Klinische FragestellungBewegungsstörungen, Beginn im Erwachsenenalter; DD

NGS +

Bewegungsstörungen umfassen eine lange Reihe heterogener neurologischer Syndrome, die die Fähigkeit zur Erzeugung und Kontrolle von Bewegungen aufgrund von Funktionsstörungen in den Basalganglien und/oder den damit verbundenen Strukturen beeinträchtigen. Bewegungsstörungen können erworben sein oder als Folge zahlreicher Erbkrankheiten auftreten, wobei sich auch letztere durch eine große klinische und genetische Heterogenität und häufig durch klinische Überlappungen auszeichnen, was oftmals mehrdeutige Genotyp-Phänotyp-Korrelationen hervorruft. Die schwierige klinische Diagnostik ist daher mitunter keine wirklich solide Basis für gezielte Mutationsanalysen. Unsere genetische Diagnose-Strategie mittels Hochdurchsatz-Sequenzier-Technologie umfasst knapp 100 Gene, die an Bewegungsstörungen beteiligt sind. Die Mutationshäufigkeiten variieren in den verschiedenen Krankheitskategorien, und die phänotypischen Spektren sind recht breit und überschneiden sich. Da auch die Genotyp-Phänotyp-Korrelationen im Großen und Ganzen unterschiedlich sind, hängt die diagnostische Ausbeute stark vom individuellen Befund des Patienten ab, liegt aber durchschnittlich bei über 25%. Daher schließt andererseits aber ein negatives DNA-Testergebnis die klinische Diagnose nicht aus.

• 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)