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.