title: The Incidence and Evolution of Parkinsonian Rigidity in Rett Syndrome: A Pilot Study.
abstract: BACKGROUND
  Patients with Rett syndrome (RTT) may demonstrate parkinsonian features. Here, we report a preliminary cross-sectional and prospective evaluation of the evolution, regional distribution, and eventual incidence of rigid tone in a cohort of MECP2 mutation-positive patients.
  
  
  METHODS
  In 51 participants, muscle tone rigidity in extremity regions and neck plus hypomimia were quantified using an RTT rigidity distribution (RTTRD) score with a range of 0 to 15. RTTRD scores were correlated with age, ability to walk and speak, mutation type, and, in a small subgroup (n=9), cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid levels.
  
  
  RESULTS
  Participant ages ranged from 2 years and 5 months, to 54 years. Rigidity was found in 43/51 (84.3%); it appeared as early as age 3, increased in extent with age, and was present in all participants aged ≥13. Ankle region rigidity appeared first, followed by proximal legs, arms, neck, and face. Ambulatory participants (n=21) had lower RTTRD scores than nonambulatory (n=30; p=0.003). We found a trend to lower scores in participants with retained speech (n=13) versus those with none (n=38; p=0.074), and no difference in scores for those with truncating (n=25) versus missense mutations (n=22; p=0.387). RTTRD scores correlated negatively with CSF HVA levels (R=-0.83; p=0.005), but not with 5-hydroxyindole-acetic acid levels (R=-0.45; p=0.22).
  
  
  CONCLUSIONS
  Although assessment of muscle tone is somewhat subjective and the RTTRD has not been validated, this study nevertheless suggests that parkinsonian rigidity in RTT is common and frequently increases in extent with age; its severity correlates directly with impaired ambulation and inversely with CSF HVA levels.
authors.affiliation: 1Department of Paediatrics,Division of Neurology,Children's Hospital of Eastern Ontario,Ottawa,Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Humphreys
authors.affiliation: 2Research Institute,Children's Hospital of Eastern Ontario,Ottawa,Canada.
authors.forename: Nick
authors.initials: N
authors.lastname: Barrowman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D007211:Indoles / Q000134:cerebrospinal fluid; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D008875:Middle Aged; D009127:Muscle Rigidity / Q000209:etiology* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D020734:Parkinsonian Disorders / Q000453:epidemiology* / Q000209:etiology*; D010865:Pilot Projects; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000134:cerebrospinal fluid / Q000150:complications* / Q000453:epidemiology* / Q000235:genetics; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D007211:Indoles; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; C024139:indole-3-lactic acid; D006719:Homovanillic Acid
keywords: Dopamine; HVA; MECP2; Rett syndrome; dystonia; parkinsonism