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HEREDITARY ATAXIA: RECESSIVE, CONGENITAL & X-LINKED 106

Recessive Ataxia: Syndromes
  General
  AAA: AAAS; 12q13
  Abetalipoproteinemia: MTTP; 4q23
  ARCA
    1 (SCAR8): SYNE1; 6q25
    2 (SCAR9): CABC1; 1q42
    PNPLA6: 19p13
    Retardation (SCAR11): SYT14; 1q32
  Ataxia +
    Epilepsy
      Eye disorders: COL18A1; 21q22
      Mental retardation
        CDG1C: ALG6; 1p31
        Dravet (EIEE6): SCN1A; 2q24
        SCAR12: WWOX; 16q23
        SCAR15: KIAA0226; 3q29
        SCAR20: SNX14; 6q14
        SCAR22: VWA3B; 2q11
        SCAR23: TDP2; 6p22
      Myoclonus
        EPM1B: PRICKLE1; 12q12
        EPM4 (Dem PN): SCARB2; 4q21
        EPM6: GOSR2; 17q21
        Unverricht-Lundborg: CSTB; 21q22
        Opsoclonus: KCTD7; 7q11
    Motor Neuropathy
      Laryngeal paralysis
      PEX10; 1p36
      SCAR10: ANO10; 3p22
      Spastic ataxia: CHP1; 15q15
    Neuropathy
      FRDA: FXN; 9q21
      SCAN1: TDP1; 14q31
      SH3TC2: 5q32
      TWNK: 10q24
    Upgaze palsy
  Ataxia-Oculomotor Apraxia (AOA)
    AOA1: Aprataxin (APTX); 9p21
    AOA2 (SCAR1): Senataxin; 9q34
    AOA3: PIK3R5; 17p13
    AOA4: PNKP; 19q13
    AOA: COQ5; 12q24
    AOA: GRID2; 4q22
    AOA: XRCC1; 19q13
    Ataxia + Ocular: ARV1; 1q42
    HADDTS: CTBP1; 4p16; Dominant
    PCH1B: EXOSC3; 9p13
    Ataxia & Cysts: LAMA1; 18p11
    Cerebro-Renal: SLC30A9; 4p13
    Joubert syndromes
    Dominant

  Ataxia telangectasia (AT)
    AT: ATM; 11q22
    AT-like 1 (ATLD1): MRE11A; 11q21
    AT-like 2 (ATLD2): PCNA; 20p12
    RIDDLE: RNF168; 3q29
  ATITHS: POU4F1; 13q31
  CANVAS: RFC1; 4p14
  Cardiac
    Dilated +: DNAJC19; 3q26
    CABAC: EXOSC5; 19q13
  Cataracts: UBA5; 3q22
  CAVIPMR: EMC1; 1p36
  Cayman ataxia: ATCAY; 19p13
  CCHLND: SLC33A1; 3q25
  CDG1a: PMM2
  Cerebelloparenchymal disorders (CPD)
    II, III, IV, V
  Charlevoix-Saguenay: Sacsin; 13q12
  Childhood (SCAR7): TPP1; 11p15
  CLN11: GRN; 17q21
  Cockayne Syndrome
    A: ERCC8; 5q12
    B: ERCC6; 10q11
  Coenzyme Q10 deficiency
    Aprataxin; 9p13
    ANO10; 3p22
  CONDCA: AGTPBP1; 9q21
  CONDSIAS: ADPRHL2; 1p34
  Congenital
  Cough + Sensory PN
  Cytochrome c Oxidase I: Mitochondrial
  DNA repair defects
  EOCA + Retained reflexes: 13q12
  Deafness
    Lichtenstein-Knorr (SCAR19): 1p36
    Optic atrophy (SCAR3): 6p21
  Friedreich ataxia (FRDA)
    1: Frataxin; 9q21
    2: 9p23
  Galactosialidosis: 20q13
  Galloway-Mowat
  Gillespie: ITPR1; 3p26
  Hepato-Neuropathy: SCYL1; 11q13
  Hypogonadism
  Infant onset (IOSCA): Ataxia +
    CNS & PN: Twinkle; 10q24
    SCAR14: SPTBN2; 11q13
  Joubert

