Humans ; Language Development Disorders/diagnosis* ; Early Diagnosis ; Child

OBJECTIVES: To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. METHODS: A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. RESULTS: The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. CONCLUSIONS GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*

Child ; Humans ; Speech ; Physicians, Primary Care ; Language Development Disorders/diagnosis* ; Speech Disorders

OBJECTIVE: To explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (MEDHSIL). METHODS: Two children who had visited the Ningbo Women and Children's Hospital on October 15, 2021 were selected as the study subjects. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were verified by Sanger sequencing of their family members. RESULTS: The two children were respectively found to harbor a heterozygous c.138delC (p.Ile47Serfs*42) variant and a c.833del (p.L278*) variant of the MEF2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION The c.138delC and c.833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children. Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.
Child ; Humans ; Family ; Genetic Counseling ; Language ; MEF2 Transcription Factors/genetics* ; Muscle Hypotonia/genetics* ; Neurodevelopmental Disorders

OBJECTIVE: To explore the clinical and genetic characteristics of a boy with isolated maternal uniparental disomy of chromosome 20 [UPD(20)mat]. METHODS: A child who was admitted to the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology on April 8,2021. was selected as the study subject. Phenotypic and endocrinological findings of the child were retrospectively analyzed. Whole exome sequencing (WES) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were carried out for detecting the UPD sequences and copy number variations. Both of his parents were verified by Sanger sequencing. Relevant literature was systematically reviewed. RESULTS: The child, a 3-year-and-8-month-old boy born to a 41-year-old mother by Cesarean delivery at 36⁺² gestational weeks due to oligohydramia, had a birth weight of 2 300 g and length of 46 cm. He was admitted to the NICU for feeding difficulties which had persisted despite of clinical management. At the age of 3.75, he had a height of 92.5 cm (< 3rd percentile; 25th ~ 50th percentile at 2.5 years) and a weight of 10.8 kg (< 3rd percentile; 50th percentile at 15 months). He had also presented with growth retardation, short stature, attention deficit and hyperactivity disorder (ADHD), mild mental retardation, and speech and language development disorders. He had simian creases in both hands but no additional dysmorphic signs, and his motor development was normal. Serum insulin, thyroid-stimulating hormone, and insulin growth factor binding protein 3 levels were within the normal ranges, though insulin growth factor-1 (IGF-1) was slightly decreased. Since that time he had continuously used atomoxetine hydrochloride capsules to control his ADHD. WES and MS-MLPA revealed the existence of UPD (20)mat. CONCLUSION The UPD(20)mat syndrome is characterized by feeding difficulties, growth retardation and short stature. The child in our case has been accompanied by ADHD and speech and language development disorders, which required long-term treatment. For women with advanced maternal age and suggestive phenotypes, genetic testing and counseling should be conducted.
Male ; Pregnancy ; Humans ; Child ; Female ; Infant ; Adult ; Chromosomes, Human, Pair 20 ; DNA Copy Number Variations ; Retrospective Studies ; Uniparental Disomy/genetics* ; Atomoxetine Hydrochloride ; Dwarfism ; Intercellular Signaling Peptides and Proteins ; Language Development Disorders ; Growth Disorders ; Insulins

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation and speech delay. METHODS: Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy. RESULTS: The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c.5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c.56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c.5314dupA variant of the KAT6A gene in the fetus. CONCLUSION The heterozygous c.5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.
Child ; Humans ; Male ; Pregnancy ; Histone Acetyltransferases ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree

Objective: As part of the thrust towards Universal Health Care, the Philippines has enhanced health insurance coverage for rehabilitation with recent introductions of benefits for disabilities in children, prostheses, and orthoses. The project aimed to develop a functionality-based framework to guide comprehensive benefits for rehabilitation services for adult Filipinos. Methods: Scoping review was conducted to identify common rehabilitation conditions, frameworks for clinical assessment, and essential services for rehabilitation. Key informant interviews and focus group discussions were conducted with targeted rehabilitation service providers and experts to validate the information collected. A unified pathway of care and essential services for the provision of rehabilitation medicine services was developed through triangulation. The study was conducted from October 2018 to September 2019, with activities done in Metro Manila. Results: The results summarized treatment pathways for four major disease categories: neurologic, musculoskeletal, chronic pain, and activities of daily living/ cardiopulmonary. Impairments were identified reflecting the principles from the International Classification of Function. Disabilities were categorized based on function: mobility, self-care, cognitive-behavioral, and communication. A unified care pathway was developed to harmonize rehabilitation assessment, management, and care. A framework to simplify financial coverage was likewise provided. The extent of management (e.g., duration of therapy) depends on the severity of the disability classified as mild, moderate, or severe. Based on this classification, essential management modalities included physiatry interventions, medications, and rehabilitation sessions, supported by outcomes evaluation. Conclusion A framework is proposed to guide the design and implementation of benefits and health insurance coverage. Awareness and application of this approach among rehabilitation practitioners and health facilities are essential steps for successful uptake and implementation of the upcoming expansion in PhilHealth coverage.
Rehabilitation ; Rehabilitation of Speech and Language Disorders ; Neurobehavioral Manifestations ; Cognitive Behavioral Therapy ; Behavioral Symptoms ; Communication Disorders ; Insurance, Major Medical

