A Comprehensive Review of Duchenne Muscular Dystrophy: Genetics, Clinical Presentation, Diagnosis, and Treatment

Duchenne muscular dystrophy (DMD)

Duchenne Muscular Dystrophy (DMD) is an X linked recessive disease caused by a mutation in the DMD gene encoding for the dystrophin protein. DMD is characterized pathologically as a complete absence of the cytoskeletal protein DMD is characterized clinically by progressive muscle weakness with the distribution of predominant muscle fragility in the proximal extremities, neck, and chest. DMD is the most common of the muscular dystrophies, and one of the most common fatal neuromuscular disorders, affecting 1 in 3,500 newborn boys. The clinical presentation begins early in childhood with progressive muscle wasting and weakness, eventually leading to death. The protein defect is present at birth but is not typically clinically observed and diagnosed until the second or third year of life. ^[1,2,3,4.]This disease eventually leads to the inability to walk with an associated wheelchair requirement around age 12, severe scoliosis secondary to muscle weakness, and eventual death due to cardiac and/or respiratory failure by the mid-twenties, especially in those patients not choosing ventilator support.The human DMD gene resides at locus Xp21.2 and produces a rod-shaped cytoplasmic structural protein primarily in skeletal muscle with isoforms in cardiac muscle, smooth muscle, brain nerve cells, and the retina. The DMD gene is 2.3 Mb in humans with 79 exons, producing a 14 kb RNA and 427 kDa protein. One-third of DMD cases are due to a de novo mutation, and two-thirds of cases are of familial origin, usually from a female carrier. Becker Muscular Dystrophy (BMD) is a less severe form of muscular dystrophy in which similar symptoms appear but with a slower and less severe progression. Statistical analysis found the global prevalence of DMD to be three times higher than the rate of BMD. Global DMD prevalence is around 7.1 per 100,000 males and 2.8 per 100,000 of the general population. DMD incidence was found to be 19.8 per 100,000 live male births.It was found that from 2006 to 2015 in the U.S., 3,256 deaths were due to DMD in the male population under 40 years of age, with 71% of these mortalities being confined within the age range of 15 to 29 years of age . Though it is unusual for X-linked disorders to demonstrate different frequencies across different racial groups, muscular dystrophies (MD) have drastically different^[5,6,7]affected racial populations. It appears MD are statistically higher in the Caucasian male population than males in other racial groups. Caucasian American males experience an average annual death rate of 0.43 per 100,000 from MD, compared to that of African American males, which have a rate of 0.28 per 100,000^[9,10,11]Native Americans and Alaska Natives are found to have 0.20 deaths per 100,000 and Asian and Pacific Islanders with 0.21 deaths per 100,000. Hispanic white and non-Hispanic whites also had different rates of MD incidences. Hispanic whites have a death rate from MD of 0.31 per 100,000, as compared to non-Hispanic whites with a rate of death of 0.46 per 100,000 . Children born with DMD are of normal height and weight at birth but often fall below the expected growth curves during early childhood. Boys born to families without a past medical history of DMD are normally diagnosed during the fourth year of life. Dystrophic myopathy presents with rapid, progressive muscle degeneration and a loss of functional skeletal muscle over time. Motor delays or abnormal gait are the most common presenting symptoms.Other presentations may include communication disorders such as language delays, or overall global developmental delays.

Figure No.1: Duchenne muscular dystrophy (DMD)

Genetic basis: X-linked recessive inheritance, mutation in the DMD gene

DMD is a genetic disease due to the mutation of the dystrophin gene, located on chromosome Xp21. It is inherited as an X- linked recessive trait; however, approximately 30% of cases are due to new mutations.Mutations in the dystrophin gene result in diseases known as^[13,14]dystrophinopathies, which encompass Duchenne muscular dystrophy, Becker muscular dystrophy, and an intermediate form. Mutations result in a limited production of the dystrophin protein, which results in loss of the myofiber membrane integrity with repeated cycles of necrosis and regeneration. Fibrous connective tissue and fat progressively replace muscle leading to clinical features.Carrier females show no evidence of muscular weakness; however, symptomatic female carriers have been described. About 2.5% to 20% of female carriers may be affected. Genetic basis: X-linked recessive inheritance, mutation in the DMD gene. This can be explained by the Lyon hypothesis in which the normal X chromosome becomes inactivated,

Figure No.2: X-linked recessive inheritance in DMD

Genetic basis: X-linked recessive inheritance, mutation in the DMD gene.

