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

Table 1 Summary of studies on gastrointestinal disorders in genetic myopathies

Ref.	Study title	Population	GI manifestations	Methods	Key findings
Jaffe et al[15], 1990	Symptoms of upper gastrointestinal dysfunction in Duchenne muscular dystrophy: Case-control study	55 DMD patients, 55 controls	Dysphagia, choking, heartburn, vomiting	Case-control study, questionnaire-based assessment	DMD patients had significantly more GI symptoms than controls, especially oropharyngeal dysfunction
Lo Cascio et al[18], 2016	Gastrointestinal Dysfunction in Patients with Duchenne Muscular Dystrophy	33 DMD patients (12-41 years)	Constipation, delayed gastric emptying, prolonged oro-cecal transit time	Questionnaires, gastric emptying time, colonic transit studies	DMD patients had prolonged gastric emptying and colonic transit times, indicating severe GI dysmotility
Lee et al[23], 2020	Relationship between Eating and Digestive Symptoms and Respiratory Function in Advanced Duchenne Muscular Dystrophy Patients	180 advanced DMD patients	Constipation, swallowing difficulty, aspiration	Questionnaires, respiratory function tests	GI symptoms correlated with respiratory function, not age, indicating progressive neuromuscular decline
Borrelli et al[24], 2005	Evolution of gastric electrical features and gastric emptying in children with Duchenne and Becker muscular dystrophy	20 children with DMD/BMD	Delayed gastric emptying, dysrhythmias	Electrogastrography, ultrasonography	DMD patients showed worsening gastric motility over time, BMD patients had milder symptoms
Kansu et al[21], 2023	The frequency of Duchenne muscular dystrophy/Becker muscular dystrophy and Pompe disease in children with isolated transaminase elevation: results from the observational VICTORIA study	589 children with elevated transaminases	Liver dysfunction, metabolic abnormalities	CPK testing, genetic analysis	DMD/BMD diagnosed in 47% of male patients with isolated hypertransaminasemia
Tang et al[22], 2022	Hepatic Steatosis Assessment as a New Strategy for the Metabolic and Nutritional Management of Duchenne Muscular Dystrophy	48 DMD patients	Metabolic syndrome, hepatic steatosis	Liver ultrasound, metabolic assessment	Total 40% of DMD patients had significant hepatic steatosis, increasing with disease progression
Kraus et al[19], 2016	Constipation in Duchenne Muscular Dystrophy: Prevalence, Diagnosis, and Treatment	120 DMD patients (5-30 years)	Functional constipation	Questionnaire, Bristol stool form scale, abdominal radiographs	Total 46.7% had functional constipation, often underdiagnosed and undertreated
Nart et al[20], 2023	Life-threatening bowel complications in adults with Duchenne muscular dystrophy: a case series	Adults with DMD	Colonic pseudo-obstruction, sigmoid volvulus	Case series, clinical review	Emphasized surgical risks and role of home parenteral nutrition
Hilbert et al[16], 2017	High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2	913 DM1 and 180 DM2 patients	Dysphagia, constipation, cholecystectomy	Patient-reported surveys, medical records	DM1 had higher rates of swallowing issues, while DM2 had more constipation
Tieleman et al[17], 2008	Gastrointestinal involvement is frequent in Myotonic Dystrophy type 2	29 DM2 patients, 29 DM1 patients, 87 controls	Dysphagia, abdominal pain, constipation	Questionnaires, colon transit study	GI dysfunction was as common in DM2 as in DM1, with slow colonic transit in 24%

BMD: Becker muscular dystrophy; DM: Myotonic dystrophy; DMD: Duchenne muscular dystrophy; GI: Gastrointestinal.

Table 2 Summary of case reports on gastrointestinal disorders in genetic myopathies

Ref.	Title of case report	Condition	Gastrointestinal manifestations	Management	Outcome
Dhaliwal et al[23], 2019	Gigantic Stomach: A Rare Manifestation of Duchenne Muscular Dystrophy	DMD	Severe gastric dilation, gastroparesis	Conservative management	Resolved without surgery
Barohn et al[24], 1988	Gastric Hypomotility in Duchenne’s Muscular Dystrophy	DMD	Acute gastric dilation, intestinal pseudo-obstruction	Autopsy study, gastric emptying tests	Found smooth muscle degeneration
Xie et al[34], 2020	Transaminitis in a Three-year-old Boy with Duchenne Muscular Dystrophy	DMD	Elevated liver enzymes, metabolic dysfunction	Enzyme tests, genetic sequencing	Diagnosed early, no liver damage found
Walsh et al[25], 2011	Progressive dysphagia in limb-girdle muscular dystrophy type 2B	Limb-girdle muscular dystrophy 2B	Progressive dysphagia for solids and liquids	Videofluoroscopy, genetic analysis	Confirmed Dysferlin mutations as the cause
Yoo et al[26], 2022	Clinical Course of Dysphagia in Patients with Nemaline Myopathy	Nemaline myopathy	Swallowing difficulties, aspiration risk	Tube feeding, dysphagia therapy	Improved swallowing over time
Glaser et al[27], 2015	Myotonic dystrophy as a cause of colonic pseudoobstruction: not just another constipated child	Myotonic dystrophy	Chronic intestinal pseudo-obstruction	Colectomy	Successful surgical outcome
Bayoumy et al[28], 2022	Sigmoid Volvulus in Myotonic Dystrophy Type I (Steinert Disease)	DM1 (Steinert disease)	Sigmoid volvulus	Endoscopic decompression	Resolved with conservative management
Dindyal et al[30], 2014	MELAS syndrome presenting as an acute surgical abdomen	MELAS syndrome	Toxic megacolon	Total colectomy	Diagnosis confirmed postoperatively
Sartoretti et al[29], 1996	Intestinal non-rotation and pseudoobstruction in myotonic dystrophy: case report and review of the literature	DM	Acute abdomen, ileus, aspiration pneumonia	Conservative therapy	Avoided surgery, symptoms controlled
Shaker et al[31], 1992	Manometric characteristics of cervical dysphagia in a patient with the Kearns-Sayre syndrome	Kearns-Sayre syndrome	Dysphagia, upper esophageal sphincter dysfunction	Manometry	Confirmed pharyngeal and esophageal dysmotility

