatic Tetralogy of Fallot

To assess the association between primary (PR) and staged repair (SR) of neonatal symptomatic tetralogy of Fallot (sTOF) and neurodevelopmental outcomes in preschool through school-age children. Multi-center cohort (n=9 sites) study of sTOF patients who underwent neonatal intervention between 2005 and 2017. The neurodevelopmental outcomes measures included caregivers' ratings of executive function with the Behavior Rating Inventory of Executive Function (BRIEF), and psychosocial functioning with the Behavior Assessment System for Children - 3rd Edition (BASC-3). Results were compared with normative data and by treatment strategy (PR versus SR). A parent survey assessed history of disabilities and access to services related to neurodevelopment. Although the majority of patients (median age 8.3 years, interquartile range 5.7-11.2) had median BRIEF and BASC-3 scores within the normal range, a proportion had clinically elevated (abnormal) scores, especially in the school-age patient subgroup (BRIEF 24-30% and BASC 20-37%). There were no statistically significant differences based on treatment strategy for either the BRIEF or BASC-3. However, lower birth weight, genetic syndrome, and medical complexity were significantly associated with worse executive function, and lower maternal education was associated in school age children with lower executive and psychosocial functioning. Ongoing disabilities were relatively common (learning disability 35%, speech delay 33%, developmental delay 31%), although up to 50% of children were not receiving educational or developmental services. Elevated executive and psychosocial concerns are present in the sTOF patient population. Although initial treatment strategy appears unrelated to neurodevelopmental outcomes, lower birth weight, genetic syndrome, and medical complexity, and lower maternal education are risk factors. Early recognition of neurodevelopmental concerns can facilitate access to appropriate neuro-developmental services in this high-risk group.

Treatment of Spastic quadriplegia resulting from hypoxia in newborn through body engineering technique-hand therapy Case Report Described by Parents: Qualitative study

Objectives: Summary of Case Report on Spastic quadriplegia accompanied by several disabilities. Treatment with Body Engineering/Hand Therapy. This case report describes the successful treatment of a 4 years old girl who was diagnosed with Spastic quadriplegia and global developmental delay accompanied with relapse, slurred speech, and cognitive delay resulting from hypoxia during child birth. To report a case of a girl who suffered Spastic quadriplegia, seizures, and delay in speech and perception due to hypoxia and to highlights the critical role of body engineering techniques for the rehabilitation of children with similar cases. Methods: An informed case report was given by from the child's parents. Functional recovery was achieved through a customized rehabilitation plan according to the body engineering / hand therapy techniques We highlight: -Medical Management for such cases. -A rehabilitation plan based on body engineering/ hand therapy techniques that led to complete recovery. -Satisfaction of the patient's parents after treatment. Results: Treating the patient through body engineering (hand therapy) and rehabilitating him for a full year led to the appearance of signs of clinical and radiographic improvement. Conclusions: Hypoxia-induced spastic quadriplegia often results in multiple disabilities, as seen in this case. Early intervention using body engineering techniques can lead to significant improvements in physical and cognitive functions. Continuous monitoring and rehabilitation are recommended to sustain progress and prevent relapses (Odding et al., 2006). Based on the provided information, body engineering and hand therapy have proven to be highly effective in rehabilitating a girl with hypoxia-induced cerebral palsy. Through a comprehensive rehabilitation program, the patient's physical, cognitive, and communication abilities have significantly improved. This case report underscores the importance of early intervention in maximizing outcomes for children with spastic quadriplegia. By providing ongoing support and tailoring rehabilitation programs to individual needs, it is possible to help these children reach their full potential, aligning with the World Health Organization's definition of rehabilitation as a process to improve performance and reduce disability.

The Analysis Study of Early Detection and Outcome of Speech Delay in Children: A Comprehensive Systematic Review

The Analysis Study of Early Detection and Outcome of Speech Delay in Children: A Comprehensive Systematic Review

Maternal Transmission of 17q12 Microdeletion: Intrafamilial Phenotypic Variability and Diagnostic Hurdles

The relatively rare proximal 17q12 microdeletion, including the deletion of the HNF1B gene, is associated with renal cysts and diabetes syndrome (RCAD). This genomic rearrangement results in a wide range of phenotypes, including renal cysts and diabetes, which are consistent with maturity-onset diabetes of the young type 5 (MODY5), Mullerian aplasia/dysgenesis, autism spectrum disorder and schizophrenia, speech delay, learning difficulties, transient neonatal hypercalcemia, and neonatal cholestasis. We describe a girl with a 17q12 microdeletion identified using CGH array analysis (about 1.4 Mb, including HNF1B and LHX1 genes). The same deletion was identified in her mother. The proband had shown cystic and hypodysplastic bilateral kidneys since birth and hypertension, while her mother had bilateral renal cysts and diabetes. Despite suggestive findings in the girl and in the mother, no clinical suspicion arose, and genetic testing was carried out only after referral to a pediatric nephrologist. In children, the identification of 17q12 microdeletion may have a significant impact on the diagnosis, prognosis, and management of renal disease and early-onset type II diabetes. This family with a 17q12 microdeletion confirms intrafamilial phenotypic variability and highlights the importance of including it early on in the analysis of the diagnostic workup of children with renal cystic diseases.