  Karak: PLA2G6; 22q13
  Late onset: RFC1; 4p14
  Leukodystrophy
    HLD: 7, 8, 11, 21
    AR-LAD: RNF220; 1p34
  Leukoencephalopathy
    LBSL: DARS2; 1q25
    LKENP: AARS2; 6p21
    LKPAT: CLCN2; 3q27
    Vanishing white matter
  LGMD R18: TRAPPC11; 4q35
  Macular dystrophy
  MANSA: MAN2B1; 19p13
  Marinesco-Sjögren: SIL1; 5q31
  Metabolic disorders
  MIRAS: POLG1; 15q25
  Mitochondrial
  Multisystem
  Neurodevelopmental
    NED: TPR; 1q31
    NEDAMSS: IRF2BPL; 14q24
    NEDCAM: GEMIN5; 5q33
    NEDCAS: BRAT1; 7p22
    NEDIDHA: DOCK3; 3p21
    NEDMAS: SARS; 1p13
    ATP2B2: 3p25
  Niemann-Pick
  PCARP: 1q31
  PHARC: ABHD12; 20p11
  Pontocerebellar hypoplasia (PCH)
  Refsum
  Retinal degeneration
    ACO2; 2q13
    CTSD; 11p15
  Salla: SLC17A5; 6q13
  SANDO: POLG1; 15q25
  SCABD1: PEX6; 6p21
  SCAR4: VPS13D; 1p36
  SeSAME: KCNJ10; 1q23
  Slow eye movements
  Spastic
  SPAX3 (Portneuf): MARS2; 2q33
  SPG7: 16q24
  TACH (4H): POLR3A; 10q22
  Thalamic lesions & Adult onset
  Vitamin E deficient: ATTP; 8q12
  Xeroderma pigmentosum


SCAN
  1: TDP1; 14q32
  2: SETX; 9q34
  3: COA7; 1p32

SCAR
  1 (AOA2): Senataxin; 9q34
  2 (CLA1): PMPCA; 9q34
  3 (SCABD2): SLC25A2; 8q24
  4 (SCASI): VPS13D; 1p36
  5 (GAMOS): WDR73; 15q23
  6 (Cerebellar ataxia 3): 20q11
  7 (Childhood): TPP1; 11p15
  8 (ARCA1): SYNE1; 6q25
  9 (ARCA2): COQ8A; 1q42
  10 (+ Motor PN): ANO10; 3p22
  11 (+ MR): SYT14; 1q32
  12 (Seiz + MR): WWOX; 16q23
  13: GRM1; 6q24
  14: SPTBN2; 11q13
  15: KIAA0226; 3q29
  16: STUB1; 16p13
  17: CWF19L1; 10q24
  18: GRID2; 4q22
  19: SLC9A1; 1p36
  20: SNX14; 6q14
  21: SCYL1; 11q13
  22: VWA3B; 2q11
  23: TDP2; 6p22
  24: UBA5; 3q22
  25: ATG5; 6q21
  26: XRCC1; 19q13
  27: GDAP2; 1p12
  28: THG1L; 5q33
  29: VPS41; 7p14
  30: PITRM1; 10p15
  31: ATG7; 3p25
  32: PRDX3; 10q26
  33: RNU12; 22q13
X-linked ataxias
  AIFM1
  Arts Syndrome: PRPS1
  Ataxia, Epilepsy & MR: OPHN1
  Brain malformation: CASK
  Congenital
  Mental retardation-Epilepsy: SLC9A6
  Pelizaeus-Merzbacher variant: PLP
  Pyruvate dehydrogenase E1-α
  Rett syndrome: MECP2
  SCAX
    1 (CLA2): ATP2B3
    2 (Extrapyramidal)
    4
    5
  Sideroblastic anemia: ABCB7
  FXTAS: FMR1; Xq27

Other ataxia syndromes
  Acquired
  Congenital
  DNA repair defects
  DNA repeat disorders
  Dominant
  Glycosylation disorders
  Hypogonadism
  Joubert
  Metabolic
  Mitochondrial
  Nephro-CNS (GAMOS)
  Pontocerebellar hypoplasia (PCH)
  Quadrupedal (CAMRQ)
  Refsum
  Spastic
  X-linked

Recessive Ataxia
  Laboratory
  Neuromuscular associations
  Proteins

RECESSIVE ATAXIAS: General 129
Neuromuscular-Associated
Protein Types
Nuclear
Mitochondrial

Lipid
Signal Transduction Lysosome Peroxisome Vesicle Traffic Protein Quality Control
Laboratory Features
Acanthocyes: ABL
Albumin low: AOA1; SCAN1
α-fetoprotein high: AOA2; AT
Cholestanol high: CTX
Cholesterol high: AOA1; AOA2; SCAN1
Coenzyme Q10 (muscle) low: AOA1; SCAR9; APTX
Hexosaminidase A low: LOTS
Immunoglobulins low: AT;ATLD1
Lactate high: SCAR9
Radiosensitivity: AT;ATLD1
Gonadotropins low: PNPLA6; RNF216; SCAR16
Very long chain fatty acids (Peroxisomal): AMACR; PEX; Refsum
Vitamin E low: ABL; AVED

RECESSIVE ATAXIAS


Friedreich Ataxia 2

  FRDA (Frataxin) ; Chromosome 9q21.11; Recessive
  FRDA2; Chromosome 9p23-p11; Recessive 11

