scholarly journals Phenotypes in Children With SYNGAP1 Encephalopathy in China

2021 ◽  
Vol 15 ◽  
Author(s):  
Huiting Zhang ◽  
Liu Yang ◽  
Jing Duan ◽  
Qi Zeng ◽  
Li Chen ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Behavioral Problems ◽  
Disease Onset ◽  
Gene Mutations ◽  
Global Developmental Delay ◽  
Clinical Trial Registry ◽  
Neurodevelopmental Delay ◽  
Epileptic Spasms ◽  
Registration Number ◽  
Drug Resistant Epilepsy

Objective: We aimed to explore the associated clinical phenotype and the natural history of patients with SYNGAP1 gene variations during early childhood and to identify their genotype–phenotype correlations.Methods: This study used a cohort of 13 patients with epilepsy and developmental disorder due to SYNGAP1 mutations, namely, 7 patients from Shenzhen Children’s Hospital between September 2014 and January 2020 and 6 patients from previously published studies. Their clinical data were studied.Results: A total of 13 children with SYNGAP1 gene variants (eight boys and five girls) were identified. The age of disease onset was in infancy. Mutations were located between exons 8 and 15; most were frameshift or truncated mutations. Four mutation sites (c.924G > A, c.1532-2_1532del, c.1747_1755dup, and c.1735_1738del) had not been reported before. All patients had global developmental delay within the first year of life, and intellectual impairment became gradually apparent. Some of them developed behavioral problems. The developmental delay occurred before the onset of seizures. All seven patients in our cohort presented with epilepsy; myoclonic seizures, absence seizures, and epileptic spasms were the most common seizure types. Abnormal electroencephalograms were identified from five patients before the onset of their seizures. All patients suffered from drug-resistance seizures. However, comorbidities such as behavioral problems were less frequently observed.Conclusion: The most common age of disease onset in SYNGAP1 gene mutations is in infancy, while neurodevelopmental delay and epilepsy are the major phenotypes. They have a higher percentage of drug-resistant epilepsy and epileptic spasms than those in previous reports. We should give attention to the patients with abnormal EEGs without seizures and think about the suitable time of the anti-seizure medications for them. We have not found the genotype–phenotype correlation.Trial registration: Chinese Clinical Trial Registry, Registration number: ChiCTR2100049289 (https://www.chictr.org.cn/listbycreater.aspx).

The Fault in Their Stars—Accumulating Astrocytic Inclusions Associated With Clusters of Epileptic Spasms in Children With Global Developmental Delay

2017 ◽  
Vol 73 ◽  
pp. 92-97.e3 ◽  
Author(s):  
Robyn Whitney ◽  
Sameer AlMehmadi ◽  
Bláthnaid McCoy ◽  
Ivanna Yau ◽  
Ayako Ochi ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Global Developmental Delay ◽  
Epileptic Spasms

Alternating Hemiplegia of Childhood in an Infant with Symptoms Resembling Glucose Transporter 1 Deficiency

2017 ◽  
Vol 15 (04) ◽  
pp. 180-182
Author(s):  
Mini Sreedharan ◽  
Shiji Chalipat ◽  
Kunju Mohammed ◽  
Kalpana Devadathan
Keyword(s):  
Developmental Delay ◽  
Glucose Transporter ◽  
Gene Mutations ◽  
Deficiency Syndrome ◽  
Global Developmental Delay ◽  
Glucose Transporter 1 ◽  
Alternating Hemiplegia Of Childhood ◽  
Slc2a1 Gene ◽  
Glut1 Deficiency ◽  
Atp1a3 Gene

AbstractGlucose transporter type 1 (glut1) deficiency syndrome presents with developmental delay, microcephaly, and recurrent seizures during infancy, as well as cerebrospinal fluid (CSF) hypoglycorrhachia and mutations in the SLC2A1 gene. We describe a baby with microcephaly, global developmental delay, seizures from 3 months of age, and CSF glucose in the lower limit of normal range, with heterozygous p.Glu815Lys mutation of the ATP1A3 gene and no mutation in the SLC2A1 gene. Mutations in ATP1A3 gene are associated with alternating hemiplegia of childhood (AHC). Interestingly the baby developed episodes of recurrent bouts of alternating hemiplegia from 13 months of age. The case is reported to highlight ATP1A3 mutation as a probable etiology for glut1 deficiency like syndrome and AHC. A brief review of literature emphasizing the overlapping paroxysmal and nonparoxysmal symptoms of the two conditions is also included.

scholarly journals Clinical and Genetic Characteristics and Prenatal Diagnosis of Rare Monogenic Global Developmental Delay and Intellectual Disability.

