Klinische FragestellungAtaxie, autosomal dominant [Erwachsenenalter]; Differentialdiagnose

1. X

 

40 dominant vererbte SCAs; häufigste Subtypen SCA1 (ATXN1 Gen, CAG-Repeats), SCA2 (ATXN2 Gen, CAG-Repeats), SCA3 (ATXN3 Gen, CAG-Repeats), SCA6 (>Hälfte aller SCAs; CACNA1A1 Gen, CAG-Repeats); ca. 15% Patienten mit sporadischer Ataxie trotz negativer Familienanamnese mit Mutation, meist SCA6. Dann in der Reihenfolge je nach Symptomatik: SCA7 (ATXN7 Gen, CAG-Repeats), SCA17 (TBP Gen, CAG-Repeats), SCA12 (PPP2R2B Gen, CAG-Repeats)...

2. NGS

 

Gruppe von Erkrankungen: Viele sich überschneidende, klinisch schwer zu unterscheidende Zeichen mit meist gemeinsamen Merkmalen wie Gangataxie, Dysarthrie, Sakkaden- Augenbewegungen; spezifischere Merkmale einiger Ataxien wie Augenerkrankungen, extrapyramidale Zeichen und periphere Nerven Symptome, intellektuelle Verschlechterung, Krampfanfälle, Symptome oberer Motoneurone, Tremor

