ClinVar

In 2 unrelated families, 1 Canadian and 2 Belgian, with developmental and epileptic encephalopathy (DEE1; 308350), described as infantile spasm syndrome, Stromme et al. (2002) found that 8 and 2 male affected members, respectively, had an additional stretch of 7 tandem GCG repeats within the normal stretch of 10 GCG triplet repeats in exon 2. These families had been described by Bruyere et al. (1999) and Claes et al. (1997). The effect of the mutation on the protein product was polyalanine expansion. The haplotype background of the mutation was different in the 2 families, indicating that a recurrent mutation had occurred. The normal tract of 16 alanine residues (amino acids 100-115) was expanded to 23.

Shoubridge et al. (2007) showed that this polyalanine expansion mutation was associated with an increased propensity of ARX protein aggregation and a shift from nuclear to cytoplasmic localization.

Guerrini et al. (2007) identified the (GCG)10+7 expansion in 6 boys, including 2 pairs of brothers, with a severe form of DEE1, which they termed infantile epileptic-dyskinetic encephalopathy, including chorea and dystonia. All 6 boys also had severe mental retardation. Seizure onset occurred between 2 and 5 months of age and earlier than dystonia, which was severe and progressed to quadriplegic dyskinesia. Three children had recurrent, life-threatening status dystonicus. Brain MRI showed basal ganglia abnormalities in 4 patients.