title: Early-onset epileptic encephalopathy with hearing loss in two siblings with TBC1D24 recessive mutations.
abstract: BACKGROUND
  Recent studies have shown that recessive mutations in the TBC1D24 gene cause a variety of epilepsy syndromes, DOORS syndrome and nonsyndromic deafness.
  
  
  RESULTS
  We report on two siblings with hypotonia, early-onset epileptic encephalopathy, and severe developmental delay. The patients presented with clonic and myoclonic jerks within 1 h after birth. The seizures were resistant to treatment. Audiologic examination showed bilateral sensorineural hearing loss in both siblings. Genetic analysis revealed compound heterozygous mutations in the TBC1D24 gene: a novel missense mutation c.32A > G (p.Asp11Gly) in exon 2 and a frameshift mutation c.1008delT (p.His336Glnfs*12) in exon 4.
  
  
  CONCLUSIONS
  This report supports previous observations that mutations in TBC1D24 cause diverse phenotypes. In fact, early-onset epileptic encephalopathy with sensorineural hearing loss is an additional phenotype observed in patients with recessive TBC1D24 mutations.
authors.affiliation: Department of Child, Adolescent & Developmental Neurology, University Children's Hospital, Ljubljana, Slovenia.
authors.forename: Barbara Gnidovec
authors.initials: BG
authors.lastname: Stražišar
authors.affiliation: Department of Child, Adolescent & Developmental Neurology, University Children's Hospital, Ljubljana, Slovenia.
authors.forename: David
authors.initials: D
authors.lastname: Neubauer
authors.affiliation: Department of Neonatology, University Children's Hospital, Ljubljana, Slovenia.
authors.forename: Darja
authors.initials: D
authors.lastname: Paro Panjan
authors.affiliation: Institute of Medical Genetics, University Medical Centre, Ljubljana, Slovenia. Electronic address: karinwritzl@gmail.com.
authors.forename: Karin
authors.initials: K
authors.lastname: Writzl
mesh_terms: D001927:Brain Diseases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002658:Developmental Disabilities / Q000150:complications / Q000209:etiology; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000209:etiology; D004827:Epilepsy / Q000235:genetics*; D004830:Epilepsy, Tonic-Clonic / Q000150:complications / Q000209:etiology; D017809:Fatal Outcome; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D020690:GTPase-Activating Proteins; D005808:Genes, Recessive / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins; D009123:Muscle Hypotonia / Q000150:complications / Q000209:etiology; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009419:Nerve Tissue Proteins; D035781:Siblings
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C552551:TBC1D24 protein, human
keywords: Deafness; Early-onset epileptic encephalopathy; Myoclonic seizures; TBC1D24 gene