2020 ◽  
Author(s):  
Liling Lin ◽  
Ying Zhang ◽  
Hong Pan ◽  
Jingmin Wang ◽  
Yu Qi ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Prenatal Diagnosis ◽  
Developmental Delay ◽  
Hot Spot ◽  
Disease Onset ◽  
Genetic Diagnosis ◽  
Global Developmental Delay ◽  
Genetic Characteristics ◽  
Pathogenic Variants

Abstract Background: The estimated worldwide prevalence of global developmental delay (GDD) and intellectual disability (ID) is 1-3%. Rare monogenic GDD/ID is poorly characterized because its low prevalence limits research. In this study, we aimed to describe the diagnostic courses and clinical and genetic characteristics of a cohort with rare monogenic GDD/ID.Method:We retrospectively analyzed the diagnostic courses, clinical characteristics, and genetic spectra of rare monogenic GDD/ID patients. We also conducted a follow-up study on prenatal diagnosis in these families. Mutation pathogenicity was interpreted by molecular geneticists and clinicians according to the guidelines of the American College of Medical Genetics and Genomics. Results:Among 108 patients with rare monogenic GDD/ID, it often took 0.5-4 years and 3-5 referrals to obtain a genetic diagnosis after disease onset. Onset typically occurred before 6 years of age, and patients usually presented moderate to severe GDD/ID. The most common coexisting conditions were epilepsy (68%), facial dysmorphism (14%) and microcephaly (13%). In total, 149 different pathogenic variants were found in 81 different genes among the 108 pedigrees, and 71 variants were novel. The most common inheritance patterns in this outbred Chinese population were autosomal recessive (AR; 46.3%), autosomal dominant (AD; 37%), and X-linked (XL; 16.7%). GLB1, PLA2G6, SCN2A, SHANK3 and STXBP1 were important causal genes. Hot-spot mutations were rarely found. By the follow-up, 43 families, including 24 ARID, 13 ADID and 6 XLID families, had undergone prenatal diagnosis. The offspring of 6 ARID, 2 ADID and 2 XLID families had the same pathogenic variants as the probands.Conclusion:Rare monogenic GDD/ID is characterized by early onset, relatively severe symptoms, great clinical variability and genetic heterogeneity. Moreover, timely referrals to genetic counseling and prenatal diagnostic laboratories are important for affected families planning to have additional children.

scholarly journals Atypical NF1 Microdeletions: Challenges and Opportunities for Genotype/Phenotype Correlations in Patients with Large NF1 Deletions

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1639
Author(s):  
Hildegard Kehrer-Sawatzki ◽  
Ute Wahlländer ◽  
David N. Cooper ◽  
Victor-Felix Mautner
Keyword(s):  
Developmental Delay ◽  
Cognitive Abilities ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Neurofibromatosis Type ◽  
Global Developmental Delay ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Nf1 Gene

Patients with neurofibromatosis type 1 (NF1) and type 1 NF1 deletions often exhibit more severe clinical manifestations than patients with intragenic NF1 gene mutations, including facial dysmorphic features, overgrowth, severe global developmental delay, severe autistic symptoms and considerably reduced cognitive abilities, all of which are detectable from a very young age. Type 1 NF1 deletions encompass 1.4 Mb and are associated with the loss of 14 protein-coding genes, including NF1 and SUZ12. Atypical NF1 deletions, which do not encompass all 14 protein-coding genes located within the type 1 NF1 deletion region, have the potential to contribute to the delineation of the genotype/phenotype relationship in patients with NF1 microdeletions. Here, we review all atypical NF1 deletions reported to date as well as the clinical phenotype observed in the patients concerned. We compare these findings with those of a newly identified atypical NF1 deletion of 698 kb which, in addition to the NF1 gene, includes five genes located centromeric to NF1. The atypical NF1 deletion in this patient does not include the SUZ12 gene but does encompass CRLF3. Comparative analysis of such atypical NF1 deletions suggests that SUZ12 hemizygosity is likely to contribute significantly to the reduced cognitive abilities, severe global developmental delay and facial dysmorphisms observed in patients with type 1 NF1 deletions.

