Table 1.

Overview of molecular, genetic, and clinical features of postsynaptic movement disorders related to defects in the cAMP pathway in striatal medium spiny neurons

Gene	Protein	Postulated effect of mutation on protein function	Inheritance	Typical age of onset	Typical clinical features	Distinguishing clinical features	Drugs reported to have some efficacy
ADCY5	Adenylate cyclase 5	Gain of function	AD (familial, de novo, and somatic mosaicism)	Infancy to childhood	Generalized chorea, perioral dyskinesia, dystonia and myoclonus, lower limb spasticity, static or mildly progressive	Fluctuation in severity and frequency of MD, sleep-related episodes of hyperkinesia	Clonazepam, clobazam, acetazolamide, DBS
PDE10A	Phosphodiesterase 10A	Loss of function	AD (de novo) AR (biallelic, inheriting one disease allele from each parent)	Infancy to childhood	Generalized chorea, orolingual dyskinesia, static or mildly progressive	Abnormal MRI in heterozygous patients with bilateral T2-hyperintense striatal lesions	na
GNAO1	Gαo subunit of GPCR	Loss of function (EE phenotype) Gain of function (MD phenotype)	AD (de novo, somatic, and gonadal somaticism)	Infancy to childhood	Spectrum includes EE phenotype: neonatal-/infantile-onset seizures, infantile spasms, dyskinesia MD phenotype: Generalized chorea, facial and orolingual dyskinesia, dystonia, progressive	Severe exacerbations of chorea/ballism with autonomic dysfunction, complex motor stereotypies	Tetrabenazine and neuroleptics, topiramate, DBS especially for hyperkinetic exacerbations
GNAL1	Gαolf subunit of GPCR	Loss of function	AD (familial, de novo) AR	Infancy (AR) Adulthood (AD)	Generalized chorea, hypertonia Progressive dystonia	na	na
GPR88	G-protein coupled receptor 88	Loss of function	AR	Childhood	Generalized chorea	na	na

AD, autosomal dominant; AR, autosomal recessive; DBS, deep brain stimulation; EE, epileptic encephalopathy; MD, movement disorder; na, not available