Early-onset epileptic encephalopathy with hearing loss in two siblings with TBC1D24 recessive mutations

Eur J Paediatr Neurol. 2015 Mar;19(2):251-6. doi: 10.1016/j.ejpn.2014.12.011. Epub 2014 Dec 20.


Background: Recent studies have shown that recessive mutations in the TBC1D24 gene cause a variety of epilepsy syndromes, DOORS syndrome and nonsyndromic deafness.

Methods/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.

Conclusion: 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.

Keywords: Deafness; Early-onset epileptic encephalopathy; Myoclonic seizures; TBC1D24 gene.

Publication types

  • Case Reports

MeSH terms

  • Brain Diseases / genetics*
  • Carrier Proteins / genetics*
  • Developmental Disabilities / complications
  • Developmental Disabilities / etiology
  • Electroencephalography
  • Epilepsies, Myoclonic / complications
  • Epilepsies, Myoclonic / etiology
  • Epilepsy / genetics*
  • Epilepsy, Tonic-Clonic / complications
  • Epilepsy, Tonic-Clonic / etiology
  • Fatal Outcome
  • Female
  • Frameshift Mutation / genetics
  • GTPase-Activating Proteins
  • Genes, Recessive / genetics
  • Hearing Loss, Sensorineural / etiology
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Membrane Proteins
  • Muscle Hypotonia / complications
  • Muscle Hypotonia / etiology
  • Mutation / genetics*
  • Mutation, Missense / genetics
  • Nerve Tissue Proteins
  • Siblings


  • Carrier Proteins
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • TBC1D24 protein, human