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

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

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: 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

KBG syndrome is a rare neurodevelopmental disorder characterized by intellectual disability, skeletal anomalies, short stature, craniofacial dysmorphism, and macrodontia. ANKRD11 gene mutation and 16q24.3 microdeletion have been reported to cause KBG syndrome. Here, we report two patients with ANKRD11 mutations who initially presented with neurologic symptoms such as developmental delay and seizures. Patient 1 was a 23-month-old boy who presented with a global developmental delay. Language delay was the most dominant feature. He had hypertelorism, hearing impairment, and behavior problems characterized as hyperactivity. A c.1903_1907delAAACA (p.Lys635GInfsTer26) mutation in ANKRD11 was identified with diagnostic exome sequencing. Patient 2 was a 14-month-old boy with developmental delay and seizure. He also had atrial septum defect, and ventricular septal defect. Generalized tonic seizures began at the age of 8 months. Electroencephalography showed generalized sharp and slow wave pattern. Seizures did not respond to antiepileptic drugs. A loss of function mutation c.5350_5351delTC (p.ser1784HisfsTer12) in ANKRD11 was identified with diagnostic exome sequencing. In both cases, characteristic features of KBG syndrome such as short stature or macrodontia, were absent, and they visited the hospital due to neurological symptoms. These findings suggest that more patients with mild phenotypes of KBG syndrome are being recognized with advances in diagnostic exome sequencing genetic technologies.
Anticonvulsants ; Atrial Septum ; Developmental Disabilities ; Early Diagnosis* ; Electroencephalography ; Exome* ; Hearing Loss ; Heart Septal Defects, Ventricular ; Humans ; Hypertelorism ; Infant ; Intellectual Disability ; Language Development Disorders ; Male ; Neurodevelopmental Disorders ; Neurologic Manifestations ; Phenotype ; Seizures

The paper describes the validation of the Malay Preschool Language Assessment Tool (MPLAT), a standardized normed referenced language assessment tool for Malay preschoolers within the ages of 4;0-6;11 and whose native language is Malay. The MPLAT (A Razak et al. 2010) is an assessment tool which is designed to assess the areas of receptive language, expressive language and early literacy skills. The MPLAT contains six subtests i.e. picture vocabulary, grammatical understanding, sentence repetition, referential meaning, relational meaning and early literacy skills. This paper is divided into 2 studies. Study 1 tested the psychometric properties and normative data of the diagnostic version of MPLAT on 300 participants recruited from preschools in the rural area of Gua Musang and the urban area of Kota Bahru located in the East Coast state of Kelantan. The construct validity is high with a strong correlation (r = 0.942) between test scores and age, validating the developmental nature of the test. There was also moderate to strong positive correlation between each subtest and the test total, as well as between subtests. It also has high test-retest reliability (r = 0.998 (p < 0.01) and inter-rater reliability (rho = 1.000). The second study looked at the psychometrics properties of the MPLAT short version (screening) compared to the full version diagnostic. The short version of MPLAT is about a quarter of the full (diagnostic) version. About 108 subjects in the urban area of the the Klang Valley, consisting of Kuala Lumpur and Selangor, were administered both versions of the MPLAT. The Pearson correlation revealed a strong positive correlation between the total scores and age (r = 0.718, p<.01), and strong positive correlation for the test-retest reliability (r = 0.881, n=12) for the short MPLAT version. For the full version, the Spearman correlation revealed a strong positive correlation between total scores and age (r = 0.791, p<.01) and a very strong positive Pearson correlation for test-retest reliability (r = 0.943). Cronbach's Alpha values demonstrated the internal consistency of the full version (0.972) and short version (0.929). In summary, both versions of the MPLAT were found to be valid tools to screen and diagnose language problems among Malay preschool children in Malaysia. MPLAT also has the potential to be a useful research tool to delineate language development of the preschool Malay children.
Malay Preschool Language Assessment Tool (MPLAT) ; screening tool ; diagnostic tool ; language assessment ; Malay preschool children ; test development ; test validation

