Table 2.3.

Dystonia associated with other neurogenetic disorders

Group	Disorder	MIM	Gene	Inheritance	Protein	Phenotype
Dominant ataxias	SCA1	164400	ATXN1	AD	Ataxin-1	Ataxia, slow saccades, dysarthria, corticospinal signs, dystonia
	SCA2	183090	ATXN2	AD	Ataxin-2	Ataxia, slow saccades, dysarthria, hyporeflexia, dystonia
	SCA3	109150	ATXN3	AD	Ataxin-3	Ataxia, ophthalmoplegia, parkinsonism, dystonia, spasticity, neuropathy
	SCA6	183086	CACNA1A	AD	α-1A subunit P/Q voltage-gated Ca²⁺ channel	Ataxia, nystagmus, dystonia
	SCA7	164500	ATXN7	AD	Ataxin-7	Ataxia, macular degeneration, dystonia, spasticity
	SCA8	608768	ATXN8	AD	Ataxin-8	Ataxia, nystagmus, spasticity, dystonia, sensory neuropathy
	SCA12	604326	PPP2R2B	AD	Serine/threonine-protein phosphatase 2A 55-kDa regulatory subunit B, β isoform	Ataxia, facial myokymia, action tremor, dystonia, parkinsonism, dementia
	SCA14	605361	PRKCG	AD	Protein kinase C, gamma	Ataxia, myoclonus, slow saccades, focal dystonia
	SCA17	607136	TBP	AD	TATA box-binding protein	Ataxia, spasticity, seizures, dystonia, dementia
	Dentatorubral- pallidoluysian atrophy (DRPLA)	125370	ATN1	AD	Atrophin 1	Ataxia, myoclonus, seizures, dystonia
Recessive ataxias	Friedreich ataxia	606829	FXN	AR	Frataxin	Ataxia, nystagmus, optic atrophy, cardiomyopathy, sensory neuropathy, spasticity, dystonia, diabetes, scoliosis, pes cavus
	Ataxia telangiectasia	208900	AT	AR	Serine-protein kinase ATM	Ataxia, telangiectasis, oculomotor apraxia, immune deficiency, seizures, dystonia
	Ataxia with oculomotor apraxia type 1	208920	APTX	AR	Aprataxin	Ataxia, oculomotor apraxia, scoliosis, pes cavus, dystonia, choreoathetosis, neuropathy
	Ataxia with oculomotor apraxia type 2	606002	SETX	AR	Senataxin	Ataxia, oculomotor apraxia, nystagmus, amyotrophy, dystonia, chorea, neuropathy
	Ataxia with selective vitamin E deficiency	277460	TTPA	AR	α-Tocopherol transfer protein	Ataxia, areflexia, loss of proprioception, dystonia, xanthelasma, tendon xanthomas
X-linked ataxias	Mental retardation, X-linked syndromic, Christianson type	300243	SLC9A6	X-linked dominant	Sodium/hydrogen exchanger 6	Ataxia, spasticity, mental retardation, dysmorphic features, microcephaly, dystonia, autistic
Dopamine metabolism	AADC deficiency	608643	AADC	AR	Aromatic L-amino acid decarboxylase	Psychomotor delay, ptosis, oculogyric crises, dystonia, truncal hypotonia, temperature instability, hypotension
Dopamine metabolism	Infantile parkinsonism–dystonia	613135	SLC6A3	AR	Presynaptic dopamine transporter	Parkinsonism, dystonia, developmental delay, upper motor neuron signs
Deafness	Mohr–Tranebjaerg syndrome	300356	TIMM8A	X-linked	Translocase of inner mitochondrial membrane 8	Sensorineural deafness at an early age followed by varying degrees of dystonia along with visual and cognitive disability
Deafness	Woodhouse–Sakati syndrome	241080	DCAF17	AR	Nucleolar protein	Sensorineural deafness, seizures, sensory neuropathy, mental retardation, alopecia, hypogonadism, diabetes mellitus
Spasticity	Spastic paraplegia 35 (SPG35)	612319	FA2H	AR	Fatty acid 2-hydroxylase	Spasticity, cognitive decline, dystonia, optic atrophy, brain iron accumulation, leukodystrophy
	SPG2, Pelizaeus– Merzbacher disease	312920, 312080	PLP1	X-linked	Proteolipid protein-1	Spasticity, ataxia, dystonia, developmental delay, hypomyelinative leukodystrophy
	SPG15	ZFYVE26	KI	AR	Spastizin	Spasticity, amyotrophy, ataxia, mental retardation, dystonia
Metabolic and storage	Wilson disease	277900	ATP7B	AR	ATPase, Cu²⁺ transporting β polypeptide	Hepatitis, liver failure, Kayser–Fleischer rings, tremor, dystonia, personality changes