Frataxin protein
Genetic features
Neurological features
Pathology
Systemic features
Variant syndromes

From Bramwell: Atlas of Clinical Medicine

Friedreich Ataxia

From Wikipedia

Ataxia with selective Vitamin E deficiency (AVED) 78
  α-Tocopherol transfer protein (ATTP; TTPA) ; Chromosome 8q12.3   Abetalipoproteinemia; Chromosome 4q24


Infantile Onset Spinocerebellar Ataxia (IOSCA) 29
  Twinkle (c10orf2) ; Chromosome 10q24.31; Recessive

SCAR14: Infantile Onset Spinocerebellar Ataxia & Psychomotor Delay (SPARCA1) 74
  β-Spectrin, nonerythrocytic, 2 (β-III Spectrin; SPTBN2) ; Chromosome 11q13.2; Recessive
Baltic Myoclonus (Unverricht-Lundborg)
  Cystatin B (CSTB) ; Chromosome 21q22.3; Recessive
Opsoclonus-Myoclonus-Ataxia 68
  KCTD7 ; Chromosome 7q11.21; Recessive
Progresssive Myoclonus Epilepsy-Ataxia Syndrome (EPM1B) 46
  PRICKLE1 ; Chromosome 12q12; Recessive
Marinesco-Sjögren
  SIL1 Chromosome 5q31.2; Recessive
Charlevoix-Saguenay - Spastic Ataxia (ARSACS; SPAX 6)
  Sacsin (SACS) ; Chromosome 13q12.12; Recessive
  • Epidemiology
    • Family locations: French-Canadian (Quebec); Tunisia 3; Worldwide
  • Genetics
  • Sacsin protein
  • Clinical
    • Onset: Early
      • Age: Range 1 to 20 years; Mean 4 years
      • More severe & earlier onset in French-Canadian families
      • Never walk normally in French-Canadian families
      • Ataxia: Gait
    • Neurologic
      • Cerebellar
        • Ataxia: Dysarthria; Gait disorder
        • Ocular: Nystagmus (100%); Poor ocular pursuit
      • Eye
        • Conjugate gaze defects
        • Retina: Prominent myelinated nerve fibers (Variable frequency)
      • Motor
        • Spasticity
          • Paraparesis with gait disorder: Most patients
          • Extensor plantar responses
          • Progressive
          • No spasticity: Homozygous Phe304Ser mutation
        • Distal wasting & weakness
          • Legs > Arms
          • More apparent in older patients
      • Sensory: Loss of deep sensations
      • Tendon reflexes: Brisk except at ankles
      • Bladder: Urgency in 65%
      • Dystonia: Mild; Occasional
    • Systemic
      • Mitral valve prolapse
      • Pes cavus & Hammer toes: Some patients
    • Progression
      • Very slow; Little change after 20 years
      • Variable among family members
      • Some patients in wheelchair at 30 years
  • Laboratory
    • Electrophysiology
      • NCV
        • Sensory nerve conduction potentials: Absent
        • CMAPs: Small
        • Conduction velocities: Mildly slow
        • Distal latencies: May be prolonged
      • EMG: Denervation of distal muscles
      • Sensory evoked potentials: Abnormal
    • Nerve biopsy
      • Large myelinated axons: Reduced
      • Regenerating clusters
      • Occasional onion bulbs & thinly myelinated axons
    • Muscle: Neurogenic atrophy
    • Visual evoked responses: Delayed
    • CT scan: Cerebellar atrophy of superior vermis & anterior lobes
    • MRI
      • Cerebellum: Vermian atrophy
      • Brainstem (pons & middle cerebellar peduncles): Linear hypointensities (T2)
      • Muscle
        • Fatty change
          • Distal legs; Medial gastrocnemius & foot muscles
          • Symmetric
        • Relatively preserved: Thighs; Lateral gastrocnemius
    • CNS Pathology
      • Superior vermal & anterior lobe cerebellar atrophy
      • Absent Purkinje cells
  • SACS Variant syndromes
    • Ataxia with no spasticity or myelinated retinal axons
      • Homozygous nonsense mutation: Arg2119X
    • Ataxia with no spasticity
    • SACS variant: Axonal neuropathy, early onset, Recessive (HMSN) 112
      • Epidemiology: 9 families
      • Genetics
        • Inheritance: Recessive
        • SACS Mutations
          • Type: Misense or Stop
          • May be same as seen in full SACS syndrome
      • Clinical
        • Onset age: 1 to 15 years
        • Weakness: Distal; Legs & Arms
        • Sensory loss: Distal; Large fiber modalities; Ataxia
        • DTRs: Reduced or Normal
        • Pes cavus
        • Nystagmus (60%)
        • Spasticity: None
        • Disease course: Slow progression
      • Laboratory
        • Brain MRI
          • Pons: Linear hypointensities
          • Cerebellum: Superior vermis atrophy
        • NCV: Motor & Sensory axon loss
          • CMAPs: Absent or Reduced amplitude in legs
          • SNAPs: Absent or Reduced amplitude
          • NCV: 20 to 44 m/s
        • Nerve biopsy
          • Axon loss: Large & Small
          • Myelin: Increased folding

