Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.
Male ; Female ; Humans ; Child, Preschool ; Child ; Neurofibromatosis 1/diagnosis* ; Retrospective Studies ; Intellectual Disability ; Electroencephalography ; Epilepsy/etiology* ; Seizures/etiology*

OBJECTIVE: To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. METHODS: An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). RESULTS: The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother. CONCLUSION The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Humans ; Infant ; Male ; alpha-Thalassemia/diagnosis* ; Ataxia Telangiectasia Mutated Proteins/genetics* ; East Asian People ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/diagnosis* ; Pedigree ; X-linked Nuclear Protein/genetics*

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation, language delay and autism. METHODS: G-banding chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were carried out for the child and her parents. RESULTS: The child was found to have a 46,XX,dup(8p?) karyotype, for which both of her parents were normal. SNP-array revealed that the child has harbored a 6.8 Mb deletion in 8p23.3p23.1 and a 21.8 Mb duplication in 8p23.1p12, both of which were verified as de novo pathogenic copy number variants. CONCLUSION The clinical features of the child may be attributed to the 8p deletion and duplication. SNP-array can facilitate genetic diagnosis for children featuring mental retardation in conjunct with other developmental anomalies.
Humans ; Child ; Pregnancy ; Female ; Intellectual Disability/genetics* ; Prenatal Diagnosis ; Karyotyping ; Chromosome Banding ; Chromosome Deletion

OBJECTIVES: To summarize the clinical phenotype and genetic characteristics of children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations. METHODS: A retrospective analysis was performed on the medical data of 8 children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University. RESULTS: The mean age of onset was 9 months for the 8 children. All children had moderate-to-severe developmental delay (especially delayed language development), among whom 7 children also had seizures. Among these 8 children, 7 had novel heterozygous mutations (3 with frameshift mutations, 2 with nonsense mutations, and 2 with missense mutations) and 1 had 6p21.3 microdeletion. According to the literature review, there were 48 Chinese children with mental retardation caused by SYNGAP1 gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy. CONCLUSIONS Children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.
Child ; Humans ; Intellectual Disability/diagnosis* ; Codon, Nonsense ; Retrospective Studies ; Valproic Acid ; ras GTPase-Activating Proteins/genetics* ; Mutation ; Seizures/genetics*

OBJECTIVE: To explore the clinical features and genetic basis for a child with Bainbridge-Ropers syndrome (BRPS). METHODS: Clinical data of the child were retrospectively analyzed. Copy number variation sequencing (CNV-seq) and trio based whole exome sequencing (trio-WES) were carried out. Prenatal diagnosis was provided for a at risk fetus from the pedigree, and genotype phenotype correlation was summarized through a literature review. RESULTS: The proband, a 6-year-old boy, has presented with feeding difficulties, specific craniofacial features, global developmental delay and intellectual disability, which has not improved after rehabilitation treatment. CNV-seq analysis of the patient showed no obvious abnormalities. A de novo heterozygous truncating variation, c.1448dupT (p.T484Nfs*5), was identified in the ASXL3 gene by trio-WES, which was a previously reported pathogenic variant. So far 14 Chinese patients with BRPS and ASXL3 variants have been reported. All patients have shown specific craniofacial features and delayed motor and speech development, and harbored 12 loss of function ASXL3 variants, which were de novo in origin and have clustered in exons 11 and 12 of the ASXL3 gene. CONCLUSION The heterozygous frameshift c.1448dupT (p.T484Nfs*5) variant of the ASXL3 gene probably underlay the disorder in this patient. BRPS should be considered in infants with feeding difficulties, special craniofacial features, global developmental delay and hand anomalies, and WES can help to delineate the pathogenesis and establish the definite diagnosis.
Child ; Humans ; Female ; Pregnancy ; Developmental Disabilities/genetics* ; Phenotype ; Pedigree ; DNA Copy Number Variations ; Retrospective Studies ; Transcription Factors/genetics* ; Syndrome ; Intellectual Disability/genetics* ; Prenatal Diagnosis ; China

