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FAMILIAL SPINAL CORD SYNDROMES1

General principles

Familial Spastic Paraplegia (SPG)
  Dominant
    3A: Atlastin; 14q11
    4: Spastin; 2p22
    6: NIPA1; 15q11
    8: KIAA0196; 8q23
    9: 10q23
    10: KIF5A; 12q13
    12: 19q13
    13: HSPD1; 2q24
    17 (Silver): BSCL2; 11q13
    19: 9q33
    29: 1p31
    31: REEP1; 2p12
    33: ZFYVE27; 10q24
    36: 12q23
    37: 8p21
    38: 4p16
    41: 11p14
    42: SLC33A1; 3q24
    SPG + Dystonia: 2q24

  Recessive
    5: CYP7B1; 8q21
    5B
    7 (5C): Paraplegin; 16q24
    11: Spatacsin; 15q13
    14: 3q27-q28
    15: Spastizin; 14q22-q24
    18: 8p12
    20 (Troyer): Spartin; 13q12.3
    21 (Mast): Maspardin; 15q22
    23: 1q24
    24: 13q14
    25: 6q23
    26: 12p11
    27: 10q22
    28: 14q21
    30: 2q37
    32: 14q12
    35: 16q21
    39: PNPLA6; 19q13
    43: 19p13
    45: 10q24.3
    Infantile onset: Alsin; 2q33
    SPOAN: 11q13
    Cerebral palsy: 2q31
    Leukodystrophy & Dystonia: FA2H; 16q23
    Complicated SPG: GJA12; 1q41

  X-linked
    1: L1CAM; Xq28
    2: Proteolipid protein; Xq22
    16: Xq11
    34: Xq25
    Other: Deafness

Familial Spastic Paraplegia +...
  Ataxia
  CNS
  Dystonia
  Ocular
  PNS
  Systemic Disorders
Familial Spinal Cord Syndromes
  AAA syndrome: Aladin; 12q13
  Adrenomyeloneuropathy: ALDP; Xq28
  Alexander: GFAP; 17q21; Dominant
  Alzheimer's: Presenilin 1; 14q24; Dominant
  Arnold-Chiari Malformation
  Cataracts & GI reflux (SPG9): 10q23; Dominant
  Cavanagh's
  Cerebral palsy, spastic quadriplegic (CPSQ)
    CPSQ1: GAD1; 2q31
    CPSQ2: KANK1; 9p24
    CPSQ3: AP4M1; 7q22
  Cerebrotendinous xanthomatosis: Cytochrome 450; 2q33
  Charlevoix-Saguenay: Sacsin; 13q11
  Deafness: X-linked
  DRPLA: DRPLA protein; 12p13; Dominant
  Dystonias: DOPA-responsive
  Episodic ataxia: 1p; Dominant
  Evans
  Fitzsimmons syndrome
  Friedreich ataxia: FRDA; 9q13
  Hereditary Motor Syndromes
  HHH syndrome: SLC25A15; 13q14
  HMN + UMN signs: Senataxin; 9q34
  HMSN 5: Dominant
  HSN + Spastic paraparesis: CCT5; 5p15; Recessive
  Infantile spasms & Mental retardation: ARX; Xp22
  Infections: HTLV-1
  Krabbe: GalC; 14q31
  L1 cell adhesion molecule (MASA): Xq28
  Lawrence-Moon
  Leukodystrophy
    Child-onset: HSP60; 2q24; Recessive
    Adult-onset: Lamin B1; 5q31; Dominant
  Lipodystrophy & congenital cataracts: Dominant
  Mass lesions
  Mast syndrome (SPG 21)
  Mental retardation
    Psychosis & Macroorchidism: MECP2; Xq28
    Rett syndrome: MECP2; Xq28; Dominant
    Spasticity: MECP2; Xq28
    Small testes: ATRX; Xq13
    Strabismus
  Mitochondrial
  MLD: Arylsulfatase A; 22q13
  Myoclonic epilepsy
  Oculodentodigital dysplasia: GJA1; 6q22
  Paroxysmal Choreoathetosis/Spasticity: 1p; Dominant
  Phenylketonuria: 12q24
  Proteolipid protein: Xq21
  Retinal degeneration
  SCA3: ATX3; 14q32; Dominant
  Scheie: IDUA; 4p16
  Sensory ataxia: 8p12
  Silver syndromes: 11q12 & Other; Dominant
  Sjögren-Larsson: FALDH; 17p11
  SPAR: Dominant
  SPERM: Dominant
  Syringomyelia
  Woods-Black-Norbury Syndrome: Xq26; Dominant

