Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy
PBN-AR
Instytucja
Instytut Matki i Dziecka
Źródłowe zdarzenia ewaluacyjne
Informacje podstawowe
Główny język publikacji
en
Czasopismo
JOURNAL OF MEDICAL GENETICS
ISSN
0022-2593
EISSN
1468-6244
Wydawca
B M J PUBLISHING GROUP
DOI
URL
Rok publikacji
2016
Numer zeszytu
8
Strony od-do
511-522
Numer tomu
53
Link do pełnego tekstu
Identyfikator DOI
Liczba arkuszy
Autorzy
Pozostali autorzy
+ 57
Słowa kluczowe
en
Epilepsy and seizures
Genetics
Neurology
SYNGAP1-associated intellectual disability
Streszczenia
Język
en
Treść
Objective We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype–phenotype correlations. Methods We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clinical data from patients with SYNGAP1 mutations from other centres were also collected, focusing on developmental aspects and the associated epilepsy phenotype. A review of SYNGAP1 mutations published in the literature was also performed. Results We describe 17 unrelated affected individuals carrying 13 different novel loss-of-function SYNGAP1 mutations. Developmental delay was the first manifestation of SYNGAP1-related encephalopathy; intellectual disability became progressively obvious and was associated with autistic behaviours in eight patients. Hypotonia and unstable gait were frequent associated neurological features. With the exception of one patient who experienced a single seizure, all patients had epilepsy, characterised by falls or head drops due to atonic or myoclonic seizures, (myoclonic) absences and/or eyelid myoclonia. Triggers of seizures were frequent (n=7). Seizures were pharmacoresistant in half of the patients. The severity of the epilepsy did not correlate with the presence of autistic features or with the severity of cognitive impairment. Mutations were distributed throughout the gene, but spared spliced 3′ and 5′ exons. Seizures in patients with mutations in exons 4–5 were more pharmacoresponsive than in patients with mutations in exons 8–15. Conclusions SYNGAP1 encephalopathy is characterised by early neurodevelopmental delay typically preceding the onset of a relatively recognisable epilepsy comprising generalised seizures (absences, myoclonic jerks) and frequent triggers.
Cechy publikacji
discipline:Medycyna
discipline:Medicine
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:746364
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