From H Topaloglu
Retina: Myelinated Axons


ARSACS

Cerebellum: Vermis Atrophy



Pons: Linear T2 hypointensities (Arrow)
From: R Bucelli, W Zhao & B Trikamji

Cayman Ataxia
  ATCAY (Caytaxin) ; Chromosome 19p13.3; Recessive
Early onset cerebellar ataxia with retained tendon reflexes (EOCA)
  Chromosome 13q11-12 + Other loci; Recessive
SCAR7: Cerebellar ataxia, Childhood onset
  Tripeptidyl peptidase I (TPP1; CLN2) ; Chromosome 11p15.4; Recessive
Cerebellar ataxia, Retinal degeneration & Cognitive decline
  Cathepsin D (CTSD) ; Chromosome 11p15.5; Recessive
Ataxia with Oculomotor apraxia 1 (AOA1) 9
  Aprataxin (APTX) ; Chromosome 9p21.1; Recessive
Cerebellar ataxia with Muscle coenzyme Q10 deficiency (EAOH) 1
  Aprataxin (APTX) ; Chromosome 9p21.1; Recessive
SCAR9: Cerebellar ataxia, Seizures and Ubiquinone deficiency (ARCA2; COQ10D4) 39
  Chaperone-activity of BC1 complex-like (CABC1, COQ8, COQ8A, ADCK3) ; Chromosome 1q42.13; Recessive or Sporadic
SCAR11: Cerebellar Ataxia with Psychomotor Retardation (ARCA) 60
  Synaptotagmin 14 (SYT14) ; Chromosome 1q32.2; Recessive
SCAR1: Ataxia with Oculomotor apraxia 2 (AOA2; SCAN2; ATX-SETX) 8
  Senataxin (SETX) ; Chromosome 9q34.13; Recessive
Ataxia with Oculomotor Apraxia 3 (AOA3) 62
  Phosphatidylinositol 3-kinase, regulatory subunit 5 (PIK3R5) ; Chromosome 17p13.1; Recessive
Ataxia with Oculomotor Apraxia 4 (AOA4) 84
  Polynucleotide kinase 3-prime phosphatase (PNKP) ; Chromosome 19q13.33; Recessive
SCAR3: Spinocerebellar ataxia with blindness and deafness (SCABD2) 105
  SLC52A2 (RFT3; GPR172A; RFVT2) ; Chromosome 8q24.3; Recessive
Cerebelloparenchymal disorder II (CPD II)

Cerebelloparenchymal disorder V (CPD V; Dyssynergia cerebellaris myoclonica)

Leukoencephalopathies with Vanishing White Matter (VWM)
VWM1
  Translocation initiation factor eIF2B1, α subunit ; Chromosome 12q24.31; Recessive
VWM2
  Translocation initiation factor eIF2B2, β subunit ; Chromosome 14q24.3; Recessive
VWM3
  Translocation initiation factor eIF2B3, γ subunit ; Chromosome 1p34.1; Recessive
VWM4
  Translocation initiation factor eIF2B4, δ subunit ; Chromosome 2p23.3; Recessive
VWM5
  Translocation initiation factor eIF2B5, ε subunit ; Chromosome 3q27.1; Recessive
VWM (MC1DN10)
  MYC-induced mitochondrial protein (B17.2L; Mimitin) ; Chromosome 5q12.1; Recessive
Other
  Dominant
  • VWM Nosology: Other names
    • Childhood ataxia with difuse hypomyelination
    • Myelinosclerosis centralis diffusa
    • VWM5: Cree leukoencephalopathy
  • Genetics
    • ~84 mutations identified
    • Most commonly mutated gene: eIF2B5, R113H
    • Phenotype relation
      • Milder (Onset > 5 yrs): Mutations
        • Non-conserved amino acids: R113H (EIF2B5) & E213G (EIF2B2)
      • Severe: Mutations
        • Highly conserved amino acids (R195H in EIF2B5)
    • Allelic disorders
  • eIF2B complex
    • Eukaryotic translation initiation factor eIF2B
    • 5 Subunits: α, β, γ, δ, ε
    • Functions
      • Initiation & regulation of translation of RNA into protein
      • Especially involved with stress or fever
      • Catalyzes exchange of eukaryotic initiation factor 2-bound GDP for GTP
    • eIF2B mutation effects
      • Mitochondrial dysfunction
      • Astrocyte disorder
  • Clinical
    • Onset age: Variable
      • Usual: Childhood
      • Occasional: Adult onset
    • Course
      • Initial childhood motor & mental development: Normal or mildly delayed
      • Chronic progressive
      • Episodic
        • Deterioration after infections & minor head trauma
        • Periods of coma
      • Death: After years to decades
    • Neurologic signs: Spastic ataxia
      • Ataxia
      • Spasticity
      • Occasional
        • Optic atrophy
        • Epilepsy
        • Mental dysfunction
        • Polyneuropathy: Severe patient
          • Pathology: Mild loss of myelinated axons
          • NCV: Mild Slowing
  • MRI
    • Diffuse cerebral hemispheric leukoencephalopathy
    • Areas of abnormal white matter have high T2 signal intensity like CSF
  • Pathology
    • Cavitating orthochromatic leukodystrophy without atrophy: No plaques
    • Location: Hemispheric white matter
    • Oligodendrocytes: Increased density without mitotic activity
    • Astrocytes: Shrinkage; Reduced number in perivascular regions
  • Variant: Ovarioleukodystrophy 28
    • Epidemiology: 1 family; Mother & son
    • Genetics
      • Mutations in eIF2B2, eIF2B4 & eIF2B5
      • Inheritance: Dominant
    • Clinical
      • Adult onset: 4th decade
      • Somnolence, mental confusion & hemiparesis: After URI with fever
Leukoencephalopathy with Vanishing WM
eIF2B2 mutation