scholarly journals 10. Cerebral hyaline astrocytic inclusions in treatment-resistant epilepsy and global developmental delay

2015 ◽  
Vol 42 (S2) ◽  
pp. S4-S5
Author(s):  
M. Signaevski ◽  
C. Sanguansermsri ◽  
M. Connolly ◽  
LN. Hazrati ◽  
C. Dunham
Keyword(s):  
Developmental Delay ◽  
Resection Margin ◽  
Seizure Activity ◽  
Chromosomal Microarray ◽  
Global Developmental Delay ◽  
Treatment Resistant ◽  
Partial Deletion ◽  
Brain Anomalies ◽  
Epileptic Spasms ◽  
Patients With Epilepsy

Cerebral hyaline astrocytic inclusions (HAI) have been observed in a subset of patients with epilepsy, structural brain anomalies, and developmental delay. We present a case of a 2.5-year-old male with epilepsy and global developmental delay. Chromosomal microarray detected a copy loss at 22q13 that resulted in a partial deletion of SHANK3 gene. The EEGs revealed seizure activity arising from left frontal central region. Invasive video electrocorticography captured clusters of epileptic spasms, all originating from left antero-lateral frontal lobe rostral to the motor cortex. We utilized routine histology to identify the inclusions and mapped their distribution in the resected portion of the cortex against electrocorticographic data. Histologic analysis revealed the presence of HAI in the posterio-medial portion of the resected cortex, which corresponded to the site of seizure generalization. HAI were present at the resection margin. Immunohistochemistry was largely non-contributory. HAI is a rare but emerging entity that is associated with epilepsy. To our knowledge, the distribution of inclusions in HAI has never been mapped to electrophysiologic data. In our case, seizure generalization correlated with the inclusions distribution. This suggests that the inclusions may: 1) play a role in epileptogenesis; or, 2) be a biomarker of disease distribution. Finally, the presence of the HAI at the resection margin may foreshadow future seizure activity in this patient.

scholarly journals Oxycodone versus morphine for analgesia after laparoscopic endometriosis resection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lijun Niu ◽  
Lihong Chen ◽  
Yanhua Luo ◽  
Wenkao Huang ◽  
Yunsheng Li
Keyword(s):  
Respiratory Depression ◽  
Visceral Pain ◽  
Deep Infiltrating Endometriosis ◽  
Trial Registry ◽  
Clinical Trial Registry ◽  
Morphine Group ◽  
Registration Number ◽  
To Receive ◽  
Registry Record ◽  
Infiltrating Endometriosis

Abstract Background The objective of this study was to compare the analgesic potency of oxycodone versus morphine after laparoscopic deep infiltrating endometriosis resection. Methods Fifty patients undergoing laparoscopic deep infiltrating endometriosis resection were randomized to receive oxycodone or morphine intravenous-PCA after surgery. The primary outcome was opioid consumption during the 24 h after surgery. Secondary outcomes included time to first request for analgesia, the number of bolus, pain, sedation, nausea, vomiting, respiratory depression, and bradycardia. The prominent pain that caused patients to press the analgesic device was also recorded. Results Oxycodone consumption (14.42 ± 2.83) was less than morphine consumption (20.14 ± 3.83). Compared with the morphine group, the total number of bolus (78 vs 123) was less and the average time to first request for analgesia (97.27 ± 59.79 vs 142.17 ± 51) was longer in the oxycodone group. The incidence of nausea was higher in the morphine group than in the oxycodone group at 0–2 h (45.45% vs 17.19%), 2–4 h (50% vs 17.19%),12–24 h (40.91% vs 13.04%) and 0–24 h (39.17% vs 19.13%). The overall incidence of vomiting was higher in the morphine group (27.27% vs 13.92%). There was no difference in visual analogue scale score, the incidence of respiratory depression, and bradycardia between groups. Of the three types of pain that prompted patients to request analgesia, the incidence of visceral pain was highest (59.9%, P < 0.01). Conclusion Oxycodone was more potent than morphine for analgesia after laparoscopic endometriosis resection, and oxycodone has fewer side effects than morphine. Name of the registry: Chinese Clinical Trial Registry Trial registration number: ChiCTR1900021870 URL of trial registry record:http://www.chictr.org.cn/edit.aspx?pid=35799&htm=4 Date of registration: 2019/3/13 0:00:00

Sign in / Sign up

Export Citation Format

Share Document