TY  - CHAP
M1  - Book, Section
TI  - Spinocerebellar Ataxias
A1  - Zoghbi, Huda Y.
A1  - Orr, Harry T.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
PY  - 2019
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - The  dominantly  inherited  spinocerebellar  ataxias  (SCAs)  are  a  heterogeneous  group  of  neurologic  disorders  characterized  by  variable  degrees  of  degeneration  of  the  cerebellum,  spinocerebellar  tracts,  and  brain  stem  neurons.  The  inter-  and  intrafamilial  variability  of  clinicopathologic  findings  hampered  the  classification  of  this  group  of  diseases  until  the  1990s,  during  which  the  discovery  of  the  genetic  bases  of  many  of  the  SCAs  provided  a  means  of  distinguishing  among  them.The  mutational  locus  has  been  mapped  for  10  SCAs:  spinocerebellar  ataxia  1,  2,  etc.  [disease  in  Roman  font  and  gene  in  italics]  (SCA1,  SCA2),  Machado-Joseph  disease  (MJD)/SCA3  (sometimes  referred  to  here  simply  as  SCA3),  SCA4,  SCA5,  SCA6,  SCA7,  SCA8,  SCA10,  and  dentatorubropallidoluysian  atrophy  (DRPLA).  The  clinical  features  shared  among  these  SCAs  are  ataxia,  dysarthria,  and  eventual  bulbar  dysfunction.  Variable  features  include  ophthalmoparesis  (common  in  SCA1,  2,  3,  and  7);  hyporeflexia  (common  in  SCA2  and  4);  dementia  (more  frequent  in  SCA2  and  common  in  DRPLA);  dystonia  and  rigidity  (occasional  in  SCA1  and  common  in  MJD/SCA3);  choreoathetosis  and  myoclonus  (common  in  DRPLA);  spasticity  (SCA1,  3,  and  DRPLA);  bulging  eyes  and  fasciculations  (MJD/SCA3);  neuropathy  (most  common  in  SCA4  but  can  be  seen  in  SCA1,  2,  and  3);  seizures  (common  in  SCA10  and  DRPLA);  and  macular  degeneration  and  extraneuronal  involvement  (unique  to  SCA7).  Neuroimaging  studies  demonstrate  cerebellar  atrophy  in  SCA1,  2,  3,  6,  7,  and  DRPLA;  cortical  atrophy  in  SCA2,  7,  and  DRPLA;  and  brain  stem  atrophy  in  SCA1,  2,  3,  7,  and  DRPLA.  Calcification  of  the  basal  ganglia  and  leukodystrophic  changes  occur  in  DRPLA.  Nerve  conduction  abnormalities  occur  in  SCA1,  2,  and  3,  and  are  most  common  in  SCA4.  Visual  evoked  potentials  are  abnormal  in  SCA7,  and  the  EEG  is  abnormal  in  DRPLA.  Purkinje  cell  and  dentate  neuron  degeneration  is  severe  in  SCA1,  2,  6,  7,  and  DRPLA,  but  modest  in  MJD/SCA3.  Degeneration  of  the  inferior  olive  is  common  in  SCA1,  2,  6,  and  7.  Loss  of  brain  stem  neurons  is  common  in  SCA1,  2,  3,  6,  and  DRPLA.  Basal  ganglia  degeneration  is  pronounced  in  DRPLA  and  variable  in  MJD/SCA3.  Macular  degeneration  and  hypomyelination  of  the  optic  tract  are  unique  to  SCA7.The  mutational  basis  of  SCA1,  SCA2,  MJD/SCA3,  SCA6,  SCA7,  and  DRPLA  is  the  expansion  of  a  translated  trinucleotide  (CAG)  repeat  that  encodes  for  a  polyglutamine  tract  in  the  relevant  protein.  SCA8  is  caused  by  expansion  of  a  CTA/CTG  repeat  that  does  not  appear  to  be  translated.  Expanded  disease  alleles  typically  contain  34  to  84  CAG  repeats  in  SCA1,  2,  3,  and  DRPLA.  In  SCA6,  the  pathogenic  range  is  21  to  33,  and  in  SCA7  it  is  35  to  306.  For  SCA8  the  expanded  range  varies  from  110  to  130  in  kindreds  with  established  linkage  to  the  SCA8  locus,  but  has  been  found  to  exceed  575  repeats  in  some  affected  patients.The  gene  products  mutated  in  most  of  the  SCAs—ataxin-1,  ataxin-2,  ataxin-3,  ataxin-7,  and  atrophin-1—are  novel  proteins  of  unknown  function.  The  gene  product  mutated  in  SCA6  is  the  α1A  voltage-gated  calcium  channel  (CACN1A1).  The  distribution  of  the  proteins  varies:  ataxin-1  is  predominantly  nuclear  in  neurons,  but  cytoplasmic  in  peripheral  cells.  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - ommbid.mhmedical.com/content.aspx?aid=1181479002
ER  -