Navigating gastrointestinal challenges in genetic myopathies: Diagnostic insights and future directions

Table 6 Genetic and environmental modifiers of gastrointestinal symptoms in genetic myopathies

Modifier type	Key influences	Impact on GI symptoms	Clinical implications
Genetic modifiers	Modifier genes (e.g., laminin alpha 2-chain gene, Lamin A/C, Calpain 3, Dysferlin)	Alters smooth muscle integrity and neuromuscular transmission in the gut	Genetic screening may help predict GI severity and guide therapy
	MtDNA mutations (mtDNA heteroplasmy)	Variable energy deficits affecting intestinal motility and absorption	Mitochondrial-targeted therapies and dietary modifications
	Epigenetic changes (DNA methylation, histone modifications)	May regulate neuromuscular gene expression, impacting gut function	Potential target for gene modulation therapy
Gut microbiota	Dysbiosis (loss of beneficial bacteria, increase in pathogenic bacteria)	Worsens constipation, diarrhea, bloating, and inflammation	Probiotics, microbiome-targeted interventions (e.g., fecal microbiota transplantation)
Nutritional status	Protein intake, fiber intake, vitamin deficiencies (e.g., B12, D, Mg)	Deficiencies impair gut motility and neuromuscular coordination	Tailored dietary interventions, vitamin supplementation
Mobility status	Reduced physical activity due to progressive muscle weakness	Slows intestinal transit, leading to severe constipation and GERD	Early physiotherapy and bowel training programs
Medications	Corticosteroids (e.g., used in Duchenne muscular dystrophy), opioids, anticonvulsants	GERD, delayed gastric emptying, constipation	Medication adjustments and use of gut motility agents
Environmental and psychosocial factors	Stress, anxiety, healthcare access disparities	Can worsen functional gut disorders (e.g., IBS-like symptoms in myopathies)	Psychological support and patient education

GERD: Gastroesophageal reflux disease; GI: Gastrointestinal; MtDNA: Mitochondrial DNA.