Urologic and gastrointestinal symptoms in the dystroglycanopathies

Abstract

Objective: To determine the frequency of urologic and gastrointestinal (GI) symptoms in a cohort of individuals with dystroglycanopathy compared with healthy household controls.

Methods: Participants in a North American dystroglycanopathy natural history study (NCT00313677) and other members of their households completed a questionnaire modified from validated instruments and clinical criteria. Urologic and GI symptom frequency, effect on patient life, and medications taken for these symptoms were assessed. Those younger than 4 years or not toilet trained were excluded. Healthy human bladder, esophagus, and duodenum from surgical specimens were immunostained for glycosylated α-dystroglycan.

Results: Thirty of 58 potential participants with dystroglycanopathy (51.7%) and 16 household controls participated. Subjects were aged 6 to 51 years (mean 26.7); 60.0% were female. Controls were aged 7 to 55 years (mean 34.6); 56.3% were female. The dystroglycanopathy cohort had higher frequency of urinary voiding symptoms (p = 0.02), higher urologic symptom scores (p = 0.05), and higher dysphagia symptom scores (p = 0.04). A correlation existed between urologic symptom score and effect on life (r = 0.71; 95% confidence interval 0.46, 0.85; p < 0.0001) and between dysphagia symptom score and effect on life (r = 0.72; 95% confidence interval 0.48, 0.86; p < 0.0001). Glycosylated α-dystroglycan was present in visceral smooth muscle of all normal tissues analyzed.

Conclusions: Urologic symptoms and dysphagia are reported more frequently by individuals with dystroglycanopathies than by household controls. These symptoms can cause a perceived negative effect on patient life. Our results suggest urologic and GI dysfunction may be part of the dystroglycanopathy phenotype, and that questions about these symptoms should be incorporated into routine care because they may influence medical management.

© 2015 American Academy of Neurology.

Figures

Figure 1. Urologic symptoms in dystroglycanopathy (DG) relative to household controls

Participants responded to individual questionnaire items on urinary hesitancy (A), double voiding (B), and urinary intermittency or weak stream (C). Responses to questions on individual symptoms were scored and summed to obtain overall urologic symptom score (D). Individual symptoms were grouped physiologically into categories including voiding (E) and postmicturition (F) symptoms.

Figure 2. Perceived effect of urologic symptoms and dysphagia on the life of patients with dystroglycanopathy

Participant response to question regarding perceived effect on participant life of urologic symptoms was compared against calculated urologic symptom score (A). Participant response to item on perceived effect on participant life exerted by swallowing symptoms was compared against calculated dysphagia symptom score (B). CI = confidence interval.

Figure 3. Gastrointestinal symptoms in dystroglycanopathy (DG) relative to household controls

Participants provided their level of agreement with questionnaire item on dysphagia to solids (A). Responses to individual questions relating to dysphagia were scored and summed to obtain overall dysphagia symptom score (B).

Figure 4. Immunofluorescence studies

Components of the dystrophin-glycoprotein complex are expressed in skeletal muscle (A, C, and E) and visceral smooth muscle, duodenum presented here (B, D, and F). Shown are α-dystroglycan (A and B), β-dystroglycan (C and D), and dystrophin (E and F). The scale bar is 120 µm in A, C, and E, 60 µm in B, D, and F.