Other spinal cord syndromes

Leukodystrophies
  Adrenomyeloneuropathy: ALDP; Xq28
  Adult-onset: Lamin B1; 5q31
  Krabbe: GalC; 14q31
  MLD: Arylsulfatase A; 22q13
Familial Spine disorders
  Achondroplasia: FGFR-3; 4p16
  Ankylosing spondylitis: 6p21
  Atlanto-Axial instability
  Cleidocranial dysplasia: RUNX2; 6p21
  Coffin-Lowry: RPS6KA3; Xp22
  Collagen, type II disorders
  Disc disease, Familial: Multiple loci
  Dyggve-Melchior-Clausen: FLJ90130; 18q21
  Larsen: Filamin B; 3p14
  Morquio syndromes
  Oculodentodigital dysplasia: GJA1; 6q22
  Opsismodysplasia
  Posterior longitudinal ligament: Ossification: 6p
  Pseudoachondroplastic dysplasia: COMP; 19p13
  Spondyloepiphyseal dysplasia variant
  Spondylometaepiphyseal dysplasia
  Spina bifida
  Tethered cord
  Trisomy 21

Spastic Ataxias
  Dominant
    Branchial myoclonus (Alexander): GFAP; 17q21
    DRPLA: DRPLA protein; 12p13.31
    Episodic ataxia + Choreoathetosis: 1p
    Lipodystrophy & Congenital cataracts
    Rett: MECP2 protein; Xq28
    SCA 3: Ataxin-3; 14q32
    SCA 7: Ataxin-7; 3p14
    Spastic ataxia 1 (SAX1): 12p13
    Spastic ataxia + congenital miosis
    Spastic ataxia ± Mental retardation (SPAR)
  Recessive
    Charlevoix-Saguenay: Sacsin; 13q11
    CLA2 Ataxia syndrome: X-linked
    Corneal dystrophy, Cataracts & Myopia
    DRPLA: Intermediate # CAG repeats
    Friedreich ataxia: Frataxin; 9q13-q21.1
    Karak syndrome
    Leukodystrophies
        Adrenomyeloneuropathy: ALDP; Xq28
        HLD6
        Krabbe: Galactosylceramide β-galactosidase; 14q31
        MLD: Arylsulfatase A; 22q13
    Leukoencephalopathy
        Ataxia, UMN signs & Neuropathy: RPIA; 2p11
        Vanishing white matter syndromes
        Brain stem & spinal cord + lactate elevation: DARS2; 1
    Marinesco-Sjögren: SIL1; 5q31
    Mental retardation & Osmiophilic skin vessels: 15q24
    Pelizaeus Merzbacher-like: GJA12; 1q41
    Portneuf: 2q33
    SAX2: 17p13
    SPG1: L1CAM; Xq28
    SPG2 (Pelizaeus Merzbacher): PLP; Xq21
    SPG30



SPG: General Principles11

Familial Spastic Paraplegia (Strumpell; FSP): Dominant

SPG3A: Atlastin; 14q11-q24
SPG4: Spastin; 2p24-p21
SPG6: NIPA1; 15q11.1
SPG8: KIAA0196; 8q23-q24
SPG9 (Cataracts & GI reflux): 10q23.3-q24.2
SPG10: KIF5A; 12q13
SPG12: 19q13
SPG13: HSPD1; 2q24
SPG17: 11q12
SPG19: 9q33
SPG29: 1p31
SPG31: REEP1; 2p12
SPG33: ZFYVE27; 10q24
SPG36: 12q23
SPG37: 8p21
SPG38: 4p16
SPG41: 11p14
Alzheimer (Presenilin 1): 14q24.3
HMSN 5
Multiple exostoses
SOX10: 22q13
Spastic ataxia


Familial Spastic Paraplegia (RFSP): Recessive

Cavanagh
Cerebrotendinous xanthomatosis
DRPLA: 12p13
Evans
Fitzsimmons syndrome
Friedreich ataxia: 9q13
Krabbe: 14q31
MLD: 22q13
Silver: 11q12
Sjögren-Larsson: 17p11.2
Spastic paraplegia + Myoclonic epilepsy
SPG 5: CYP7B1; 8q21
SPG 5B
SPG 7: Paraplegin; 16q24.3
SPG 11: 15q13
SPG 14: 3q27-q28
SPG 15: 14q
SPG 18: 8p12
SPG 20 (Troyer): Spartin; 13q12.3
SPG 21 (Mast): Maspardin; 15q22
SPG 24: 13q14
SPG 27: 10q22
SPG 30: 2q37
SPG 32: 14q12
SPG 39: PNPLA6; 19q13
SPG 45: 10q24.3
Infantile onset: Alsin; 2q33
SPOAN: 11q13
Symmetrical spastic cerebral palsy: 2q24-q25
Spastic ataxia
Spasticity + CNS
Spasticity + Ocular
Spasticity + PNS
Spasticity + Systemic Disorders


Cerebral palsy, Spastic Quadriplegic (CPSQ)