	Lesch–Nyhan syndrome	300322	HPRT1	X-linked recessive	Hypoxanthine guanine phosphoribosyl-transferase I	Hyperuricemia, gout, nephrolithiasis, self-injurious behavior, dystonia, mental retardation, athetosis
	Glutaric academia I	231670	GCDH	AR	Glutaryl-CoA dehydrogenase	Macrocephaly, hepatomegaly, dystonia, choreoathetosis, infantile encephalopathy, striatal necrosis
	Pyruvate dehydrogenase deficiency	312170	PDHA1	X-linked dominant	Pyruvate dehydrogenase E1-α deficiency	Low birth weight, microcephaly, dysmorphic features, psychomotor retardation, seizures, choreoathetosis, dystonia, ataxia, lactic acidosis
	Homocystinuria	236200	CBS	AR	Cystathionine β-synthase deficiency	Tall stature, ectopic lentis, skeletal abnormalities, seizures, mental retardation, dystonia, thromboembolism
	Biotin-responsive basal ganglia disease	607483		AR		Subacute encephalopathy, dysphagia, dysarthria, dystonia, nystagmus, seizures
	Niemann–Pick type C1	257220	NPC1	AR	Neimann-Pick C1 protein	Hepatosplenomegaly, supranuclear gaze palsy, dementia, dysarthria, dystonia, ataxia
	Niemann–Pick type C2	607625	NPC2	AR	Epididymal secretory protein E1	Hepatosplenomegaly, respiratory failure, supranuclear gaze play, dementia, dysarthria, dystonia, ataxia
	GM1 gangliosidosis	230500	GLB1	AR	β-Galactosidase	Dysmorphic face/neck, dwarfism, macular cherry-red spot, hepatosplenomegaly, mental retardation, dystonia
	GM2 gangliosidosis	272750	GM2A	AR	Ganglioside GM2 activator	Macular cherry-red spot, blindness, psychomotor delay, dementia, seizures, dystonia
	Tay–Sachs disease	272800	HEXA	AR	β-Hexosaminidase, subunit α	Macular cherry-red spot, blindness, psychomotor deterioration, seizures, dementia, dystonia
	Neuronal ceroid-lipofuscinosis^a	204200	CLN3	AR	Battenin	Retinitis pigmentosa with progressive vision loss, psychomotor degeneration with dementia, parkinsonism, ataxia, dystonia, seizures
	Metachromatic leukodystrophy	250100	ARSA	AR	Arylsulfatase A	Optic atrophy, dementia, ataxia, chorea, dystonia, seizures, demyelinating polyneuropathy
Mitochondrial	Leber hereditary optic atrophy (LHON)	53500	MTND1^b	M	NADH dehydrogenase I	Optic atrophy, action tremor, dystonia, peripheral neuropathy
Mitochondrial	Leigh syndrome^c	25600	MTND2	AR, M, X-linked	NAD dehydrogenase subunit 2	Ophthalmoplegia, pigmentary retinopathy, psychomotor retardation, ataxia, dystonia, spasticity, seizures, lactic acidosis
Other neuro- degenerative disorders	Rett syndrome	312750	MECP2	X-linked dominant	MECP2	Mental retardation, stereotypies, parkinsonism, dystonia
	Huntington disease (HD)	143100	HTT	AD	Huntington	Chorea, personality changes, dementia, dystonia
	Huntington disease-like 2 (HDL2)	606438	JPH3	AD	Junctophilin 3	Dementia, akinetic-rigid syndrome, mild chorea, mild dystonia
	Choreoacanthocytosis	200150	VPS13A	AR	Chorein	Orofacial dyskinesias, dysphagia, choreoathetosis, dystonia, seizures, parkinsonism, acanthocytosis
	Creutzfeldt–Jakob disease, familial	123400	PRNP	AD	Prion protein	Dementia, delirium, myoclonus, akinetic-rigid syndrome, dystonia, ataxia

AD, autosomal dominant; AR, autosomal recessive; M, mitochondrial.

Neuronal ceroid lipofuscinoses are a group of genetically heterogeneous disorders characterized by intracellular accumulation of autofluorescent lipopigment and include dementia, movement disorders, vision loss, and seizures as phenotypic features (Getty and Pearce, 2011).

LHON has been associated with variants in ND1, ND2, ND4, ND4L, ND5, ND6, MTCYB, MTCO1, and MTAP6 (Toñska et al., 2010).

Leigh syndrome is associated with marked genetic hetereogeneity and can be caused by mutations in either mtDNA or nDNA (Finsterer, 2008).