Hand stereotypies: Lessons from the Rett Syndrome Natural History Study

Abstract

Objective: To characterize hand stereotypies (HS) in a large cohort of participants with Rett syndrome (RTT).

Methods: Data from 1,123 girls and women enrolled in the RTT Natural History Study were gathered. Standard tests for continuous and categorical variables were used at baseline. For longitudinal data, we used repeated-measures linear and logistic regression models and nonparametric tests.

Results: HS were reported in 922 participants with classic RTT (100%), 73 with atypical severe RTT (97.3%), 74 with atypical mild RTT (96.1%), and 17 females with MECP2 mutations without RTT (34.7%). Individuals with RTT who had classic presentation or severe MECP2 mutations had higher frequency and earlier onset of HS. Heterogeneity of HS types was confirmed, but variety decreased over time. At baseline, almost half of the participants with RTT had hand mouthing, which like clapping/tapping, decreased over time. These 2 HS types were more frequently reported than wringing/washing. Increased HS severity (prevalence and frequency) was associated with worsened measures of hand function. Number and type of HS were not related to hand function. Overall clinical severity was worse with decreased hand function but only weakly related to any HS characteristic. While hand function decreased over time, prevalence and frequency of HS remained relatively unchanged and high.

Conclusions: Nearly all individuals with RTT have severe and multiple types of HS, with mouthing and clapping/tapping decreasing over time. Interaction between HS frequency and hand function is complex. Understanding the natural history of HS in RTT could assist in clinical care and evaluation of new interventions.

Figure 1. Flow diagram of the study

Study population and description of groups enrolled in the Rett Syndrome Natural History Study. MECP2 = methyl-CpG binding protein 2; RTT = Rett syndrome.

Figure 2. Hand stereotypy frequency scores (percent of time observed by clinician) based on diagnosis group

HS = hand stereotypy; MECP2 = gene coding the methyl-CpG binding protein 2; RTT = Rett syndrome.

Figure 3. Hand stereotypies types in Rett syndrome

(A) Based on diagnosis group. (B) Based on age group. Note: “mouthing” includes participants with either or both “mouthing right” and “mouthing left.” Somers D, **p < 0.01, ***p < 0.001. HS = hand stereotypy; RTT = Rett syndrome.

Figure 4. Longitudinal changes in prevalence of the most common types of hand stereotypies in Rett syndrome

(A) Logistic regression models' prediction of the 3 most common types of hand stereotypies. Note: significance of factors in logistic regression model for mouthing: visit (p < 0.001), age at assessment (p < 0.001), visit x age at assessment (p < 0.001); clapping/tapping: visit (NS), age at assessment (p < 0.001), visit x age at assessment (NS); wringing/washing: visit (p < 0.01), age at assessment (NS), visit x age at assessment (p < 0.05). (B) Dynamics of hand mouthing. Participants were stratified into 2 cohorts at baseline: pediatric participants younger than 21 years (n = 812) and adult participants 21 years and older (n = 109). Change per McNemar test from baseline: *p < 0.05, **p < 0.01, ***p < 0.001. Change per McNemar test from previous year: #p < 0.05. NS = not significant.