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*

The Autism Spectrum Rating Scale (ASRS) and the Social Responsiveness Scale (SRS) have been widely used for screening autism spectrum disorder (ASD) in the general population during epidemiological studies, but studies of individuals with intellectual disability (ID) are quite limited. Therefore, we recruited the parents/caregivers of 204 ASD cases, 71 ID cases aged 6-18 years from special education schools, and 402 typically developing (TD) children in the same age span from a community-based population to complete the ASRS and SRS. The results showed that the ID group scored significantly lower on total and subscale scores than the ASD group on both scales (P < 0.05) but higher than TD children (P < 0.05). Receiver operating characteristic analyses demonstrated a similar fair performance in discriminating ASD from ID with the ASRS (area under the curve (AUC) = 0.709, sensitivity = 77.0%, specificity = 52.1%, positive predictive value (PPV) = 82.2%) and the SRS (AUC = 0.742, sensitivity = 59.8%, specificity = 77.5%, PPV = 88.4%). The results showed that individuals with ID had clear autistic traits and discriminating ASD from ID cases was quite challenging, while assessment tools such as ASRS and SRS, help to some degree.
Adolescent ; Age Distribution ; Age Factors ; Autism Spectrum Disorder ; complications ; psychology ; Child ; China ; Female ; Humans ; Intellectual Disability ; etiology ; Male ; Psychiatric Status Rating Scales ; Psychometrics ; Retrospective Studies ; Social Behavior ; Statistics, Nonparametric

A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.
Base Sequence ; Developmental Disabilities ; diagnosis ; genetics ; Fingers ; abnormalities ; Humans ; Infant ; Intellectual Disability ; diagnosis ; genetics ; Male ; Microcephaly ; diagnosis ; genetics ; Muscle Hypotonia ; diagnosis ; genetics ; Mutation ; Myopia ; diagnosis ; genetics ; Neutropenia ; complications ; genetics ; psychology ; Obesity ; diagnosis ; genetics ; Psychomotor Disorders ; diagnosis ; etiology ; genetics ; Retinal Degeneration ; diagnosis ; genetics ; Vesicular Transport Proteins ; genetics

OBJECTIVEThis study aimed to explore the association between periconceptional fish consumption by parents and autism spectrum disorder (ASD) and intelligence deficiency (ID).

METHODSA case-control study was conducted through a questionnaire with 108 ASD cases, 79 ID cases, and 108 controls. The ASD and ID cases were students from special educational schools in Tianjin from 2012 to 2014. The age- and sex-matched controls were from a high school, three primary schools, and a kindergarten in Tianjin. Multivariate logistic regression was performed.

RESULTSPaternal habit of eating hairtail before fertilization, maternal preference for fruits during pregnancy, and maternal habit of eating grass carp during pregnancy were preventive factors for ASD. Paternal habit of drinking alcohol before fertilization was a risk factor for ID, whereas maternal preference for fruits during pregnancy and maternal habit of eating crucian carp during pregnancy were protective factors for ID.

CONCLUSIONParental fish consumption is beneficial for the prevention of ASD and ID. Meanwhile, the protective effects of fish consumption on ASD and ID differ. More attention should be paid to the combined effect of other food when eating fish.

Adolescent ; Animals ; Autism Spectrum Disorder ; epidemiology ; etiology ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Diet ; adverse effects ; Environmental Exposure ; Female ; Fishes ; Humans ; Incidence ; Intellectual Disability ; epidemiology ; etiology ; Male ; Maternal Exposure ; Paternal Exposure ; Pregnancy ; Prenatal Exposure Delayed Effects ; epidemiology ; etiology ; Risk Factors ; Species Specificity

This study reports a boy with psychomotor retardation and epilepsy due to maternal phenylketonuria (PKU). The boy was admitted at the age of 20 months because of psychomotor retardation and epilepsy. He had seizures from the age of 1 year. His development quotient was 43. He presented with microcephaly, normal skin and hair color. Brain MRI scan showed mild cerebral white matter demyelination, broadening bilateral lateral ventricle and foramen magnum stricture. Chromosome karyotype, urine organic acids, blood amino acids and acylcarnitines were normal. His mother had mental retardation from her childhood. She presented with learning difficulties and yellow hair. Her premarriage health examinations were normal. She married a healthy man at age of 26 years. When she visited us at 28 years old, PKU was found by markedly elevated blood phenylalanine (916.54 μmol/L vs normal range 20-120 μmol/L). On her phenylalanine hydroxylase (PAH) gene, a homozygous mutations c.611A>G (p.Y204C) was identified, which confirmed the diagnosis of PAH-deficient PKU. Her child carries a heterozygous mutation c.611A>G with normal blood phenylalanine. Her husband had no any mutation on PAH. It is concluded that family investigation is very important for the etiological diagnosis of the children with mental retardation and epilepsy. Carefully clinical and metabolic survey should be performed for the parents with mental problems to identify parental diseases-associated child brain damage, such as maternal PKU.
Adult ; Epilepsy ; etiology ; Female ; Humans ; Infant ; Intellectual Disability ; etiology ; Male ; Phenylalanine Hydroxylase ; genetics ; Phenylketonuria, Maternal ; Pregnancy

OBJECTIVETo analyze a case of cerebrotendinous xanthomatosis (CTX) with mental retardation as the initial neurological symptom.

