Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability.

BACKGROUND Mutations of theADCY5 have been identified in patients with familial dyskinesia, early-onsetautosomal dominant chorea and dystonia, and benign hereditary chorea. Most ofthe ADCY5 mutations are de novo or transmitted in an autosomal dominantfashion. Only two pedigrees are known to show autosomal recessive inheritance. OBJECTIVES We report twosiblings with severe ID, dystonic movement, and growth failure with unknownetiology. METHODS We planned a proband-parentapproach using whole exome sequencing. RESULTS Homozygous mutationin exon 21 of the ADCY5 (p.R1238W) was identified in the siblings. Althoughtheir parents were heterozygous for the mutation, they were free from clinicalmanifestations. CONCLUSIONS Our results furtherexpand the phenotype/genotype correlations of the ADCY5-related disorders.Mutations of ADCY5 should be considered in pediatric patients with ID andinvoluntary movement.