Table 1.

Synopsis of the most relevant genes associated with complex hyperkinetic movement disorders

Gene	Main associated phenotype	Gene product	Inheritance	Age of onset	Diagnostic clues
ADCY5	ADCY5-related chorea	Adenylate cyclase 5	AD/de novo	Infancy to childhood	Axial hypotonia and delayed milestones Diurnal and sleep-related MD exacerbations Dystonia and myoclonus prominent in some cases
PDE10A	PDE10A-related chorea	Phosphodiesterase 10A	De novo/AD/AR	Infancy to childhood	Delayed motor-language milestones and dysarthria in recessive cases MRI: symmetrical T2-hyperintense bilateral striatal lesions in cases with heterozygous de novo mutations
FOXG1	Congenital Rett disease	Forkhead Box G1	De novo	Infancy to early childhood	Severe ID, absent language, acquired microcephaly MRI: corpus callosum aplasia/hypoplasia, delayed myelination, simplified gyration
ARX	Early infantile epileptic encephalopathy-type 1; X-linked mental retardation	Aristaless-related homeobox protein	XL	Infancy	Ohtahara/West syndrome, severe mental retardation, generalized dystonia/dyskinesias with recurrent status dystonicus
STXBP1	Early infantile epileptic encephalopathy-type 4	Syntaxin-binding protein 1	De novo	Early infancy to childhood	Onset of seizures within one year of age. Developmental delay, ID, autistic-like features, ataxia with or without dyskinesias/dystonia
SYT1	Severe motor delay and intellectual disability	Synaptotagmin-1	De novo	Infancy	Severely delayed motor development without seizures
UNC13A	Congenital encephalopathy with dyskinesias	Unc-13 homolog A	De novo	Congenital	Developmental and speech delay; ID, congenital dyskinesias with intention tremor, rare febrile seizures
GNAO1	Early infantile epileptic encephalopathy type 17/Ohtahara syndrome	Gαo subunit of GPCR	De novo	Infancy to childhood	Developmental delay and ID Long-lasting MD exacerbations not related to sleep Epilepsy can be absent or well controlled
GRIN1	Mental retardation, autosomal dominant 8	GluN1 subunit of NMDAR	De novo/AR	Infancy	Severe developmental delay and ID Early-onset epileptic seizures Oculogyric crises Cortical blindness, dysmorphic traits, microcephaly
FRRS1L	Early infantile epileptic encephalopathy-type 37	Ferric Chelate Reductase 1-like	AR	Infancy	Psychomotor regression after normal development Severe encephalopathic epilepsy Choreo-athetosis in infancy/childhood, parkinsonism in adolescence
TBC1D24	Early infantile epileptic encephalopathy type 16	TBC1 domain family, member 24	AR	Infancy	Early-onset myoclonic seizures Variable degrees of ID Dystonia
GPR88	GPR88-related chorea	G protein-coupled receptor 88	AR	Infancy to childhood	Developmental and language delay Severe mental retardation Scarcely progressive chorea
KMT2B	DYT28 dystonia	lysine-specific histone methyltransferase 2B	De novo/AD	Childhood-adolescence	Onset in lower limbs and prominent oro-mandibular/laryngeal involvement Mild dysmorphic traits; mild ID Good and sustained response to pallidal DBS
ATP1A3	AHC RDP CAPOS syndrome	Na+/K+ ATPase, α3 subunit	De novo/AD	Infancy to fifth decade	Abrupt onset of neurological signs (dystonia, muscular weakness, ataxia) Initial hemisomatic distribution Identifiable triggering factors

MD, movement disorders; GPCR, guanine nucleotide-binding protein-coupled receptors; NMDAR, glutamatergic N-methyl-D-aspartate receptors; ID, intellectual disability; AHC, alternating hemiplegia of childhood; RDP, rapid-onset dystonia parkinsonism; CAPOS, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss; DBS, deep brain stimulation