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CONTRACTURES & OTHER JOINT DISORDERS

Contractures + Neuromuscular disorders
Arthrogryposis
  Myopathy
  Distal
Bethlem Myopathy
Congenital muscular dystrophy
Dermatomyositis
Dystrophinopathies
Ehlers-Danlos (EDSMC): 1; 2
Emery-Dreifuss
Fasciitis
Hereditary IBM + Ophthalmoplegia 
IM drug injections
Lethal congenital (LCCS)
Nemaline (Rod) myopathy: Severe
Rigid spine syndromes
Scleroatonic muscular dystrophy (Ullrich)
Spinal Muscular Atrophy
  5q-linked Congenital
  X-linked Infantile
Tel Hashomer camptodactyly
Williams-Beuren syndrome
Joint Hyperlaxity
Ullrich CMD
CMD + Joint hyperlaxity
Mental retardation

Contractures with myopathy or other neuromuscular disease





Emery-Dreifuss Muscular Dystrophy 2


EMD1: Emerin; Xq28; Recessive
EMD2: Lamin A/C; 1q21.2; Dominant
EMD3: Lamin A/C; 1q21.2; Recessive
EMD4: SYNE1; 6q25; Dominant
EMD5: SYNE2; 14q23; Dominant
EMD6: FHL1; Xq26; Recessive or Semi-Dominant
EMD7; TMEM43; 3p25; Dominant
Other: Sporadic & Dominant

from A Kornberg MD

Emery-Dreifuss MD 1 (EMD1; EDMD1)
  Emerin ; Chromosome Xq28; Recessive


Emery-Dreifuss MD 2 & 3
  Lamin A/C ; Chromosome 1q22; Dominant (EMD2) or Recessive (EMD3)


Emery-Dreifuss MD 4 (EMD4; EDMD4) 20
  Synaptic nuclear envelope protein 1 (SYNE1; Nesprin-1) ; Chromosome 6q25.1-q25.2; Dominant

Emery-Dreifuss MD 5 (EMD5; EDMD5) 20
  Synaptic nuclear envelope protein 2 (SYNE2; Nesprin-2) ; Chromosome 14q23.2; Dominant

Emery-Dreifuss MD 7 (EMD7; EDMD7) 24
  Transmembrane protein 43 (TMEM43; LUMA) ; Chromosome 3p25.1; Dominant

Nuclear Protein Disorders: Envelope & Matrix



Arthrogryposis multiplex congenita (AMC) 29

General aspects
  Clinical features
  Associated disorders & syndromes
  Treatment & prognosis
    Neurogenic
Syndromes with Myopathy

Syndromes without general Myopathy
  Recessive
    Arthropathy-Camptodactyly: PRG4
    Cerebellar & Pancreatic Aplasia: PTF1A
    COFS: ERCC6
    Distal arthrogryposis
      5D: ECEL1; 2q37
    Ectodermal dysplasia
    Jarcho-Levin: DLL3
    Lethal congenital contractures (LCCS)
    Lethal congenital myopathy: CNTN1
    Lissencephaly
    Mental retardation & Seizures: SLC35A3
    Multiple pterygium (Escobar)
    Neurogenic
    Pelvic hypoplasia
    Pulmonary hypoplasia
    Renal dysfunction
    Spinal muscular atrophy (SMA)
      5q-linked Congenital: SMN1
      SMA + Pontocerebellar hypoplasia
        PCH1A: VRK1
        PCH1B: EXOSC3
      Congenital non-progressive: TRPV4
    Spondylospinal Thoracic dysostosis
    Emery-Dreifuss MD 4: SYNE1