METHODSMedical imaging, histopathological assay and genetic testing were carried out to analyze the patient.

RESULTSNeurological manifestations of the 27-year-old male patient were initiated by mental retardation and subsequently memory lapses, ataxia, spastic paraplegia and fuzzy language. Other symptoms included cataract, xanthomatosis in Achilles tendon, kidney stones and high arches. The total bile acid in serum has risen to 14.7 umol/L. There were symmetrical abnormal signals in bilateral cerebellar dentate nuclei, hypointensities on T1WI and DWI and mixed signals on T2WI. Cholesterol crystallization and cholesterol granulomatous inflammation were found upon pathological examination of the Achilles tendon. The patient was found to have carried a compound heterozygous mutation of the CTX gene, which consisted of two novel mutations including c.379C>T (p.Arg127Trp) in exon 2 and c.1174G>A (p.Glu392Lys) in exon 6 of the CYP27A1 gene.

CONCLUSIONClinicians should be alert to cerebrotendinous xanthomatosis when the patient has mental retardation caused by genetic and metabolic factors beginning at a young age, particularly accompanied with tendinous xanthomatosis and cataracts. CTX can be readily diagnosed by histopathological assay and sequencing of the CYP27A1 gene.

Adult ; Cholestanetriol 26-Monooxygenase ; genetics ; Humans ; Intellectual Disability ; etiology ; Male ; Xanthomatosis, Cerebrotendinous ; complications ; genetics

OBJECTIVETo summarize the clinical features of those Duchenne and Becker muscular dystrophy (DMD and BMD) patients who are complicated with epilepsy, and try to analyze the genotype- phenotype correlation.

METHODBy a retrospective analysis of 307 patients with DMD and BMD who attended Peking University First Hospital from February 2006 to September 2014,7 patients complicated with epilepsy were identified and their clinical data were collected. The possible mechanism of epilepsy in DMD and BMD patients was proposed after analyzing the genotype-phenotype correlation.

RESULT(1) Among 307 DMD and BMD patients, 7 cases had epilepsy, the prevalence was 2. 28%. (2) The age of onset of epilepsy ranged from 8 months to 11 years. Focal seizure was the most common seizure type (6 cases) , while other seizure types were also involved, such as generalized tonic-clonic seizure. As to epilepsy syndromes, 1 boy was diagnosed as benign childhood epilepsy with centrotemporal spikes (BECT). Six patients were treated with 1 or 2 types of antiepileptic drugs and seizures were controlled well. On follow-up, 6 of the 7 children had normal mental development, while the remaining 1 patient was diagnosed as mild mental retardation. (3) DMD gene mutations of all 7 patients were analyzed. Exons deletions were found in 6 cases while point mutation was found in 1 case.

CONCLUSIONThe prevalence of epilepsy in DMD and BMD patients was higher than the prevalence in normal population. The age of onset of epilepsy varies, and focal seizure may be the most common seizure type. Some patients may also present as some kind of epilepsy syndrome, such as BECT. In most patients, seizures can be controlled well by 1 or 2 types of antiepiletic drugs. No clear correlation was found between genotype and phenotype in DMD and BMD patients who were complicated with epilepsy, probably due to limited number of cases.

Anticonvulsants ; therapeutic use ; Child ; Epilepsy ; complications ; drug therapy ; epidemiology ; Exons ; Genotype ; Humans ; Intellectual Disability ; etiology ; Male ; Muscular Dystrophy, Duchenne ; complications ; genetics ; Mutation ; Phenotype ; Prevalence ; Retrospective Studies ; Seizures ; Sequence Deletion

Intellectual disability, occurring in 1%-3% of the general population, is a common disease of the nervous system in children. Since diverse genetic and environmental factors contribute to its pathogenesis, the etiological diagnosis of intellectual disability is challenging with respect to the selection of diagnostic tests. It is important to determine the etiology of intellectual disability for the assessment of prognosis, treatment and the family plan. This paper summarizes the research progress in etiology and diagnosis for intellectual disability and introduces the recommended clinical genetics diagnostic approach from the American Academy of Pediatrics.
Chromosome Banding ; High-Throughput Nucleotide Sequencing ; Humans ; Intellectual Disability ; diagnosis ; etiology ; genetics ; Microarray Analysis

OBJECTIVETo study the clinical characteristics and diagnostic methods of rare autosomal recessive inherited Bardet-Biedl syndrome in patients presented with renal abnormalities.