CPSQ1: GAD1; 2q31
CPSQ2: KANK1; 9p24
CPSQ3: AP4M1; 7q22

CPSQ1: Symmetrical spastic cerebral palsy
  l GAD1 ; Chromosome 2q31; Recessive CPSQ2
  l KN motif and ankyrin repeat domains 1 (ANKRD15; KANK1) ; Chromosome 9p24.3; Recessive with parental effect CPSQ3
  l Adaptor-related protein complex 4, Mu-1 SUBUNIT (AP4M1; MU-ARP2) ; Chromosome 7q22.1; Recessive
Familial Spastic Paraplegia: X-linked

Adrenomyeloneuropathy: ALDP; Xq28
Mental retardation
  Infantile spasms: ARX; Xp22
  Psychosis, & Macroorchidism: Xq28
  Rett syndrome: MECP2; Xq28
  Small testes: ATRX; Xq13
  SPG1: L1CAM; Xq28
  SPG2: PLP; Xq21
  Strabismus: X
Woods-Black-Norbury Syndrome: Xq26
SPG 16: Xq11
SPG 34: Xq25


Syringomyelia
Cleidocranial dysplasia


from A Kornberg MD







Familial Spine Disorders & Myelopathy

Achondroplasia
Ankylosing spondylitis
Atlanto-Axial dislocation
Cleidocranial dysplasia
Coffin-Lowry
Collagen, type II disorders
Disk disease
Dyggve-Melchior-Clausen
Hypophosphatemia; Rickets
Larsen
Lumbar stenosis
Morquio
Oculodentodigital Dysplasia
Opsismodysplasia
Posterior longitudinal ligament
  Ossification
  Thickening
Pseudoachondroplastic dysplasia
Spondyloepiphyseal dysplasia variant
Spondylometaepiphyseal dysplasia
Spina bifida
Spinal Stenosis
Tethered cord
Trisomy 21
Also see:
  Acquired systemic causes of spine disorders
  Aggrecan mouse
  Radiology: Spine; Cervical spine




  • Hypophosphatemia, Vitamin D resistant rickets

  • Aggrecan heterozygosity: Mouse model
    Arnold-Chiari Malformation
      l Autosomal recessive or sporadic
      l With syringomyelia
    Spastic Ataxia Syndromes: Dominant or Recessive

    Hereditary Spastic Ataxia (SAX1) 21
      l Chromosome 12p13; Dominant


  • Spastic ataxia (SAX2) 62
      l Chromosome 17p13; Recessive

    Branchial myoclonus with Spastic paraparesis & Cerebellar ataxia
      l Glial fibrillary acidic protein (GFAP) ; Chromosome 17q21; Dominant
    Spastic ataxia, congenital, with Mental retardation & Osmiophilic skin vessels (CAMOS; SCAR5)18
      l Chromosome 15q24-q26; Recessive
    Spastic Paraplegia, Ataxia ± Mental Retardation (SPAR) 23
      l Autosomal Dominant
    Spastic Paraplegia, Epilepsy & Mental Retardation (SPERM)
      l Autosomal Dominant
    Lipodystrophy with Spastic-Ataxia & Congenital cataracts 25
      l Autosomal Dominant
    Paroxysmal Choreoathetosis/Spasticity (CSE; DYT9)
      l Chromosome 1p; Dominant

    Hypomyelinating Leukodystrophy 6 (HLD6; HABC)
      l Sporadic, ? Recessive

    Leukoencephalopathy with Ataxia, UMN signs & Polyneuropathy44
      l Ribose-5-Phosphate Isomerase (RPIA) ; Chromosome 2p11.2; Recessive

    Pelizaeus-Merzbacher–Like Disease (PMLD; HLD2) 46
      l Gap Junction Protein α12 (Connexin 46.6; GJA12) ; Chromosome 1q41-q42; Recessive


    Hereditary Sensory Ataxia (SNAX1; ADSA) 48
      l Chromosome 8p12.1-8q11.23; Dominant


    Spastic dystonia syndromes
    Mass lesions
    Other familial spinal syndromes
    Differential diagnosis of hereditary spastic paraplegia
    Category Disorders
    Structural abnormality Spinal: Spondylosis; Atlanto-axial; Canal stenosis
    Vascular: Arteriovenous malformation
    Congenital: Arnold-Chiari; Tethered cord
    Mass: Neoplasm; Granuloma; Syringomyelia
    Degenerative disorders Multiple sclerosis; Amyotrophic lateral sclerosis; Spinocerebellar ataxias
    Leukodystrophies Adrenomyeloneuropathy; Krabbe; Metachromatic leukodystrophy
    Metabolic disorders Vitamin deficiency: B12; E; Abetalipoproteinemia; Mitochondrial disorders
    Infections Syphilis; HTLV; HIV (AIDS); Lyme
    Other DOPA-responsive dystonia; Hydrocephalus; Toxins

    Return to Spinal Cord Index
    Return to Neuromuscular home page

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