The role of ARX gene in a syndrome of infantile spasms with generalized dystonia was investigated in 6 boys from 4 families at the University of Florence, Italy, and other centers in Italy, Japan, and USA. Mutation analysis in 115 boys with cryptogenic infantile spasms found an expansion of the first PolyA tract of ARX in 6 (5.2%) ages 2 to 14, from four families, including two pairs of brothers. All six had mental retardation and generalized dystonia that developed at 6 months and progressed to quadriplegic dyskinesia within 2 years. Three had recurrent status dystonicus. Multifocal small cavities in the putamina were seen on the MRI of 4 children. ARX gene testing is recommended in boys with infantile spasms and unexplained dyskinetic quadriplegia. 
COMMENT. Several brain malformations are associated with mutations of the ARX gene, including X-linked lissencephaly with abnormal genitalia, hydrocephalus, and agenesis of the corpus callosum with abnormal genitalia (Proud syndrome). Syndromes associated with the same gene and without brain malformations include X-linked infantile spasms, Partington syndrome (mental retardation with mild dystonia), and X-linked mental retardation. The authors describe an “infantile epileptic-dyskinetic encephalopathy” in males with expansion of the first PolyA tract of ARX, and consisting of severe mental retardation, early-onset infantile spasms, and severe progressive generalized dystonia with status dystonicus, some patients showing basal ganglia cysts.