IllnessMovement disorders, adult onset; differential diagnosis

NGS +

Movement disorders encompass a large series of heterogeneous neurological syndromes that affect the ability to generate and control movement due to dysfunction in the basal ganglia and/or associated structures. Movement disorders may be acquired or occur as a consequence of numerous inherited disorders. The latter are characterized by a great deal of clinical and genetic heterogeneity and by clinical overlaps, often resulting in ambiguous genotype-phenotype correlations. Thus, the demanding clinical diagnosis appears sometimes not as a truly solid basis for targeted mutation analyses. Our diagnostic genetic strategy using high-throughput sequencing technology includes nearly 100 different genes involved in movement disorders. Mutation frequencies vary across disease categories, and phenotypic spectra are quite broad and overlapping. Because genotype-phenotype correlations also vary broadly, the diagnostic yield depends heavily on the individual patient's findings, but averages over 25%. Therefore, on the other hand, a negative DNA test result does not exclude the clinical diagnosis.

• DD: Dystonie, Chorea, Parkinson, Basalganglien-, Kanal- oder verwandte Erkrankungen
• Allelic: Aphasia, primary progressive (GRN)
• Allelic: Arthrogryposis multiplex congenita 5 (TOR1A)
• Allelic: Breast cancer, susceptibility to (ATM)
• Allelic: CAPOS syndrome (ATP1A3)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2X (SPG11)
• Allelic: Congenital hypotonia, epilepsy, developmental delay + digital anomalies (ATN1)
• Allelic: Dementia, Lewy body (SNCA)
• Allelic: Dermatofibrosarcoma protuberans (PDGFB)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Allelic: Fetal akinesia, resp. insuff., microcephaly, polymicrogyria + dysmorphic face (ATP1A2)
• Allelic: Gaucher disease, perinatal lethal (GBA)
• Allelic: Intellectual developmental disorder, XL 29 (ARX)
• Allelic: Intellectual developmental disorder, XL 72 (RAB39B)
• Allelic: Intellectual developmental disorder, XL syndromic 33 (TAF1)
• Allelic: Kufor-Rakeb syndrome (ATP13A2)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: Meningioma, SIS-related (PDGFB)
• Allelic: Optic atrophy 12 (AFG3L2)
• Allelic: Seizures, benign familial infantile, 2 (PRRT2)
• Allelic: Spastic paraplegia 43, AR (C19orf2)
• Allelic: Thyroid cancer, nonmedullary, 1 (NKX2-1)
• 3-methylglutaconic aciduria, type I (AUH)
• Alexander disease (GFAP)
• Alternating hemiplegia of childhood 1 (ATP1A2)
• Alternating hemiplegia of childhood 2 (ATP1A3)
• Amyotrophic lateral sclerosis 5, juvenile (SPG11)
• Amyotrophic lateral sclerosis, susceptibility to (DCTN1)
• Amyotrophic lateral sclerosis, susceptibility to, 13 (ATXN2_CAG)
• Aromatic L-amino acid decarboxylase deficiency (DDC)
• Ataxia, early-onset, with oculomotor apraxia + hypoalbuminemia (APTX)
• Ataxia-telangiectasia (ATM)
• Baraitser-Winter syndrome 1 (ACTB)
• Basal ganglia calcification, idiopathic, 1 (SLC20A2)
• Basal ganglia calcification, idiopathic, 5 (PDGFB)
• Basal ganglia calcification, idiopathic, 6 (XPR1)
• Basal ganglia calcification, idiopathic, 7, AR (MYORG syn. KIAA1161)