T2 Flair

T2

T1

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) 33
  Mitochondrial aspartyl-tRNA synthetase (DARS2) ; Chromosome 1q25.1; Recessive

Leukoencephalopathy with ataxia (LKPAT) 143
  Chloride channel 2 (CLCN2) ; Chromosome 3q27.1; Recessive

Ataxia with Leukodystrophy (HLD11)
  POLR1C polymerase (RNA) I (DNA directed) polypeptide C (POLR1C) ; Chromosome 6p21.1; Recessive

Tremor–Ataxia with Central Hypomyelination (TACH) Leukodystrophy 56
  POLR3A polymerase (RNA) III (DNA directed) polypeptide A, 155kDa (POLR3A) ; Chromosome 10q22.3; Recessive

Hypomyelinating leukodystrophy 8 (HLD8)
  POLR3B polymerase (RNA) III subunit B (POLR3B) ; Chromosome 12q23.3; Recessive

Hypomyelinating Leukodystrophy 21 (HLD21) 119
  POLR3K polymerase (RNA) III subunit B (POLR3K) ; Chromosome 16p13.3; Recessive

Leukodystrophy, Hypomyelinating 23 + Ataxia, Deafness, Liver Δ & Cardiomyopathy (AR-LAD; HLD23) 125
  Ring Finger Protein 220 (RNF220) ; Chromosome 1p34.1; Recessive

Salla disease (SD)
  Solute carrier family 17, Member 5 (SLC17A5; Sialin) ; Chromosome 6q13; Recessive
Ataxia with Laryngeal abductor paralysis & Motor neuropathy 10
  Recessive
Ataxia: Adult onset with Thalamic lesions 12
  POLG; Chromosome 15q26.1; Recessive
Ataxia with Bull’s-eye Macular Dystrophy 16
  Recessive

SCAR4: Spinocerebellar ataxia with saccadic intrusions (SCASI; SCA24) 107
  Vacuolar protein sorting 13, yeast, homolog of, D (VPS13D) Chromosome 1p36.22-p36.21; Recessive

Spinocerebellar ataxia with slow eye movements (SDSEM)
  Recessive
Portneuf spastic ataxia with leukoencephalopathy (ARSAL; SPAX3) 21
  Methionyl Aminoacyl-tRNA Synthetase 2 (MARS2) ; Chromosome 2q33.1; Recessive
Karak syndrome (NBIA2B)
  Phospholipase A2, Group VI (PLA2G6) ; Chromosome 22q13.1; Recessive
Ataxia with upward gaze palsy 25
  Recessive
SCAR8: Pure cerebellar ataxia (ARCA1; Beauce ataxia) 32
  Synaptic nuclear envelope protein 1 (SYNE1; Nesprin 1) ; Chromosome 6q25.1-q25.2; Recessive

SCAR12: Ataxia with Epilepsy & Mental retardation 34
  WW domain-containing oxidoreductase (WWOX) : Chromosome 16q23.1-q23.2; Recessive
SCAR23: Ataxia with Epilepsy & Mental retardation 80
  TRAF- & TNF Receptor-associated protein (TDP2; TTRAP) ; Chromosome 6p22.3; Recessive
SCAR15: Ataxia with Epilepsy & Mental retardation (Salih) 73
  Run domain- & cysteine-rich domain-containing beclin-1-interacting protein (RUBCN; KIAA0226; Rubicon; Rundataxin) ; Chromosome 3q29; Recessive
SCAR20: Ataxia with Mental retardation 83
  Sorting Nexin 14 (SNX14) ; Chromosome 6q14.3; Recessive
SCAR22: Ataxia with Mental retardation & Pyramidal features 87
  von Willebrand factor A domain-containing protein 3B (VWA3B) ; Chromosome 2q11.2; Recessive
SCAR17: Congenital Ataxia with Mental retardation
  CWF19-like protein 1 (CWF19L1) ; Chromosome 10q24.31; Recessive
Cerebellar hypoplasia, Mental retardation & Quadrupedal locomotion (CAMRQ2)
  WD repeat-containing protein 81 (WDR81) ; Chromosome 17p13.3; Recessive

