Novel <i>SYNGAP1</i> variant in a patient with intellectual disability and distinctive dysmorphisms

Kimura, Yuichi; Akahira-Azuma, Moe; Harada, Noriaki; Enomoto, Yumi; Tsurusaki, Yoshinori; Kurosawa, Kenji

doi:10.1111/cga.12273

Cited by 11 publications

(8 citation statements)

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“…Previous studies have reported individuals with SYNGAP1 deleterious variants and associated phenotypes. Reported phenotypic traits have included nearly universal epilepsy and intellectual disability/developmental delay, as well as variable presence of autism spectrum disorder and physical dysmorphisms [16, 17]. However, in-depth and longitudinal clinical characterization of a cohort of individuals ascertained for pathologic SYNGAP1 variants has not been undertaken.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression

Jiménez-Gómez

Niu

Andujar-Perez

et al. 2019

J Neurodevelop Disord

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Background The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression. Methods A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging, and serial neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed. Results Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28–174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism spectrum disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other neurophysiology-development associations or correlations were identified. Conclusions A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1 . An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker. Electronic supplementary material The online version of this article (10.1186/s11689-019-9276-y) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression

Jiménez-Gómez

Niu

Andujar-Perez

et al. 2019

J Neurodevelop Disord

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“…SYNGAP1 heterozygosity impairs sensory processing by reducing touch-related activity in the somatosensory cortex (13). Distinctive dysmorphism is observed in the SYNGAP1 mutation (14). The possible mechanism in epilepsy due to SYNGAP1 mutation is the increase in neuronal excitability caused by AMPAR activity (15).…”

Section: Discussionmentioning

confidence: 99%

SYNGAP1 mutation in a pediatric patient with autism spectrum disorder and intellectual disability

Çetin¹

2020

Dusunen Adam

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Autism spectrum disorder (ASD) is a disease characterized by interaction and communication deficiencies. Patients diagnosed with intellectual disability (ID) exhibit deficiencies in at least two behaviors associated with adaptation skills. The high level of association between neurodevelopmental diseases, especially ID, and ASD clearly reveals the presence of etiopathogenesis with an underlying multi-factorial and possibly a common genetic background. The SYNGAP1 gene has been associated with both ASD and non-syndromic ID. We report the case of a 13-year-old adolescent with SYNGAP1 gene mutation diagnosed with ASD, moderate ID, and epilepsy. The motor development of the patient, who had started walking at the age of 4, was delayed, and his language development was evidently inadequate since he still had no word. Stereotypical behaviors were observed with insufficient social interaction. As a result of the genetic analysis, the patient was determined to be heterozygous for a single nucleotide change (C>T) resulting in a false sense of mutation at position c.3134 in exon 15 of the SYNGAP1 gene. Thus, the present study aimed to contribute to the knowledge base on patients with rare SYNGAP1 mutation that plays a role in the etiological background of ASD, ID, and epilepsy comorbidity. To the best of our knowledge, this variant has not been reported in the scientific literature to date.

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“…Genetic analysis utilized the TruSight One Sequencing Panel kit with the MiSeq platform (Illumina, Inc., San Diego, California). Exome data alignment, variant calling, and variant annotation were assessed 3 . Copy number variants (CNVs) were calculated from log‐ratio analysis of exon depth 4 …”

Section: Figurementioning

confidence: 99%

Multiple craniosynostosis and facial dysmorphisms with homozygous IL11RA variant caused by maternal uniparental isodisomy of chromosome 9

Nishimura

Murakami

Hayashi

et al. 2020

Congenital Anomalies

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Novel SYNGAP1 variant in a patient with intellectual disability and distinctive dysmorphisms

Cited by 11 publications

References 10 publications

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression

SYNGAP1 mutation in a pediatric patient with autism spectrum disorder and intellectual disability

Multiple craniosynostosis and facial dysmorphisms with homozygous IL11RA variant caused by maternal uniparental isodisomy of chromosome 9

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