OBJECTIVE: To describe a family with intellectual developmental disorder with autism and speech delay (IDDAS) caused by a splice variant of TBR1 gene. METHODS: A pregnant women with mental retardation, who also had a family history of mental retardation, was admitted to Prenatal Diagnosis Center of WanBei Coal and Electricity Group General Hospital Corporation in April 2019. Molecular genetic tests were performed on the pregnant women and ten other family members to analyze the pathogenic genotype. Functional assays of the pathogenic variant was carried out by minigene technology. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling. RESULTS: Through whole exome sequencing, a novel splicing variant (c.1129-1G>C) was identified in the TBR1 gene of the proband, which has co-segregated with the disease phenotype in the family. The results of minigene assay showed abnormal splicing of exon 5. The variant was not detected in the fetal amniotic fluid. Fetal growth and development were normal one year after the birth. CONCLUSION The c.1129-1G>C variant of the TBR1 probably underlay the disease in of the pedigree. Timely prenatal genetic diagnosis and consultation can help to stop the transmission of the pathogenic variant.
Autistic Disorder/genetics* ; China ; Developmental Disabilities ; Female ; Humans ; Infant ; Intellectual Disability/genetics* ; Language Development Disorders ; Pedigree ; Pregnancy ; T-Box Domain Proteins/genetics*

OBJECTIVE: To analyze the clinical features and genetic basis of three children with mental retardation, language impairment and autistic features due to de novo variants of FOXP1 gene. METHODS: Clinical data of the children were collected.Trio-whole exome sequencing was carried out for the children and their parents. Pathogenicity of the variants was analyzed through bioinformatics prediction. RESULTS: All of the children had various degrees of mental retardation in conjunct with language deficit, global developmental delay, abnormal behavior and peculiar facial features, among whom two also developed autism spectrum disorders. The results of genetic testing showed that all three children harbored de novo variants of the FOXP1 gene, namely c.613_c.614delCTinsTA, c.1248delC and c.1393A>G. Two of these were frameshift variants and one was missense variant, which were all rated as pathogenic based on the guidelines of the American College of Medical Genetics (ACMG). Database search suggested that c.613_c.614delCTinsTA and c.1248delC were unreported previously. CONCLUSION For the three children from unrelated families with mental retardation in conjunct with language deficit, global growth delay, abnormal behavior and peculiar facial features, the c.613_ c. 614delCTinsTA, c.1248delC and c.1393A>G variants of the FOXP1 gene may be the pathogenic factors. Above cases have further expanded the genotype-phenotype profile of FOXP1 deficiency syndrome.
Autistic Disorder/genetics* ; Child ; Forkhead Transcription Factors/genetics* ; Genetic Testing ; Humans ; Intellectual Disability/genetics* ; Language Development Disorders/genetics* ; Repressor Proteins/genetics* ; Whole Exome Sequencing

OBJECTIVE: To evaluate correlations between values of articulation tests and language tests for children with articulation disorder in Korea. METHODS: Data of outpatients with chief complaint of an articulation problem were retrospectively collected. Patients who underwent Urimal Test of Articulation and Phonation (U-TAP) with Assessment of Phonology and Articulation for Children (APAC), Preschool Receptive-Expressive Language Scale (PRES), or Receptive and Expressive Vocabulary Test (REVT) simultaneously were identified. Patients whose word-level percentages of correct consonants in U-TAP (UTAP_wC) were more than 2 standard deviations below the mean as diagnostic criteria for articulation disorder were selected. Those whose receptive language age (P_RLA), expressive language age (P_ELA), or combined language age (P_CLA) in PRES was delayed more than 24 months compared to their chronological age in months as diagnostic criteria for language disorder were excluded. RESULTS: Thirty-three children aged 3–6 years were enrolled retrospectively. PRES and U-TAP showed significant correlations for most of value relationships. PRES and APAC showed significant correlations for all value relationships except for receptive language age. All values of REVT were significantly correlated with all values from U-TAP, but not with any value from APAC. Articulation tests U-TAP and APAC showed significant correlations between percentages of correct consonants. Language tests PRES and REVT showed significant correlations for all value relationships. CONCLUSION: This study suggests that articulation abilities and language abilities might be correlated in children with articulation disorder.
Articulation Disorders ; Child ; Humans ; Korea ; Language ; Language Disorders ; Language Tests ; Outpatients ; Phonation ; Retrospective Studies ; Speech Articulation Tests ; Speech Disorders