Ataxia + Mental Retardation, mild & Quadrupedal locomotion (CAMRQ3) 50
  Carbonic anhydrase VIII (CA8; CARP) ; Chromosome 8q12.1; Recessive

Ataxia + Mental Retardation & Quadrupedal locomotion (CAMRQ4) 69
  ATPase, Class I, Type 8A, Member 2 (ATP8A2) ; Chromosome 13q12.13; Recessive
Ataxia + Epilepsy + Eye Disorders 48
  Collagen 18A1 ; Chromosome 21q22.3; Recessive

Ataxia + Progressive Myoclonus Epilepsy (North Sea; EPM6) 59
  Golgi Snap Receptor Member Complex 2 (GOSR2; GS27; Membrin) ; Chromosome 17q21.32; Recessive
Ataxia + Neurodegeneration & Epilepsy (NEDAMSS) 108
  Interferon regulatory factor 2-binding protein like (IRF2BPL; EAP1; c14orf4) ; Chromosome 14q24.3; Recessive
Neurodevelopmental disorder with Cerebellar atrophy ± Seizures (NEDCAS)
  BRCA1-associated atm activator 1 (BRAT1) ; Chromosome 7p22.3; Recessive
Neurodevelopmental Disorder with Impaired intellectual Development, Hypotonia & Ataxia (NEDIDHA)
  Dedicator of cytokinesis 3 (DOCK3) ; Chromosome 3p21.2; Recessive
Neurodevelopmental Disorder + Ataxia (NEDCAM) 126
  Gem Nuclear Organelle-Associated Protein (GEMIN5) ; Chromosome 5q33.2; Recessive
Neurodevelopmental Disorder, Microcephaly + Ataxia 127
  Translocated Promoter Region, Nuclear basket protein (TPR) ; Chromosome 1q31.1; Recessive
SeSAME 49
  KCNJ10 (Kir4.1) ; Chromosome 1q23.2; Recessive

Ataxia + Motor Neuropathy 55
  Peroxisome biogenesis factor 10 (PEX10) ; Chromosome 1p36.32; Recessive
SCAR10: Ataxia + Motor Neuropathy 2 (ARCA3) 57
  Anoctamin 10 (ANO10; TMEM 16K) ; Chromosome 3p22.1; Recessive

SPAX9: Spastic Ataxia + Motor Neuropathy 103
  Calcineurin homologous protein-1 (CHP1) ; Chromosome 15q15.1; Recessive

SCAR18: Ataxia, Oculomotor Apraxia + Cerebellar Atrophy 72
  Glutamate receptor, ionotropic, delta 2 (GRID2) ; Chromosome 4q22.1-q22.2; Recessive

SCAR19: Ataxia-Deafness (Lichtenstein-Knorr syndrome )
  Solute carrier family 9, member 1 (SLC9A1; NHE1) ; Chromosome 1p36.11; Recessive

SCAR21: Hepatocerebellar-Neuropathy 93
  SCY1-Like 1 (SCYL1) ; Chromosome 11q13.1; Recessive

SCAR24: Ataxia + Cataracts, Childhood onset 94
  Ubiquitin-activating enzyme E1 domain-containing 1 (UBA5; UBE1DC1) ; Chromosome 3q22.1; Recessive

SCAR25: Spinocerebellar ataxia, Autosomal recessive 25
  Autophagy 5, S. Cerevisiae, homolog of 1 (ATG5) ; Chromosome 6q21; Recessive

SCAR26: Spinocerebellar ataxia, Autosomal recessive 26
  X-ray repair, complementing defective, in Chinese hamster, 1 (XRCC1) ; Chromosome 19q13.31; Recessive

SCAR27: Ataxia + Spasticity & Dementia 109
  Ganglioside-induced differentiation-associated protein 2 (GDAP2) ; Chromosome 1p12; Recessive

Spinocerebellar ataxia with Axonal Neuropathy 3 (SCAN3) 104
  Cytochrome C oxidase assembly factor 7 (COA7) ; Chromosome 1p32.3; Recessive

Spinocerebellar ataxia with Blindness & Deafness 1 (SCABD1) 105
  Peroxisome biogenesis factor 6 (PEX6) ; Chromosome 6p21.1; Recessive

