Cooccurrence of Two Different Genetic Diseases: A Case of Valproic Acid Hepatotoxicity in Nicolaides-Baraitser Syndrome (SMARCA2 Mutation)-Due to a POLG1-Related Effect?

Neuropediatrics. 2020 Feb;51(1):49-52. doi: 10.1055/s-0039-1694976. Epub 2019 Sep 21.


Nicolaides-Baraitser syndrome (NCBRS) is a rare disease caused by a mutation in the SMARCA2 gene. Clinical features include craniofacial dysmorphia and abnormalities of the limbs, as well as intellectual disorder and often epilepsy. Hepatotoxicity is a rare complication of the therapy with valproic acid (VPA) and a mutation of the polymerase γ (POLG) might lead to a higher sensitivity for liver hepatotoxicity. We present a patient with the coincidence of two rare diseases, the NCBRS and additionally a POLG1 mutation in combination with a liver hepatotoxicity. The co-occurrence in children for two different genetic diseases is discussed with the help of literature review.

Publication types

  • Case Reports

MeSH terms

  • Anticonvulsants / adverse effects*
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / genetics
  • Child
  • DNA Polymerase gamma / genetics*
  • Facies*
  • Female
  • Foot Deformities, Congenital* / drug therapy
  • Foot Deformities, Congenital* / genetics
  • Humans
  • Hypotrichosis* / drug therapy
  • Hypotrichosis* / genetics
  • Intellectual Disability* / drug therapy
  • Intellectual Disability* / genetics
  • Transcription Factors / genetics*
  • Valproic Acid / adverse effects*


  • Anticonvulsants
  • SMARCA2 protein, human
  • Transcription Factors
  • Valproic Acid
  • DNA Polymerase gamma
  • POLG protein, human

Supplementary concepts

  • Nicolaides Baraitser syndrome