METHODComprehensive analyses were performed on data of 4 confirmed Bardet-Biedl syndrome cases seen at nephrology department of Beijing Children Hospital affiliated to Capital Medical University, including clinical features, laboratory examination and diagnostic criteria.

RESULT(1) Four cases were confirmed to meet Bardet-Biedl syndrome diagnostic criteria (male: female = 1: 1): first diagnosis age was 10 y, 9 y 8 m, 10 y 10 m, 8 y 2 m. (2) Cases 1, 2, and 3 had a history of polyuria and polydipsia, cases 4 began with edema and oliguria. (3) All had slight change in urine routine test. Case 3 and Case 4 were presented with small to medium amount of proteinuria. None had microscopic hematuria. (4) All had different degree of renal injury, Case 1 and 3 were at the third phase of chronic kidney disease (CKD), Case 4 was at the fourth phase of CKD, Case 4 was at the fifth phase of CKD and needed dialysis. (5) All cases had obvious abnormalities of urinary tract ultrasound, 3 of them had chronic diffuse lesions with cyst formation of both kidneys. The rest one had dysplasia of right kidney and fused kidney. (6) All cases were presented with vision loss with 100% of electroretinogram abnormalities and 50% of fundus examination abnormalities. (7) Three cases were presented with obesity. (8) Multiple organs were involved in all cases, including electrocardiographic abnormality and/or thickening of the left ventricular wall (4/4) , polydactyly (2/4) , small penis and testicles (2/4) and short stature (2/4) .

CONCLUSIONClinical manifestations of Bardet-Biedl syndrome (BBS) conceals, routine urine test changes slightly, abnormalities of renal structure and (or) tubular interstitial function is a typical manifestation of children with BBS. Urinary tract ultrasound screening may show diffuse lesions with double kidney with cyst formation or structural abnormalities. Clinical manifestation accompany with retinal degeneration, obesity, myocardial involvement, polydactyly, and hypogonadism.

Abnormalities, Multiple ; Bardet-Biedl Syndrome ; complications ; diagnosis ; pathology ; Biomarkers ; blood ; urine ; Child ; Female ; Humans ; Intellectual Disability ; Kidney ; abnormalities ; diagnostic imaging ; Kidney Diseases ; diagnosis ; etiology ; pathology ; Male ; Renal Insufficiency ; etiology ; pathology ; Retinal Diseases ; etiology ; pathology ; Tomography, X-Ray Computed ; Ultrasonography, Doppler, Color

OBJECTIVETo analyze clinical characteristics of a combination of dystrophinopathies and Klinefelter's syndrome (karyotype 47, XXY) in one patient.

METHODThe patient was diagnosed as Duchenne muscular dystrophy (DMD) and Klinefelter's syndrome in Beijing Children's Hospital in March, 2013. The clinical manifestations, physical examinations and laboratory test results were analyzed respectively. The clinical characteristics of four cases reported previously were analyzed as well.

RESULTThe 8.5 years old boy presented with symptoms of walking disorder and developmental delay. The patient had facial dysmorphism, waddling gait, Gower's manoeuvre and enlarged calves.Serum creatine kinase level was 21 040 U/L, and he had mild intellectual impairment. Deletions of exons 49-54 of the dystrophin gene were found.Gene dosage analysis revealed a heterozygous deletion in his mother. Five cases have been reported till now, their age ranged from 3.5 to 18 years; 3 of them were DMD, while the other 2 cases were Becker muscular dystrophy (BMD). One of them, detected in pedigree study, whose weakness was minimal in contrast to the proband. The others came to the hospital because of walking disorder or developmental delay. All the patients had enlarged calves, some of them also had Gower's manoeuvre and waddling gait. The patients' height was between 3 rd and 50 th percentile, while 2 of them had facial dysmorphism.Some degree of mental impairment is usual. Their serum creatine kinase were 2 469-24 750 U/L.One of them was detected in pedigree study. Three of them were diagnosed by muscle biopsy, while in the other one mutation analysis was used.

CONCLUSIONThe combination of dystrophinopathies and Klinefelter's syndrome is quite rare, and has clinical features of these two diseases. Mutation analysis (or muscle biopsy) and karyotype analysis can finally diagnose the syndrome.

Child ; Creatine Kinase ; blood ; DNA Mutational Analysis ; Dystrophin ; genetics ; metabolism ; Exons ; genetics ; Gene Deletion ; Heterozygote ; Humans ; Intellectual Disability ; Klinefelter Syndrome ; complications ; diagnosis ; genetics ; Male ; Muscle Weakness ; etiology ; Muscular Dystrophy, Duchenne ; complications ; diagnosis ; genetics ; Mutation ; Pedigree