OBJECTIVE: To analyze the (CGG)n repeats of FMR1 gene among patients with unexplained mental retardation. METHODS: For 201 patients with unexplained mental retardation, the (CGG)n repeats of the FMR1 gene were analyzed by PCR and FragilEase RESULTS: For the 201 patients with unexplained mental retardation, 15 were identified with full mutations of the FMR1 gene. The prevalence of fragile X syndrome (FXS) in patients with unexplained mental retardation was determined as 7.5% (15/201). Prenatal diagnosis was provided for 6 pregnant women with pre- or full mutations. Analysis revealed that women with mental retardation and full FMR1 mutations exhibited a skewed XCI pattern with primary expression of the X chromosome carrying the mutant allele. CONCLUSION FXS has a high incidence among patients with unexplained mental retardation. Analysis of FMR1 gene (CGG)n repeats in patients with unexplained mental retardation can facilitate genetic counseling and prenatal diagnosis for their families. FMR1 gene (CGG)n repeats screening should be recommended for patients with unexplained mental retardation.
Female ; Fragile X Mental Retardation Protein/genetics* ; Fragile X Syndrome/genetics* ; Humans ; Intellectual Disability/genetics* ; Mutation ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in patients with intellectual disability/developmental delay(ID/DD). METHODS: SNP array was performed to detect genome-wide DNA copy number variants (CNVs) for 145 patients with ID/DD in Women's Hospital, Zhejiang University School of Medicine from January 2013 to June 2018. The CNVs were analyzed by CHAS software and related databases. RESULTS: Among 145 patients, pathogenic chromosomal abnormalities were detected in 32 cases, including 26 cases of pathogenic CNVs and 6 cases of likely pathogenic CNVs. Meanwhile, 18 cases of uncertain clinical significance and 14 cases of likely benign were identified, no significant abnormalities were found in 81 cases (including benign). CONCLUSIONS SNP array is effective for detecting chromosomal abnormalities in patients with ID/DD with high efficiency and resolution.
Chromosome Aberrations ; DNA Copy Number Variations ; Genome-Wide Association Study ; Humans ; Intellectual Disability ; diagnosis ; genetics ; Oligonucleotide Array Sequence Analysis ; standards ; Polymorphism, Single Nucleotide

Tatton-Brown-Rahman Syndrome (TBRS), an overgrowth syndrome caused by heterozygous mutation of DNMT3A, first was described in 2014. Approximately 60 DNMT3A variants, including 32 missense variants, have been reported, with most missense mutations located on the DNMT3A functional domains. Autosomal dominant inheritance by germ-line mutation of DNMT3A has been reported, but vertical transmission within a family is extremely rare. Herein, we report the first Korean family with maternally inherited TBRS due to the novel heterozygous DNMT3A variant c.118G>C p.(Glu40Gln), located outside the main functional domain and identified by multigene panel sequencing. The patient and her mother had typical clinical features, including tall stature during childhood, macrocephaly, intellectual disability, and characteristic facial appearance. TBRS shows milder dysmorphic features than other overgrowth syndromes, potentially leading to underdiagnosis and underestimated prevalence; thus, targeted multigene panel sequencing including DNMT3A will be a useful tool in cases of overgrowth and unexplained mild intellectual disability for early diagnosis and genetic counseling.
Early Diagnosis ; Genetic Counseling ; Germ-Line Mutation ; Growth Disorders ; High-Throughput Nucleotide Sequencing ; Humans ; Intellectual Disability ; Megalencephaly ; Mothers ; Mutation, Missense ; Prevalence ; Sequence Analysis, DNA ; Wills

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare, autosomal recessive disorder; affected patients are characterized by inability to feel pain and to sweat over the entire body, as well as by mental retardation. Because, in the oral examination, no specific findings on soft or hard tissue may be found except possible lesions due to self-mutilation, early recognition and diagnosis are essential for these patients. Pediatric dentists must be aware of the clinical manifestations and treatment considerations related to uncontrolled body temperature, tactile hyperesthesia and lack of pain reflex. In this case report, dental management of CIPA was suggested by presenting a 6-year follow-up of young patient.
Body Temperature ; Dentists ; Diagnosis ; Diagnosis, Oral ; Follow-Up Studies ; Hereditary Sensory and Autonomic Neuropathies ; Humans ; Hyperesthesia ; Hypohidrosis ; Intellectual Disability ; Pain Insensitivity, Congenital ; Reflex ; Sweat

OBJECTIVE: To assess the value of combined cytogenetic and molecular techniques for the prenatal diagnosis of a pregnant woman with intellectual disability (ID). METHODS: The fetus and its parents were subjected to G-banding karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) analysis. RESULTS: G-banding karyotype analysis revealed that the woman has carried a chromosomal microdeletion 46,XX,del(11)(q24), and the fetus was a carrier of 46,XN,del(11)(q24)mat. Subsequent SNP-array and FISH analysis of the pregnant woman indicated that the microdeletion has mapped to 11q24.1-q25. Both the pregnant woman and her fetus were diagnosed with Jacobsen syndrome. CONCLUSION Combined use of cytogenetic and molecular genetic techniques can facilitate diagnosis of patients with intellectual disability.
Chromosome Deletion ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; Jacobsen Distal 11q Deletion Syndrome ; diagnosis ; Karyotyping ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis