Klinische FragestellungParkinson-Syndrom + -Krankheit, Differentialdiagnose

NGS + X

[Sanger]

Parkinson Syndrom ist ein Oberbegriff mit verschiedenen Ätiologien (idiopathisches, nicht-idiopathisches Parkinson Syndrom). Die Parkinson Syndrome sind definiert durch Akinese und eines der unterschiedlich ausgeprägten Kardinalsymptome Rigor, Ruhetremor, posturale Instabilität. Fakultative Begleitsymptome sind sensorische Symptome (Dysästhesien, Schmerzen, Hyposmie), vegetative Symptome (Störungen von Blutdruck und/oder Temperaturregulation, Blasen-/ Darmfunktion sowie sexuellen Funktionen), psychische Symptome (Depression), Schlafstörungen, kognitive Symptome (frontale Störungen, Demenz). Die überwiegende Mehrzahl der Patienten mit Parkinson Syndrom mit den typischen motorischen Zeichen leidet unter der idiopathischen Parkinson Krankheit (mit Lewy-Körper Pathologie), die langsam progredient verläuft. Parkinson Erkrankungen, die vor dem 40. Lebensjahr auftreten, werden „früh beginnend“, diejenigen, die vor dem 21. Lebensjahr beginnen, „juvenil“ genannt. Der Vielzahl and genetischen (Mit-)Ursachen des Parkinson Syndroms wird mit einem umfangreichen panel Rechnung getragen, alle bekannten Erbgänge sind vertreten. Monogen bedingte Parkinson Erkrankungen machen allerdings nur 5-10% des gesamten Parkinson Spektrums aus. Die DNA-diagnostische Ausbeute ist auch in der juvenilen Parkinson Untergruppe mit bis zu 15% entdeckter pathogener Sequenzveränderungen niedrig. Unauffällige genetische Befunde bedeuten keinen sicheren Ausschluss der neurologischen Verdachtsdiagnose.

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1223/

• Alias: Morbus Parkinson; Parkinson disease
• Alias: Parkinson's disease
• Alias: Primary parkinsonism
• Allelic: 3-methylglutaconic aciduria, type VIII (HTRA2)
• Allelic: Amyotrophic lateral sclerosis, susceptibility to (DCTN1)
• Allelic: Amyotrophic lateral sclerosis, susceptibility to, 13 (ATXN2)
• Allelic: Aphasia, primary progressive (GRN)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2X (SPG11)
• Allelic: Combined SAP deficiency (PSAP)
• Allelic: Dementia, Lewy body (SNCA)
• Allelic: Developmental + epileptic encephalopathy 53 (SYNJ1)
• Allelic: Gaucher disease, atypical (PSAP)
• Allelic: Gaucher disease, perinatal lethal (GBA1)
• Allelic: Gaucher disease, type I, II, III, IIIC (GBA1)
• Allelic: Hyperostosis cranalis interna (SLC39A14)
• Allelic: Hyperphenylalaninemia, BH4-deficient, B (GCH1)
• Allelic: Infantile neuroaxonal dystrophy 1 (PLA2G6)
• Allelic: Intellectual developmental disorder, XL 72 (RAB39B)
• Allelic: Intellectual developmental disorder, XL syndromic 33 (TAF1)
• Allelic: Krabbe disease, atypical (PSAP)
• Allelic: Lewy body dementia, susceptibility to (GBA1)
• Allelic: Lopes-Maciel-Rodan syndrome (HTT)
• Allelic: Metachromatic leukodystrophy due to SAP-b deficiency (PSAP)
• Allelic: Neuronopathy, distal hereditary motor, type VIIBV
• Allelic: Nicotine dependence, protection against (SLC6A3)
• Allelic: Optic atrophy 3 with cataract (OPA3)
• 3-methylglutaconic aciduria, type III (OPA3)
• Amyotrophic lateral sclerosis 5, juvenile (SPG11)
• Brain abnormalities, neurodegeneration + dysosteosclerosis (CSF1R)
• CAPOS s. Cerebellar Ataxia, areflexia, Pes cavus, Optic atrophy, Sensorineural hearing loss (ATP1A3)
• Ceroid lipofuscinosis, neuronal, 11 (GRN)
• Chediak-Higashi syndrome (LYST)
• Congenital hypotonia, epilepsy, developmental delay, + digital anomalies (ATN1)
• Dementia, frontotemporal, with or without parkinsonism (MAPT)
• Dentatorubral-pallidoluysian atrophy (ATN1_CAG)
• Dystonia 16 (PRKRA)
• Dystonia 4, torsion, AD (TUBB4A)
• Dystonia, DOPA-responsive, with/-out hyperphenylalaninemia (GCH1)
• Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (SPR)
• Dystonia-12 (ATP1A3)
• Dystonia-12 (C19orf12)
• Dystonia-Parkinsonism, X (TAF1)
• Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (C9orf72_GGGGCC)
• Frontotemporal lobar degeneration with ubiquitin-positive inclusions (GRN)
• HARP syndrome, Hypoprebetalipoproteinemia, Acanthocytosis, Ret. pigm., Pallidal degeneration (PANK2)
• Huntington disease (HTT_CAG)
• Huntington disease-like 2 (JPH3_CAG)
• Hyperferritinemia-cataract syndrome (FTL)
• Hypermanganesemia with dystonia 1 (SLC30A10)
• Hypermanganesemia with dystonia 2 (SLC39A14)
• Kufor-Rakeb syndrome (ATP13A2)
• L-ferritin deficiency, AD, AR (FTL)
• Leukodystrophy, hypomyelinating, 6 (TUBB4A)
• Leukoencephalopathy, diffuse hereditary, with spheroids (CSF1R)
• Leukoencephalopathy, diffuse hereditary, with spheroids 1 (CSF1R)
• Levodopa-responsive Parkinson disease +/- atypical features [GeneReviews] (PODXL)
• Machado-Joseph disease (ATXN3_CAG)
• 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 (C19orf12)
• Neurodegeneration with brain iron accumulation 5 (WDR45)
• Neurodegeneration with brain iron accumulation 6 (COASY)
• Parkinson disease 1 (SNCA)
• Parkinson disease 11 (GIGYF2)
• Parkinson disease 13 (HTRA2)
• 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 2, juvenile (PRKN)
• Parkinson disease 20, early-onset (SYNJ1)
• Parkinson disease 22, AD (CHCHD2)
• Parkinson disease 23, AR, early onset (VPS13C)
• Parkinson disease 24, AD, susceptibility to (PSAP)
• Parkinson disease 4 (SNCA)
• Parkinson disease 5, susceptibility to (UCHL1)
• Parkinson disease 6, early onset (PINK1)
• Parkinson disease 7, AR early-onset (PARK7)
• Parkinson disease 8 (LRRK2)
• Parkinson disease 9, Kufor-Rakeb, Pallidopyramid. deg. + supranucl. upgaze paresis, dement (ATP13A2)
• Parkinson disease, late-onset, susceptibility to (ATXN2:CAG)
• Parkinson disease, late-onset, susceptibility to (GBA1)
• Parkinson disease, susceptibility to (MAPT)
• Parkinson disease, susceptibility to (TBP_CAG)
• Parkinsonism, intellectual disability (PTRHD1)
• Parkinsonism-dystonia, infantile, 1 (SLC6A3)
• Perry syndrome, Parkinsonism, alveolar hypoventil., mental depression (DCTN1)
• Pick disease (MAPT)
• Pontocerebellar hypoplasia, type 12 (COASY)
• Segawa syndrome, AR (TH)
• Spastic paraplegia 11, AR (SPG11)
• Spastic paraplegia 43, AR (C19orf12)
• Spastic paraplegia 79A, AD (UCHL1)
• Spastic paraplegia 79B, AR (UCHL1)
• Spinocerebellar ataxia 1 (ATXN1_CAG)
• Spinocerebellar ataxia 12 (PPP2R2B)
• Spinocerebellar ataxia 17 (TBP_CAG)
• Spinocerebellar ataxia 2 (ATXN2_CAG)
• Supranuclear palsy, progressive (MAPT)
• Supranuclear palsy, progressive atypical (MAPT)
• Waisman syndrome, Parkinsonism, early onset, mental retardation (RAB39B)