Ataxia, Cough + Sensory Neuropathy 75
  Recessive

Cerebellar atrophy, Visual impairment & Psychomotor retardation (CAVIPMR)
  Endoplasmic reticulum membrane protein complex, Subunit 1 (EMC1) ; Chromosome 1p36.13; Recessive
SCAR28: Cerebellar atrophy, Developmental delay & Spasticity 96
  tRNA-Histidine Guanylyltransferase 1 like (THG1L) ; Chromosome 5q33.3; Recessive
Neurodegeneration, Childhood onset with Cerebellar Atrophy (CONDCA)
  ATP/GTP Binding Protein 1 (AGTPBP1; NNA1) ; Chromosome 9q21.33; Recessive
Neurodegeneration with Developmental Delay, Ataxia & Axonal Neuropathy (CONDSIAS) 111
  ADP-Ribosylhydrolase-like 2 (ADPRHL2; ARH3) ; Chromosome 1p34.3; Recessive
Ataxia, Intention tremor & Hypotonia syndrome, Childhood-onset (ATITHS)
  ADP-Ribosylhydrolase-like 2 (POU4F1; BRN3A) ; Chromosome 13q31.1; Recessive
Cerebellar ataxia, Brain abnormalities & Cardiac conduction defects (CABAC)
  Exosome Component 5 (EXOSC5) ; Chromosome 19q13.2; Recessive
Cerebro-Renal syndrome
  Solute carrier family 30 (Zinc transporter), Member (SLC30A9; ZnT-9) ; Chromosome 4p13; Recessive
Galactosialidosis
  Cathepsin A (CTSA) ; Chromosome 20q13.12; Recessive
α-Mannosidosis
  Mannosidase, alpha, class 2b, member 1 (MAN2B1; LAMAN) ; Chromosome 19p13.13; Recessive
Ataxia + Ocular disorders
  ARV1 homolog, fatty acid homeostasis modulator (ARV1) ; Chromosome 1q42.2; Recessive

CONGENITAL ATAXIC DISORDERS

General
Autosomal Recessive
Aprosencephaly + Cerebellar dysgenesis
Ataxia-Mental retardation: Xq24-q27
Behr syndrome
CADEDS: KCNMA1; 10q22
CCAFCA: FRMD4A; 10p13
CDG1A: PMM2; 16p13
Cerebellar ataxia 1
Cerebellar & Pancreatic aplasia: PTF1A; 10p13
Cerebelloparenchymal disorder IV (Joubert)
Cerebellotrigeminaldermal dysplasia
Cerebral palsy, Ataxic: 9p12-q12
CHEGDD: OXR1; 8q23
CIMDAG: VPS4A; 16q22
COACH syndromes
Congenital muscular dystrophies
  Cerebellar atrophy
  Muscle-Eye-Brain Disorders
    Santavuori (Finnish): POMGNT1; 1p34
    Walker-Warburg
Dandy-Walker
  ZIC1 & ZIC4; 3q24
  FOXC1; 6p25
  SMG9: 19q13
ENDOVESLB: EN1; 2q14
Fibroblast growth factor receptor-3: 4p16
Gillespie
  ITPR1: 3p26
  PAX6: 11p13
 
Hoyeraal-Hreidarsson: Dyskerin; Xq28
Hypoplasia + Simple Cerebral Gyri: VLDLR; 9p24  
Joubert syndromes
Lissencephaly
  Cleft palate & Cerebellar hypoplasia
  Cerebellar hypoplasia: RELN; 7q22
MARCH: CEP55; 10q23
MCCCHCM: MAST1; 19p13
Microcephaly
  Brain malformation: CASK; Xp11
  Polymicrogyria & Corpus callosum agenesis: EOMES; 3p24
  MCHCCD
NEDAHM: SVBP; 1p34
NEDFACH: EXOC2; 6p25
NEDHCA: VPS41; 7p14
NEDHCAS: PIGK; 1p31
NEDSCAC: MED27; 9q34
Pitt-Hopkins: TCF-4; 18q21
Pontocerebellar hypoplasia (PCH)
Quadrupedal locomotion (CAMRQ)
  1: VLDLR; 9p24
  2: WDR81; 17p13
  3: CA8; 8q11
  4: ATP8A2; 13q12
SCAR
  5 (CAMOS): WDR73; 15q25
  6 (CLA3): 20q11
  13: GRM1; 6q24
  17: CWF19L1; 10q24
  25: ATG5; 6q21
X-Linked
Ataxia-Deafness
Ataxia, Epilepsy & MR: OPHN1; Xq12
Ataxia + Mental retardation
Brain malformation & Microcephaly (MICPCH): CASK; Xp11
CASM: Xpter-q13.1
Congenital ataxia: Xq23
Congenital ataxia + Severe mental retardation: Xq24
Hoyeraal-Hreidarsson Syndrome: Dyskerin; Xq28
Mental retardation & Muscle wasting: CUL4B; Xq24
SCAX
  1: ATP2B3; Xq28
  2
  3 (Ataxia-Deafness)
  5: Xq25
TARP: RBM10; Xp11