DM: Myotonic dystrophy; DMD: Duchenne muscular dystrophy; MELAS: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.

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.

Table 4 Skeletal vs gastrointestinal smooth muscle: Similarities and dissimilarities

Feature	Skeletal muscle	Gastrointestinal smooth muscle
Excitable tissue	Yes	Yes
Contractile proteins	Actin and myosin	Actin and myosin
Sarcoplasmic reticulum	Yes	Yes
Contraction mechanism	Sliding filament	Sliding filament
Calcium dependence	Yes	Yes
Control	Voluntary	Involuntary
Innervation	Motor neurons	Autonomic nervous system
Hormonal regulation	Yes	Yes
Attachment to bone	Yes	No
Fiber nuclei	Multinucleated	Uninucleated
Fiber arrangement	Bundles of striated (striped) fibers	Sheets or layers of non-striated fibers
Contraction speed	Fast and powerful	Slow and sustained
Contraction pattern	Brief bursts	Tonic (sustained)
Dominant respiration	Anaerobic	Aerobic
Regeneration	Limited	Better capacity
Fatigue resistance	Susceptible	Highly resistant
Main control system	Central nervous system	Enteric nervous system

Table 5 Mechanism of gastrointestinal manifestations in genetic myopathies

Mechanism	Description
Smooth muscle dysfunction	Genetic mutations affecting smooth muscle cells can lead to contraction, coordination, and relaxation abnormalities, resulting in dysphagia, gastroesophageal reflux disease, gastroparesis, bloating, abdominal pain, constipation, diarrhea, and intestinal pseudo-obstruction
Skeletal muscle abnormalities	Dysfunction in skeletal muscles involved in voluntary control of the GI tract, such as pelvic floor muscles and the external anal sphincter, can cause fecal incontinence and difficulty with bowel movements. Weak abdominal muscles can hinder effective stool pushing during defecation. Weak masticatory muscles can lead to difficulty chewing and swallowing
Smooth muscle innervation and neuromuscular transmission	Genetic mutations can affect smooth muscle innervation and disrupt neuromuscular transmission in the enteric nervous system, leading to dysregulation of smooth muscle activity and symptoms such as diarrhea or constipation
Abnormal regulatory pathways	Disruption of neurotransmitters, hormones, and signaling pathways that regulate smooth muscle cells in the GI tract can result in abnormal smooth muscle contraction and relaxation patterns, contributing to GI symptoms
Systemic manifestations	Genetic myopathies can be associated with systemic abnormalities, such as metabolic disturbances and endocrine dysfunction, which indirectly impact the GI tract and contribute to GI symptoms, including impaired gut motility and nutrient absorption
Malabsorption	Chronic GI problems in genetic myopathies can lead to malabsorption of essential nutrients, resulting in deficiencies of vitamins, minerals, and electrolytes, which further impact overall health and exacerbate symptoms

GI: Gastrointestinal.

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.

Table 7 Comparison between magnetic resonance imaging and computed tomography in gastrointestinal myopathies

Feature	MRI	Computed tomography
Tissue contrast	Superior soft tissue contrast; excellent for detecting muscle atrophy, fibrosis, and inflammation	Moderate contrast; better for bony structures and acute bleeding
Radiation exposure	No ionizing radiation—safer for children and repeated follow-ups	Uses ionizing radiation, which may be concerning for pediatric patients and those needing serial imaging
Visualization of smooth muscle	More detailed assessment of intestinal wall abnormalities, fibrosis, and motility issues	Less sensitive in detecting smooth muscle pathology
Gastric and intestinal motility	MRI can provide cine imaging for real-time assessment of gastric emptying and intestinal movement	Lacks dynamic imaging capability for motility disorders
Bowel obstruction and pseudo-obstruction	Can differentiate between true obstruction vs pseudo-obstruction based on bowel wall motion	Effective for detecting acute bowel obstructions but lacks functional assessment
Detection of liver and pancreatic involvement	Better visualization of hepatic and pancreatic steatosis, common in metabolic myopathies	Good for detecting structural abnormalities, such as tumors or calcifications
Practical limitations	Longer scan time, requires patient cooperation, contraindicated in patients with metal implants	Quick scan time, widely available, useful for emergency settings

MRI: Magnetic resonance imaging.