• Brain abnormalities, neurodegeneration, and dysosteosclerosis (CSF1R)
• Cerebellar ataxia (CP)
• Cerebellar ataxia + hypogonadotropic hypogonadism (RNF216)
• Cerebral amyloid angiopathy, PRNP-related (PRNP)
• Cerebrotendinous xanthomatosis (CYP27A1)
• Ceroid lipofuscinosis, neuronal, 11 (GRN)
• Chediak-Higashi syndrome (LYST)
• Chorea, hereditary benign (NKX2-1)
• Choreoacanthocytosis (VPS13A)
• Choreoathetosis, hypothyroidism + neonatal respiratory distress (NKX2-1)
• Congenital hypotonia, epilepsy, developmental delay + digital anomalies (ATN1)
• Creutzfeldt-Jakob disease (PRNP)
• Dementia, frontotemporal, with/-out parkinsonism (MAPT)
• Dentatorubral-pallidoluysian atrophy (ATN1)
• Dentatorubral-pallidoluysian atrophy (ATN1_CAG)
• Developmental + epileptic encephalopathy 1 (ARX)
• Developmental + epileptic encephalopathy 42 (CACNA1A)
• Developmental + epileptic encephalopathy 53 (SYNJ1)
• Developmental + epileptic encephalopathy 98 (ATP1A2)
• Developmental + epileptic encephalopathy 99 (ATP1A3)
• Dyskinesia, limb + orofacial, infantile-onset (PDE10A)
• Dystonia 16 (PRKRA)
• Dystonia 2, torsion, AR (HPCA)
• Dystonia 23 [panelapp, MONDO:0013928] (CIZ1)
• Dystonia 24 (ANO3)
• Dystonia 25 (GNAL)
• Dystonia 28, childhood-onset (KMT2B)
• Dystonia 30 (VPS16)
• Dystonia 4, torsion, AD (TUBB4A)
• Dystonia 6, torsion (THAP1)
• Dystonia 9 (SLC2A1)
• Dystonia, DOPA-responsive, with/-out hyperphenylalaninemia (GCH1)
• Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (SPR)
• Dystonia, juvenile-onset (ACTTB)
• Dystonia-1, torsion (TOR1A)
• Dystonia-11, myoclonic (SGCE)
• Dystonia-12 (ATP1A3)
• Dystonia-Parkinsonism, XL (TAF1)
• Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8 (TBK1)
• Epilepsy, progressive myoclonic 1A, Unverricht + Lundborg (CSTB_CCCCGCCCCGCG)
• Episodic ataxia, type 2 (CACNA1A)
• Episodic ataxia, type 2 (CACNA1A_CAG)
• Episodic kinesigenic dyskinesia 1 (PRRT2)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (C9orf72_GGGGCC)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (TBK1)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (CHMP2B)
• Frontotemporal lobar degeneration with ubiquitin-positive inclusions (GRN)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• GM1-gangliosidosis, type I, II, III (GLB1)
• Gabriele-de Vries syndrome (YY1)
• Gaucher disease, type I, II, III; IIIC (GBA)
• Gerstmann-Straussler disease (PRNP)
• HARP syndrome: Hypoprebetalipoproteinemia, Acanthocytosis, Rp, Pallidal degen. (PANK2)
• Hemosiderosis, systemic, due to aceruloplasminemia (CP)
• Huntington disease-like 1 (PRNP)
• Huntington disease-like 2 (JPH3_CAG)
• Hydranencephaly with abnormal genitalia (ARX)
• Hyperferritinemia-cataract syndrome (FTL)
• Hypermanganesemia with dystonia 1 (SLC30A10)
• Hyperphenylalaninemia, BH4-deficient, A (PTS)
• Hyperphenylalaninemia, BH4-deficient, B (GCH1)
• Hyperphenylalaninemia, BH4-deficient, C (QDPR)
• Hypoceruloplasminemia, hereditary (CP)
• Infantile neuroaxonal dystrophy 1 (PLA2G6)
• Insomnia, fatal familial (PRNP)
• Intellectual developmental disorder with paroxysmal dyskinesia or seizures (PDE2A)
• Jaberi-Elahi syndrome (GTPBP2)