Early intervention speech-language pathologists’ beliefs and practices related to assessing dual language learners

IntroductionEarly intervention (EI) speech-language pathologists (SLPs) are required to provide culturally and linguistically responsive assessments for dual language learners (DLLs). However, SLPs consistently report feeling underprepared to assess DLLs and research demonstrates gaps in implementation of best practices in pediatric outpatient and school-based settings. This study was designed to understand EI SLPs’ beliefs and practices related to assessing DLLs referred to early intervention programs. MethodsA total of 132 EI SLPs completed a survey in which they were asked to describe their assessment procedures for a DLL case scenario and were further asked to identify the degree to which they agreed with a variety of assessment practices for assessing DLLs. ResultsResults revealed that EI SLPs’ beliefs aligned with best practices for assessing DLLs. However, substantial gaps exist between EI SLPs’ beliefs and their self-reported practices for assessing DLLs. ConclusionsThese results suggest DLLs may not be receiving evidence-based EI assessments, leading to the potential perpetuation of both over- and under-diagnosis of speech and language delays within this population. Implications include the need to increase the quality of EI SLPs assessment practices through additional training, the removal of systems-level barriers, and the continued need for increased training within preprofessional training programs.

Speech Delay and Excessive Gadget Usage: Understanding Pathophysiology Mechanism and Prevention Target Among Children Population

In this state of modern era, usage of electronic gadget has increased excessively with the last ten years. Usage of devices has increased especially among children and adolescent population as a form for information display, education, and entertainment. Problems that arise of electronic gadget usage among children and adolescent population is excessive usage, which defined as usage of gadget over two hours per day. The huge pitfall of this phenomenon is the increasing incident of developmental delay within children population, specifically speech delay. Speech delay development found to be high prevalent in children under five years old, and there are several studies that have discussed correlation between speech delay and excessive usage of gadget. These studies have found that speech delay that led by excessive usage of gadget could occur due to understimulation of certain brain regions that involved in words sensory and recognition, and speech motoric ability, especially during neurodevelopmental period. Understanding of pathophysiology mechanism between speech delay and excessive gadget usage is important for every healthcare provider to educate family and creating preventive strategies from individual, family, and community aspect.

Speech and Language Delay in Children: Child Neurology Experience

Speech and Language Delay in Children: Child Neurology Experience

Novel loss-of-function variants in WDR26 cause Skraban-Deardorff syndrome in two Chinese patients.

Mutations in the protein WD repeat structural domain 26 (WDR26, MIM 617424) have been identified as the cause of autosomal dominant Skraban-Deardorff syndrome, a rare genetic disorder characterized by intellectual disability (ID), developmental delay (DD), hypotonia, epilepsy, infant feeding difficulties, gait abnormalities and distinctive facial features. The objective of this study is to investigate the genetic factors that may contribute to the development of Skraban-Deardorff syndrome in affected individuals. In this study, we used whole-exome sequencing (WES) to analyze pathogenic and likely pathogenic variants in two unrelated Chinese patients with DD and ID. We confirmed the origin of the variants by conducting Sanger sequencing and classified them according to ACMG/AMP guidelines. Here, two novel de novo variants (c.1797delC(p.His599fs*11) and c.1414C>T(p.Gln472*)) in the WDR26 gene have been identified in two Chinese patients with Skraban-Deardorff syndrome. These patients exhibit a range of symptoms, including varying degrees of ID, DD, speech delay, an abnormal wide-foot and/or stiff-legged gait, facial dysmorphism, behavioural abnormalities, with or without seizures. In this study, We report two unrelated Chinese patients with Skraban-Deardorff syndrome caused by novel de novo pathogenic variants of the WDR26 gene. These patients showed a clinical phenotype similar to that of patients with the WDR26 variant. Compared to reported cases with WDR26 pathogenic variants, patient 2 presented a novel complication of severe behavioural problems, including hyperactivity, social anxiety, self-mutilation, impulsivity and violent behaviour. This research broadens the range of genetic and clinical features of Skraban-Deardorff syndrome. In addition, the symptoms may become more pronounced as the patient ages. Furthermore, our report highlights the clinical diversity of Skraban-Deardorff syndrome. The findings may assist healthcare professionals in providing more accurate genetic testing and counselling to affected families and improving the overall management of the condition.

