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

Table 3 Overview of each type of genetic myopathy, including prevalence rates, age, sex, genetic bases, key clinical features, diagnostic approaches, and management strategies

Type of myopathy	Prevalence	Age of onset	Sex	Most affected races	Genetic basis	Key clinical features	Diagnostic approaches	Management strategies
DMD	1 in 3500 to 1 in 9300 male births globally	Early childhood	Males	All races, more common in certain populations such as Caucasian and African American	X-linked recessive genetic disorder caused by mutations in the dystrophin gene located on the X chromosome. Mutations include deletions, duplications, and point mutations	Muscle weakness, delayed motor milestones, dysphagia, GERD, delayed gastric emptying, constipation, pseudo-obstruction	Magnetic resonance imaging for smooth muscle atrophy, gastric emptying scintigraphy, genetic testing for dystrophin mutations	Swallowing therapy, proton pump inhibitors, dietary modifications, fundoplication for severe GERD
Becker muscular dystrophy	1–6 per 100000 individuals	Adolescence or early adulthood	Males	All races, more common in certain populations such as Caucasian and African American	Milder allelic form of DMD, also caused by mutations in the dystrophin gene, typically in-frame deletions, duplications, or small insertions, allowing some functional dystrophin protein to be produced	Similar to DMD but milder and later onset; dysphagia, GERD, delayed gastric emptying, fatty liver disease	Upper GI series, abdominal ultrasound for hepatomegaly, genetic testing	Nutritional support, laxatives for constipation, hepatoprotective agents
LGMD	1 in 14500–123000 globally	Varies (typically adolescence or adulthood)	Both sexes	All races	A heterogeneous group of disorders categorized into autosomal dominant (LGMD1) and autosomal recessive (LGMD2) forms involving mutations in various genes such as Lamin A/C, Calpain 3, and Dysferlin. Over 50 genetic loci were identified as potential contributors	Weakness in shoulder and pelvic girdle muscles, dysphagia, constipation, elevated liver enzymes	Esophageal manometry, liver ultrasound	Dietary fiber, biofeedback therapy for bowel dysfunction
Congenital myopathies	1.62 per 100000 globally (higher in children)	Present at birth or infancy	Both sexes have a higher prevalence in children	All races	A diverse group of disorders present at birth or infancy, caused by mutations in over 40 genes with various inheritance patterns, including ACTA1, RYR1, and Dynamin 2	Muscle hypotonia, delayed motor milestones, feeding difficulties, dysphagia, GERD, constipation, recurrent respiratory infections	Muscle biopsy, barium swallow, upper GI endoscopy	Feeding therapy, nutritional support, reflux management, respiratory care
Metabolic myopathies	1 in 5000 to 1 in 50000 individuals	Varies (childhood or adulthood)	Both sexes	All races	Caused by gene mutations affecting carbohydrate or fat metabolism within muscle cells, leading to disorders such as McArdle disease (PYGM gene) and Tarui disease (PFKM gene)	Exercise intolerance, muscle cramps, recurrent abdominal pain, nausea, diarrhea, fatty liver, hypoglycemia, hepatomegaly	Genetic panels, metabolic tests (e.g., carnitine palmitoyltransferase or very long-chain acyl-CoA dehydrogenase), gastric motility studies	Dietary adjustments, enzyme replacement (e.g., pancreatic enzymes), glucose infusions for hypoglycemia
Mitochondrial myopathies	1 in 5000 to 1 in 10000	Varies (childhood or adulthood)	Both sexes	All races	Result from mutations in genes involved in mitochondrial function and energy production, including MT-TL1 (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome), MT-TK (myoclonic epilepsy with ragged red fibers syndrome), and sea urchin retroposon family 1 (Leigh syndrome). Inheritance can be autosomal recessive or matrilineal (mitochondrial DNA mutations)	Dysphagia, diarrhea, gastroparesis, pancreatitis, pseudo-obstruction, hepatopathy, malabsorption	Muscle biopsy, genetic testing for mitochondrial DNA mutations, gastric motility studies	Prokinetic agents, pancreatic enzyme replacement, nutritional supplementation
Myotonic disorders	1 in 8000 to 1 in 20000 globally	Typically adulthood	Both sexes	All races	This includes DM Type 1 (DM1) and Type 2 (DM2), caused by expanded CTG repeats in the DMPK gene and CCTG repeats in the ZNFN213 gene, respectively. Autosomal dominant inheritance pattern	Dysphagia, GERD, constipation, paralytic ileus, diarrhea, megacolon, sigmoid volvulus, anal incontinence	Radiologic studies for motility, manometry, genetic testing for DMPK and ZNFN213 genes	Swallowing therapy, dietary modifications, management of motility disorders, surgical interventions for volvulus or megacolon

DM: Myotonic dystrophy; DMD: Duchenne muscular dystrophy; DMPK: Dystrophia myotonica protein kinase; GERD: Gastroesophageal reflux disease; GI: Gastrointestinal; LGMD: Limb-girdle muscular dystrophy.