Sex Differences in Dystonia

Abstract

Background: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms.

Objectives: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences.

Methods: Data from individuals with various types of dystonia were analyzed in relation to sex. Data came from two different sources. One source was the Dystonia Coalition database, which contains predominantly idiopathic adult-onset focal and segmental dystonias. The second source was the MDSGene database, which contains predominantly early-onset monogenic dystonias.

Results: The 3222 individuals from the Dystonia Coalition included 71% female participants and 29% male participants for an overall female-to-male ratio (F:M) of 2.4. This ratio varied according to body region affected and whether dystonia was task-specific. The female predominance was age-dependent. Sex did not have a significant impact on co-existing tremor, geste antagoniste, depression or anxiety. In the 1377 individuals from the MDSGene database, female participants outnumbered male participants for some genes (GNAL, GCH1, and ANO3) but not for other genes (THAP1, TH, and TOR1A).

Conclusions: These results are in keeping with prior studies that have indicated female individuals outnumber male individuals for both adult-onset idiopathic and early onset monogenic dystonias. These results extend prior observations by revealing that sex ratios depend on the type of dystonia, age, and underlying genetics.

Keywords: blepharospasm; dystonia; sex differences; spasmodic dysphonia; writer's cramp.

Figure 1

Sex distributions in the Dystonia Coalition database. Results show female to male (F:M) ratios, with the total number of cases noted at the top of each bar. Panel A shows dystonias according to diagnostic groups defined by the distribution of body regions affected for the whole group. Panel B shows F:M ratios according to specific body regions affected also for the whole group, regardless of other regions simultaneously affected.

Figure 2

Sex distributions among task‐specific dystonias. Panel A shows the female to male (F:M) ratios for writer's cramp (WC), the most common task‐specific dystonia, in the published literature. Panel B shows the F:M ratios for all task‐specific dystonias in the Dystonia Coalition cohort. The numbers at the top of the bars indicate the total number of cases evaluated. (B) cases of speech‐related dystonia that were simultaneously designated as task‐specific (n = 203), and includes mostly laryngeal dystonias but also some oromandibular dystonia. Fig. 1B shows all cases of laryngeal dystonia, whether or not they were designated as task‐specific.

Figure 3

Severity of dystonia according to sex. The bars show the average scores from the Global Dystonia Rating Scale (GDRS) according to body region affected (±SEM). Males are shown in black, while females are shown in gray. ANOVA revealed highly significant effects for sex (F = 35.5, P < 10⁻⁸) and body region (F = 57.5, P < 10⁻¹⁵) but no interaction between sex and body region.

Figure 4

Sex and age at onset in the Dystonia Coalition cohort. Panel A shows F:M ratio according to decade of life, with the total number of cases at the top of each bar. Panel B shows cumulative counts of female or male cases according to year of age. Panel C shows percentage of females (gray bars) and males (black bars) relative to sex hormone changes (T = testosterone; E = estrogen) of aging (dotted lines). The lines were estimated from relative hormone levels in prior reports. **p < 0.01.

Figure 5

Sex and monogenic dystonias. Panel A shows the overall percentage of females according to gene, with the total number of cases at the top of the bar. The asterixis indicate significant differences in sex distributions. Panel B shows the total numbers of female (gray bars) or male (black bars) individuals according to age groups for selected monogenic dystonias where there were sufficient numbers for meaningful analyses.