Mucopolysaccharidosis Type I (Hurler – Scheie Syndrome): Case Report

Background. Mucopolysaccharidosis type I (MPS I) is an inherited disease caused by pathogenic variants in the IDUA gene, which encodes the lysosomal enzyme alpha-L-iduronidase. This clinical case demonstrates the importance of diagnosing rare diseases when patients have phenotypic features indicating hereditary pathology presence. Phenotype changes can be so-called “red flag” that helps specialists suspect and diagnose lysosomal storage diseases. Clinical case description. The patient was observed with delayed psychomotor development; she also had hepatomegaly and on auscultation of the heart there was a functional systolic murmur above the apex and in the Botkin–Erb point on heart auscultation. Coarse “garholoid” facial features attracted attention at external examination: large nose, wide sunken nose bridge, macroglossia, thick lips, synophrysis, scaphocephaly, wide chest, and flat-valgus feet. Echocardiography has revealed mitral valve insufficiency and hardened valve leaflets. Ophthalmologist examination: hypermetropic astigmatism. Psychiatrist examination: mental and speech development delay. Enzymatic diagnostics: significant decrease in alpha-Liduronidase activity. No further examinations were carried out due to the onset of the COVID-19 epidemic and parents' doubts about the diagnosis. The patient was readmitted to the hospital at the age of 6 years due to aggravation of her condition. A molecular genetic study has revealed two pathogenic variants in the IDUA gene. Diagnosis of MPS I was established according to the clinical data, results of biochemical and molecular genetic studies. Conclusion. This clinical case demonstrates the classic course of MPS I with typical phenotypic signs and lesions in various organs and systems. The presented case demonstrates the importance of professional vigilance among doctors of various specialties regarding orphan diseases.

Clinical features and genetic analysis of four children with Phelan-McDermid syndrome

To explore the clinical characteristics and genetic etiology of four children with Phelan-McDermid syndrome (PMS). Four children who had visited the Ningbo Women and Children's Hospital between June 2, 2022 and May 8, 2023 were selected as the study subjects. Clinical data of the children were collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and quantitative PCR (q-PCR) analysis. All children had presented with speech and language delays and intellectual disability. Children 3 and 4 also presented with autistic behaviors. WES showed that the children 1 and 2 had respectively carried a heterozygous c.731T>C (p.Leu244Pro) and a c.2782_2851del (p.Gly928ArgfsTer4) variant of the SHANK3 gene. Sanger sequencing confirmed that their parents did not carry the same variant, suggesting that they were de novo in origin. Children 3 and 4 had respectively harbored a 121 Kb and 52.02 Kb heterozygous deletion at chromosome 22q13.33, which had both encompassed the SHANK3 and ACR genes mapped to 22q13.33. q-PCR results showed that the deletion of SHANK3 and ACR genes were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.731T>C and c.2782_2851del variants were predicted to be likely pathogenic (PS2+PM2_Supporting+PP3) and pathogenic (PVS1+PM2_Supporting+PS2_Supporting), respectively. Furthermore, the 52.02 Kb and 121 Kb heterozygous deletions in 22q13.33 were both predicted to be pathogenic (2D+4C, 1.05 in score; 2D+4C, 1 in score). The four children were all diagnosed with PMS by genetic testing. Above finding has enriched the phenotypic and mutational spectrum of PMS, and provided a basis for clinical diagnosis and genetic counseling for their families.

Jaringan Saraf Tiruan (JST) Memprediksi Penyakit Rubella Menggunakan Metode Backpropagation

The development of Information Technology is now entering various sectors, including health, and is implemented in Bidadari Binjai Hospital. As a health institution that is committed to excellent service and quality, Bidadari Binjai Hospital needs to innovate technology. One health issue that requires attention is rubella, an airborne infectious disease that has the potential to cause serious disorders such as hearing loss, cataracts, speech delay, and heart failure in toddlers and children. The initial symptoms of rubella are often similar to other common diseases, so public understanding of these symptoms is very important for quick treatment. This research aims to develop an information technology-based system that is able to predict rubella using the backpropagation method. This method is expected to improve the accuracy of diagnosis and make it easier for people to recognize rubella symptoms early on. The proposed system aims to provide better diagnosis support at Bidadari Binjai Hospital, as well as increase public awareness and knowledge about rubella disease. From the research conducted, the results of the accuracy rate obtained when conducting a test program were selected according to the symptoms and the results obtained were rubella disease with a 100% accuracy rate.

Strategy of Religious Character Implementation for Special Needs Student at SD Langit Biru Kota Bengkulu

This article examines the strategies used by teachers in integrating religious character for children with special needs at the research location at SD Langit Biru Kota Bengkulu. The aim of this research is to present a reference/learning model for children with special needs which is still very rarely found in research on education. This happens because there are still very few schools that are serious about working on inclusive class programs. Of these few schools, SD Langit Biru, Kota Bengkulu is one of the schools that holds inclusion classes. The method used in this research is descriptive qualitative with a case study approach. Data collection techniques through interviews, observation and documentation. In data analysis, content analysis is used where the results of documentation, interviews and observations are compiled, edited or interpreted .. The results of this research are: First, there are three types of needs of ABK students at SD Langit Biru, Kota Bengkulu, namely, speech delay, Grahita, and Autism. Second , there is no standard character development strategy for children with special needs. Learning strategies are adapted to the type of special needs and are stated in each individual program and according to the achievements of the phases in the independent curriculum. Third, although each has its own individual program. The four obstacles faced by teachers include a lack of knowledge about children with special needs, fluctuating parental commitment and limited facilities. Although this research is a case study in one elementary school and it is very possible that different strategies will be found in other schools, this article presents strategies and learning models in cultivating religious character for children with special needs which can be a reference in developing other learning strategies.