• Kuru, susceptibility to (PRNP)
• L-ferritin deficiency, AD + AR (FTL)
• Leukodystrophy, hypomyelinating, 6 (TUBB4A)
• Leukoencephalopathy, diffuse hereditary, with spheroids (CSF1R)
• Lissencephaly, XL 2 (ARX)
• Machado-Joseph disease (ATXN3_CAG)
• Mental retardation, AD 35 (PP2R5D)
• Metachromatic leukodystrophy (ARSA)
• Migraine, familial basilar (ATP1A2)
• Migraine, familial hemiplegic, 1 (CACNA1A)
• Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Migraine, familial hemiplegic, 2 (ATP1A2)
• Mohr-Tranebjaerg syndrome (TIMM8A)
• Mucopolysaccharidosis type IVB, Morquio (GLB1)
• Neurodegeneration with brain iron accumulation 1 (PANK2)
• Neurodegeneration with brain iron accumulation 2B (PLA2G6)
• Neurodegeneration with brain iron accumulation 3 (FTL)
• Neurodegeneration with brain iron accumulation 4 (C19orf2)
• Neurodegeneration with brain iron accumulation 5 (WDR45)
• Neurodevelopm. disorder, hypotonia + autistic features with/-out hyperkinetic movements (VAMP2)
• Neurodevelopmental disorder, hypotonia + autistic features with/-out hyperkinetic movements (VAMP2)
• Neuronopathy, distal hereditary motor, type VIIB (DCTN1)
• Parkinson disease 1 (SNCA)
• Parkinson disease 14, AR (PLA2G6)
• Parkinson disease 15, AR (FBXO7)
• Parkinson disease 17 (VPS35)
• Parkinson disease 18 (EIF4G1)
• Parkinson disease 19a, juvenile-onset (DNAJC6)
• Parkinson disease 19b, early-onset (DNAJC6)
• Parkinson disease 20, early-onset (SYNJ1)
• Parkinson disease 22, AD (CHCHD2)
• Parkinson disease 4 (SNCA)
• Parkinson disease 5, susceptibility to (ICHL1)
• Parkinson disease 6, early onset (PINK1)
• Parkinson disease 7, AR early-onset (PARK7)
• Parkinson disease 8 (LRRK2)
• Parkinson disease, juvenile, type 2 (PRKN)
• Parkinson disease, late-onset, susceptibility to (ATXN2)
• Parkinson disease, late-onset, susceptibility to (GBA)
• Parkinson disease, susceptibility to (MAPT)
• Parkinson disease, susceptibility to (TBP_CAG)
• Paroxysmal nonkinesigenic dyskinesia 1 (PNKD)
• Partington syndrome (ARX)
• Pelizaeus-Merzbacher disease (PLP1)
• Perry syndrome (DCTN1)
• Pick disease (MAPT)
• Proud syndrome (ARX)
• Rett syndrome, congenital variant (FOXG1)
• Seizures, benign familial infantile, 2 (PRRT2)
• Spastic ataxia 5, AR (AFG3L2)
• Spastic paraplegia 11, AR (SPG11)
• Spastic paraplegia 2, XL (PLP1)
• Spastic paraplegia 78, AR (ATP13A2)
• Spastic paraplegia 79, AR (UCHL1)
• Spinocerebellar ataxia 1 (ATXN1_CAG)
• Spinocerebellar ataxia 12 (PPP2R2B_CAG)
• Spinocerebellar ataxia 17 (TBP_CAG)
• Spinocerebellar ataxia 2 (ATXN2_CAG)
• Spinocerebellar ataxia 28 (AFG3L2)
• Spinocerebellar ataxia 6 (CACNA1A)
• Spinocerebellar ataxia 6 (CACNA1A_CAG)
• Spinocerebellar ataxia, AR 29 (VPS41)
• Spongiform encephalopathy with neuropsychiatric features (PRNP)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Striatal degeneration, AD (PDE10A)
• Supranuclear palsy, progressive (MAPT)
• Supranuclear palsy, progressive atypical (MAPT)
• Thiamine metabolism dysfunction syndr. 2 (biotin-/thiamine-resp. encephalopathy type 2 (SLC19A3)
• Waisman syndrome (RAB39B)
• Wilson disease (ATP7B)
• Woodhouse-Sakati syndrome (DCAF17)