BACKGROUND AND OBJECTIVES: Children who received cochlear implants (CIs) in early age can achieve age-appropriate language ability and can be educated in the classroom alongside normal hearing (NH) peers. However, what is rarely investigated is their relations with NH peers in the classroom. The purpose of this study was to examine the peer relations of children with CIs. SUBJECTS AND METHOD: Peer relations were examined using a peer relation scale test that included support, intimacy, recognition, conflict, and competition. Participants were 25 children who received their first CI before 3.5 years of age. Their peer relations were compared with those of 129 children with NH. RESULTS: Children with CIs evaluated themselves as having good peer relations, but their perception of peer relations varied according to gender and language ability. CI boys with language delay perceived lack of support and intimacy, whereas CI girls with language delay perceived more conflict than NH children. On the other hand, CI children with normal language ability showed no differences in their peer relations from NH children. CONCLUSION: Early CI surgery and intensive language rehabilitation can prevent peer problems and promote adjustment in school life for children with CI.
Child* ; Cochlear Implants* ; Female ; Hand ; Hearing ; Humans ; Language ; Language Development Disorders ; Methods ; Rehabilitation

Floating-Harbor syndrome is a rare autosomal dominant genetic disorder associated with SRCAP mutation. To date, approximately 50 cases of Floating-Harbor syndrome have been reported, but none have been reported in Korea yet. Floating-Harbor syndrome is characterized by delayed bony maturation, unique facial features, and language impairment. Here, we present a 6-year-old boy with a triangular face, deep-set protruding eyes, low-set ears, wide nose with narrow nasal bridge, short philtrum, long thin lips, clinodactyly, and developmental delay that was transferred to our pediatric clinic for genetic evaluation. He showed progressive delay in the area of language and cognition-adaption as he grew. He had previously undergone chromosomal analysis at another hospital due to his language delay, but his karyotype was normal. We performed targeted exome sequencing, considering several syndromes with similar phenotypes. Library preparation was performed with the TruSight One sequencing panel, which enriches the sample for about 4,800 genes of clinical relevance. Massively parallel sequencing was conducted with NextSeq. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the first Korean case of Floating-Harbor syndrome with a novel SRCAP (Snf2 related CREBBP activator protein) mutation (c.7732dupT, p.Ser2578Phefs*6), resulting in early termination of the protein; it was not found in either of his healthy parents or a control population. To our knowledge, this is the first study to describe a boy with Floating-Harbor syndrome with a novel SRCAP mutation diagnosed by targeted exome sequencing in Korea.
Child ; Ear ; Exome* ; High-Throughput Nucleotide Sequencing ; Humans ; Karyotype ; Korea ; Language Development Disorders ; Lip ; Male ; Nose ; Parents ; Phenotype

BACKGROUND AND OBJECTIVES: The present study aimed to compare receptive and expressive language development in children who have undergone simultaneous bilateral cochlear implantation (SCI) and those who have undergone bimodal stimulation (unilateral CI+ hearing aid). SUBJECTS AND METHOD: In a retrospective analysis of clinical data, 15 pediatric patients who have received SCI and nine patients who have received bimodal stimulation (BM group) were enrolled. CI was performed for all patients at 24 months of age. Category of Auditory Performance (CAP) scores, Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) scores, and developmental quotients (DQ) for expressive and receptive language were compared between the groups at 12 month of follow-up. The Percentage of Consonants Correct (PCC) of children evaluated at 4 years old was also compared. RESULTS: At 12 months of follow-up, significantly greater improvements in CAP scores (Δ4.25±0.5) were noted in the SCI group compared to the BM group (Δ3.56±0.88, p=0.041). Significantly greater improvements in IT-MAIS scores were also noted in the SCI group (Δ36.17±4.09) than in the BM group (Δ30.17±2.91, p=0.004). The DQ of receptive language was higher in the SCI group than in the BM group (87.6±15.4% vs. 75.5±12.0%, p=0.023) at 12 months of follow-up. Moreover, early SCI was associated with better receptive language skills. PCC index of children at 4 years old was higher in the SCI group than in the BM group (88.5±13.2% vs. 62±15.8%, p=0.014). Earlier SCI was associated with even greater improvements. CONCLUSION: Bilateral SCI is associated with significant improvements in language development when compared with bimodal stimulation. Earlier SCI was associated with better outcomes.
Child ; Cochlear Implantation ; Cochlear Implants ; Follow-Up Studies ; Hearing ; Humans ; Language Development ; Linguistics* ; Methods ; Retrospective Studies