  X-linked
    Aarskog–Scott: FGD1
    Infantile SMA + Arthrogryposis: UBE1
    Intellectual disability & Weak: ZC4H2
  Dominant
    Clubfoot, asymmetric
    Contractural arachnodactyly (DA9): FBN2
    Distal arthrogryposis: Types
        1A: TPM2
        1B: MYBPC1
        1 Other
        2A: TPM3
        2B: TNNI2; TNNT3; MYH3; TPM2
        3 (Gordon): PIEZO2; 18p11
        5A: MYH2; 17p13
        5B: MYH13; 17p13
        5C: 11
        5E: PIEZO2; 18p11
        6: FGFR3; 4p16
        7: MYH8; 17p13
        9: FBN2; 5q23
        10: 2q
        4; 5; 8
        Cardiac myxomas: MYH8; 17p13
        HSAN 6: DST
        Rienhoff: TGFB3; 14q24
    Möbius Syndrome
    Oculomotor abnormalities (DA5)
    Saethre-Chotzen syndrome: TWIST

  Mitochondrial
  Neuropathy
    AR-CMT
  Sporadic
    Amyoplasia
    Neurogenic
    Trisomy 18
Fetal Akinesia Syndromes: Genes
  Motor neuron development & survival
    SMN1 (SMA)
    GLE1 (LCCS1)
    ERBB3 (LCCS2)
    PIP5K1C (LCCS3)
    UBE1 (SMAX2)
  Neuronal
    ECEL1
    PIEZO2
  Neuromuscular junction components
    CHRNA1
    CHRND
    CHRNG
    CNTN1
    DOK7
    RAPSN
    ZC4H2
  Skeletal muscle proteins
    ACTA1
    BIN1
    FKRP
    KLHL41
    MTM1
    MYH2
    MYH3
    MYH8
    MYBPC1 (LCCS4)
    NEB
    RYR1
    TPM2
    TNNI2
    TNNT3
  Nuclear proteins
    LMNA
    SYNE1
  Other genes
    DMPK
    FGFR2
    GBE1

Arthrogryposis: General
Arthrogryposis: Clinical features
  • Contractures
    • Often symmetric involvement of 4 limbs
    • Distal > Proximal
    • Flexion posture ± Joint dislocation
    • Elbows > Knees > Feet > Hips > Hands > Shoulders
    • Camptodactyly: Flexion deformity at proximal interphalangeal joints
  • Limbs
    • Shape: Often fusiform or cylindrical
    • Length: Mildly short
  • Skin (At joints)
    • Absent creases
    • Dimpling ± Webbing
    • Pterygia or Webs
      • Early & sustained lack of movement in utero
      • Onset > 8 weeks: After joint formation
  • Skeletal
    • Micrognathia
    • Palate: High arched or Cleft
    • Scoliosis
    • Long bones: Osteoporosis
  • Systems
    • Renal + Cholestasis
      • ARCS1 : VPS33B ; 15q26.1
      • ARCS2 : VIPAR ; 14q24.3
    • Cardiac defects
    • Pulmonary hypoplasia : RAPSYN ; 11p11.2
    • CNS
    • Ectodermal dysplasia
    • GI: Short or immature gut
  • Polyhydramnios: Later in pregnancy
  • Prognosis
    • Improvement over time with
      • Early physiotherapy
      • Orthopedic care
    • Worst with CNS involvement: 50% death in infancy
    • Best: Amyoplasia
  • Treatment
    • Physical therapy: To achieve
      • Lower limbs: Weight bearing joints
      • Upper limbs: Maximum functionality
    • Surgery: Reduce contractures
   
Camptodactyly

Arthrogryposis: Associated disorders Distal arthrogryposes Arthrogryposis Syndromes 1


Aarskog–Scott syndrome 25
  FYVE, RhoGEF and PH Domain-containing protein 1 (FGD1) ; Chromosome Xp11.22; Recessive

Arthrogryposis Multiplex Congenita & Intellectual Disability 27
  Zinc finger C4H2 domain-containing protein (ZC4H2) ; Chromosome Xq11.2; Semi-Dominant
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References

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3. Eur J Ped Neurol 2001;5:3-5
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24. Ann Neurol 2010; Online November
25. Clinical Dysmorphology 2013;22:13-17
26. Am J Hum Genet 2012; Online Dec
27. Am J Hum Genet 2013;92:681-695
28. Hum Mol Genet 2013 Dec 6
29. European Journal of Medical Genetics 2014; Online April
30. Hum Mol Genet. 2014 Jul 23

10/23/2014