• Alias: Erbliche Ataxie, Erwachsene
• Alias: Hereditary ataxia, AD, adult onset
• Allelic: Alternating hemiplegia of childhood 1 (ATP1A2)
• Allelic: Alternating hemiplegia of childhood 2 (ATP1A3)
• Allelic: Brugada syndrome 9 (KCND3)
• Allelic: Combined oxidative phosphorylation deficiency 13 (PNPT1)
• Allelic: Congenital hypotonia, epilepsy, developmental delay + digital anomalies (ATN1_CAG)
• Allelic: Convulsions, familial infantile, with paroxysmal choreoathetosis (PRRT2)
• Allelic: Creutzfeldt-Jakob disease (PRNP)
• Allelic: Deafness, AR 70, with/-out adult-onset neurodegeneration (PNPT1)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Allelic: Epilepsy, juvenile absence, susceptibility to, 2 (CLCN2)
• Allelic: Epilepsy, juvenile myoclonic, susceptibility to, 8 (CLCN2)
• Allelic: Epileptic encephalopathy, early infantile, 13 (SCN1A)
• Allelic: Epileptic encephalopathy, early infantile, 32 (KCNA2)
• Allelic: Epileptic encephalopathy, early infantile, 42 (CACNA1A)
• Allelic: Epileptic encephalopathy, early infantile, 6 [Dravet syndrome] (SCN1A)
• Allelic: Epileptic encephalopathy, early infantile, 7 (KCNQ2)
• Allelic: Febrile seizures, familial, 3A (SCN1A)
• Allelic: Fibrosis of extraocular muscles, congenital, 3A (TUBB3)
• Allelic: GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• Allelic: GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Allelic: Gerstmann-Straussler disease (PRNP)
• Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
• Allelic: Hyperaldosteronism, familial, type II (CLCN2)
• Allelic: Ichthyosis, spastic quadriplegia + mental retardation (ELOVL4)
• Allelic: Insomnia, fatal familial (PRNP)
• Allelic: Kuru, susceptibility to (PRNP)
• Allelic: Leukodystrophy, hypomyelinating, 6 (TUBB4A)
• Allelic: Migraine, familial hemiplegic, 1 (CACNA1A)
• Allelic: Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Allelic: Mitochondrial AR ataxia syndrome [includes SANDO + SCAE] (POLG)
• Allelic: Mitochondrial DNA depletion syndrome 14 [encephalocardiomyopathic type] (OPA1)
• Allelic: Monosomy 7 myelodysplasia + leukemia syndrome 1 (SAMD9L)
• Allelic: Myoclonus, familial, 2 (SCN1A)
• Allelic: Neuropathy, hereditary sensory, type IE (DNMT1)
• Allelic: Optic atrophy 1 (OPA1)
• Allelic: Optic atrophy 12 (AFG3L2)
• Allelic: Parkinson disease, susceptibility to (ATXN8OS)
• Allelic: Parkinson disease, susceptibility to (TBP_CAG)
• Allelic: Prion disease with protracted course (PRNP)
• Allelic: Progressive external ophthalmoplegia with mtDNA deletions, AD 3 (TWNK)
• Allelic: Progressive external ophthalmoplegia, AD 1/AR 1 (POLG)
• Allelic: Seizures, benign familial infantile, 2 (PRRT2)
• Allelic: Seizures, benign familial infantile, 5 (SCN1A)
• Allelic: Seizures, benign neonatal, 1 (KCNQ2)
• Allelic: Sensory ataxic neuropathy, dysarthria + ophthalmoparesis [SANDO] (POLG)
• Allelic: Spinocerebellar ataxia 29, congenital nonprogressive (ITPR1)
• Allelic: Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (CACNA1G)
• Allelic: Spinocerebellar ataxia with epilepsy [SCAE] (POLG)
• Allelic: Spinocerebellar ataxia, AR 13 (GRM1)
• Allelic: Spinocerebellar ataxia, AR 14 (SPTBN2)
• Allelic: Spinocerebellar ataxia, AR 16 (STUB1)
• Allelic: Stargardt disease 3 (ELOVL4)
• Allelic: Thyroid cancer, nonmedullary, 1 (NKX2-1)
• Alexander disease (GFAP)
• Ataxia, sensory, 1, AD (RNF170)
• Ataxia-pancytopenia syndrome (SAMD9L)
• Behr syndrome [early-onset optic atrophy, neurologic features, including ataxia] (OPA1)
• CAPOS [Cereb. ataxia, Areflexia, Pes cavus, Optic atrophy, Sensorin. hearing loss] syndrome (ATP1A3)
• Cerebellar ataxia, deafness + narcolepsy, AD (DNMT1)
• Cerebellar ataxia, nonprogressive, with mental retardation (CAMTA1)
• Cerebral amyloid angiopathy, PRNP-related (PRNP)
• Ceroid lipofuscinosis, neuronal, 4, Parry type (DNAJC5)
• Charcot-Marie-Tooth disease, axonal, type 2A2A + 2A2B (MFN2)
• Charcot-Marie-Tooth disease, axonal, type 2T (MME)
• Chorea, hereditary benign (NKX2-1)
• Choreoathetosis, hypothyroidism + neonatal respiratory distress (NKX2-1)
• Cognitive impairment with/-out cerebellar ataxia (SCN1A)
• Cortical dysplasia, complex, with other brain malformations 1 (TUBB3)
• Cortical dysplasia, complex, with other brain malformations 7 (TUBB2B)
• Dentatorubral-pallidoluysian atrophy (ATN1_CAG)
• Developmental + epileptic encephalopathy 66 (PACS2)
• Dyskinesia, familial, with facial myokymia (ADCY5)
• Dystonia 4, torsion, AD (TUBB4A)
• Dystonia 9 (SLC2A1)
• Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (SPR)
• Dystonia-12 (ATP1A3)
• Epilepsy, generalized, with febrile seizures plus, type 2 (SCN1A)
• Epilepsy, idiopathic generalized, susceptibility to, 11 (CLCN2)
• Episodic ataxia, type 2 (CACNA1A)
• Episodic ataxia, type 6 (SLC1A3)
• Episodic ataxia/myokymia syndrome (KCNA1)
• Episodic kinesigenic dyskinesia 1 (PRRT2)
• Gillespie syndrome [aniridia, cerebellar ataxia + mental retardation] (ITPR1)
• Hereditary motor and sensory neuropathy VIA (MFN2)
• Huntington disease-like 1 (PRNP)
• Hyperekplexia 1 (GLRA1)
• Hypotonia, ataxia + delayed development syndrome (EBF3)
• Intellectual developmental disorder with/-out epilepsy or cerebellar ataxia (RORA)
• Leukodystrophy, hypomyelinating, 16 (TMEM106B)
• Leukoencephalopathy with ataxia (CLCN2)
• Lissencephaly 3 (TUBA1A)
• Mental retardation, AD 5 (SYNGAP1)
• Migraine, familial basilar (ATP1A2)
• Migraine, familial hemiplegic, 2 (ATP1A2)
• Migraine, familial hemiplegic, 3 (SCN1A)
• Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
• Myokymia (KCNQ2)
• Myopathy, mitochondrial + ataxia (MSTO1)
• Neurodevelopmental disorder with regression, abnormal movements, loss of speech, seizures (IRF2BPL)
• Neurodevelopmental disorder with/-out variable brain abnormalities (MAPK8IP3)
• Optic atrophy plus syndrome (OPA1)
• Paroxysmal nonkinesigenic dyskinesia 1 (PNKD)
• Perrault syndrome 5 (TWNK)
• Spastic ataxia 5, AR (AFG3L2)
• Spinocerebellar ataxia 1 (ATXN1_CAG)
• Spinocerebellar ataxia 10 (ATXN10_ATTCT)
• Spinocerebellar ataxia 11 (TTBK2)
• Spinocerebellar ataxia 12 (PPP2R2B_CAG)
• Spinocerebellar ataxia 14 (PRKCG)
• Spinocerebellar ataxia 15 (ITPR1)
• Spinocerebellar ataxia 17 (TBP_CAG)
• Spinocerebellar ataxia 19 (KCND3)
• Spinocerebellar ataxia 21 (TMEM240)
• Spinocerebellar ataxia 23 (PDYN)
• Spinocerebellar ataxia 25 (PNPT1)
• Spinocerebellar ataxia 26 (EEF2)
• Spinocerebellar ataxia 27 (FGF14)
• Spinocerebellar ataxia 28 (AFG3L2)
• Spinocerebellar ataxia 34 (ELOVL4)
• Spinocerebellar ataxia 36 (NOP56_GGCCTG)
• Spinocerebellar ataxia 37 (DAB1)
• Spinocerebellar ataxia 41 (TRPC3)
• Spinocerebellar ataxia 42 (CACNA1G)
• Spinocerebellar ataxia 43 (MME)
• Spinocerebellar ataxia 44 (GRM1)
• Spinocerebellar ataxia 46 (PLD3)
• Spinocerebellar ataxia 47 (PUM1)
• Spinocerebellar ataxia 48 (STUB1)
• Spinocerebellar ataxia 5 (SPTBN2)
• Spinocerebellar ataxia 6 (CACNA1A + CACNA1A-CAG)
• Spinocerebellar ataxia 8 (ATXN8)
• Spinocerebellar ataxia 8 (ATXN8OS)
• Spinocerebellar ataxia, AR 20 [both, AD + AR; biallelic more severe disease; panelapp] 20 (SNX14)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)