title: The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations.
abstract: OBJECTIVE
  The coincidence of autism with epilepsy is 27% in those individuals with intellectual disability.1Individuals with loss-of-function mutations in SHANK3 have intellectual disability, autism, and variably, epilepsy.2-5The spectrum of seizure semiologies and electroencephalography (EEG) abnormalities has never been investigated in detail. With the recent report that SHANK3 mutations are present in approximately 2% of individuals with moderate to severe intellectual disabilities and 1% of individuals with autism, determining the spectrum of seizure semiologies and electrographic abnormalities will be critical for medical practitioners to appropriately counsel the families of patients with SHANK3 mutations.
  
  
  METHODS
  A retrospective chart review was performed of all individuals treated at the Blue Bird Circle Clinic for Child Neurology who have been identified as having either a chromosome 22q13 microdeletion encompassing SHANK3 or a loss-of-function mutation in SHANK3 identified through whole-exome sequencing. For each subject, the presence or absence of seizures, seizure semiology, frequency, age of onset, and efficacy of therapy were determined. Electroencephalography studies were reviewed by a board certified neurophysiologist. Neuroimaging was reviewed by both a board certified pediatric neuroradiologist and child neurologist.
  
  
  RESULTS
  There is a wide spectrum of seizure semiologies, frequencies, and severity in individuals with SHANK3 mutations. There are no specific EEG abnormalities found in our cohort, and EEG abnormalities were present in individuals diagnosed with epilepsy and those without history of a clinical seizure.
  
  
  CONCLUSIONS
  All individuals with a mutation in SHANK3 should be evaluated for epilepsy due to the high prevalence of seizures in this population. The most common semiology is atypical absence seizure, which can be challenging to identify due to comorbid intellectual disability in individuals with SHANK3 mutations; however, no consistent seizure semiology, neuroimaging findings, or EEG findings were present in the majority of individuals with SHANK3 mutations.
authors.affiliation: Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, U.S.A.. holder@bcm.edu.
authors.forename: J Lloyd
authors.initials: JL
authors.lastname: Holder
authors.affiliation: Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, U.S.A.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Quach
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use; D058256:Brain Waves / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004569:Electroencephalography; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human
keywords: 
  SHANK3
  ; Autism; Electroencephalography; Epilepsy; Phelan-McDermid syndrome