Autosomal Dominant
CANPMR: CAMTA1; 1p36
CLA4 (SCA15): ITPR1; 3p26
Lissencephaly: MACF1; 1p34 (de novo)
Retardation-Dyskinesia-Coma: CACNA1A; 19p13
Skeleton-skin-brain syndrome: FGFR-3; 4p16

CONGENITAL ATAXIAS: AUTOSOMAL RECESSIVE or SPORADIC


Joubert syndromes 26, 61

Joubert: General features

Types: Usually recessive
1: INPP5E; 9q34
2: TMEM216; 11q12
3: AHI1; 6q23
4: NPHP1; 2q13
5: CEP290; 12q21
6: TMEM67; 8q22
7: RPGRIP1L; 16q12
8: ARL13B; 3q11
9: CC2D2A; 4p15
10: OFD1 (CXORF5); Xp22
11: TTC21B; 2q24; Dominant
12: KIF7; 15q26
13: TCTN1; 12q24
14: TMEM237; 2q33
15: CEP41; 7q32
16: TMEM138; 11q12
17: CPLANE1; 5p13
18: TCTN3; 10q24
19: ZNF423; 16q12
20: TMEM231; 16q23
21: CSPP1; 8q13
22: PDE6D; 2q37
23: KIAA0586; 14q23
24: TCTN2; 12q24
25: CEP104; 1p36
26: KIAA0556; 16p12
27: B9D1; 17p11
28: MKS1; 17q22
29: TMEM107; 17p13
30: ARMC9; 2q37
31: CEP120; 5q23
32: SUFU; 10q24
33: PIBF1; 13q21
34: B9D2; 19q13
35: ARL3; 10q24
36: FAM149B1; 10q22
37: TOGARAM1; 14q21
38: KIAA0753; 17p13
39: TMEM218; 11q24
40: IFT74; 9p21
Joubert: EXOC8; 1q42
Joubert: C2CD3; 11q13
Joubert: SLC30A7; 1p21
COACH syndromes
  CC2D2A; 4p15
  TMEM67; 8q22
Nephronophthisis
  ATXN10; 22q13.31

From: A Paciorkowski
Molar Tooth Sign

Congenital Ataxias: Other


COACH syndromes
Cerebellar vermis hypoplasia, Oligophrenia, Ataxia, Colobomas, Hepatic fibrosis

1: TMEM67
2: CC2D2A
3: RPGRIP1L

Ponto-Cerebellar Hypoplasia

PCH1 + Spinal muscular atrophy
  PCH1A: VRK1; 14q32
  PCH1B: EXOSC3; 9p13
  PCH1C: EXOSC8; 13q13
  PCH1D: EXOSC9; 4q27
  PCH1E: SLC25A46; 5q22
    Lethal Congenital
  PCH1F: EXOSC1; 10q24
  PCH: KIF26B; 1q44
PCH2: Progressive cerebral atrophy
  PCH2A: TSEN54; 17q25
  PCH2B: TSEN2; 3p25
  PCH2C: TSEN34; 19q13
  PCH2D: SEPSECS; 4p15
  PCH2E: VPS53; 17p13
  PCH2F: TSEN15; 1q25

Also see: Congenital ataxia
PCH3: Progressive microcephaly (CLAM); PCLO; 7q21
PCH4: Fatal infantile: TSEN54; 17q25
PCH5: Fetal onset
PCH6: Pontocerebellar hypoplasia; RARS2; 6q15
PCH7: PCH + Hypogonadism; TOE1; 1p34
PCH8: PCH + Microcephaly; CHMP1A; 16q24
PCH9: PCH + Mega cisterna magna; AMPD2; 1p13
PCH10: PCH + Epilepsy; CLP1; 11p12
PCH11: TBC1D23; 3q12
PCH12: COASY; 17q21
PCH13: VPS51; 11q13
PCH14: PPIL1; 6p21
PCH15: CDC40; 6q21
PCH16: MINPP1; 10q23
PCH17: PRDM13; 6q16
PCH: HEATR5B; 2p22
PCH: MED17; 11q21
MIPCH: CASK; Xp11
PC Atrophy: SPTAN1; 9q34
PHRINL: ATAD3A; 1p36
GEMIN5: 5q33

CONGENITAL ATAXIA: X-LINKED

Late-onset Ataxia

Metabolic ataxias


X-LINKED ATAXIAS

Ataxia: Multisystem disorders
Mouse disorders
Patient information

Return to Ataxia Index
Return to Neuromuscular Home Page

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