This can be explained by the Lyon hypothesis in which the normal X chromosome becomes inactivated, and the X chromosome with the mutation is expressed.Female carriers can become symptomatic^[15,16]if they are associated with Turners syndrome (45X) or mosaic Turner karyotype, balanced X autosome translocations with breakpoints within the dystrophin gene and preferential inactivation of the normal X, and females with a normal karyotype but with nonrandom X chromosome inactivation with diminished expression of the normal dystrophin allele.

ETIOLOGY & PATHOGENESIS

Muscular dystrophy is a group of inherited diseases marked by skeletal muscle degeneration and weakness. This condition progresses due to the loss of healthy muscle fibers over time, which are replaced by fibrosis and fat. This leads to reduced muscle force generation for everyday activities. Different forms of muscular dystrophy can affect various muscle groups differently. Respiratory failure can arise from weakened breathing muscles, potentially shortening lifespan unless mechanical support is employed. Some types of muscular dystrophy also impact the heart, leading to cardiac issues like heart failure and irregular rhythms. The dystrophin^[17,18,19]gene is the largest known human gene, comprising 79 exons spanning over 2,200 kb, which accounts for about 0.1% of the entire genome. The most common mutation causing Duchenne muscular dystrophy (DMD) involves a deletion affecting one or multiple exons, accounting for 60-70% of cases. Point mutations contribute to around 26% of DMD cases, while exonic duplications account for 10-15%. Other mutations, such as subexonic insertions, deletions, splice mutations, and missense mutations, make up the remaining cases. Mutations leading to DMD disrupt the protein's reading frame, causing early stop codons and resulting in unstable or absent protein production in cells. The dystrophin-associated proteins are categorized based on cellular location: extracellular (α dystroglycan), transmembrane (β-dystroglycan, sarcoglycans, sarcospan), and cytoplasmic (dystrophin^[20,21]dystrobrevin, syntrophins, neuronal nitric oxide synthase). α-dystroglycan, a receptor for extracellular ligands, resides on the outer sarcolemma due to its glycosylation and membrane association. It interacts closely with β-dystroglycan, a transmembrane protein also binding to dystrophin. Mutations affecting glycosylation enzymes (POMT1, POMT2, POMGnT1, FKTN, FKRP) lead to limb-girdle muscular dystrophies (LGMD2I, K, M, N, O), while other gene mutations disrupt α-dystroglycan glycosylation and cause congenital muscular dystrophies. Dystrophin-glycoprotein complex (DGC) consists of dystrophin linking intracellular cytoskeleton to transmembrane components like dystroglycan, sarcoglycans, and sarcospan. Sarcoglycans form a complex with sarcospan, aiding in structural support, signal transduction, and mechanoprotection^[22]At the sarcolemma, the sarcoglycan complex tightly associates with β-dystroglycan. Dystrophin interacts with β dystroglycan intracellularly, connecting the cytoskeleton to DGC, and further to the extracellular matrix. Cytoplasmic components like α-dystrobrevin, syntrophins, and neuronal nitric oxide synthase (nNOS) are involved in signal transduction and exercise-induced blood flow regulation. Duchenne muscular dystrophy (DMD) is a lethal condition causing progressive muscle weakness due to mutations in the DMD gene. Dystrophin, encoded by this gene, connects DGC with the intracellular cytoskeleton. Therapies have been developed to manage DMD^[23,24]although no absolute cure exists. DMD mutations can disrupt the reading frame, leading to severe DMD, or maintain it, causing less severe Becker muscular dystrophy (BMD). Recent findings suggest that DMD could also be a stem cell disease, with abnormalities in muscle stem cells contributing to the pathophysiology.

Figure No.3: Dystrophin's Role in Muscle Integrity and Duchenne Muscular Dystrophy

Dystrophin's Role in Muscle Integrity and Duchenne Muscular Dystrophy 

Dystrophin is a critical protein involved in maintaining the integrity of muscle cells during repeated cycles of contraction and relaxation associated with muscle activity. It acts as an anchor between the actin cytoskeleton and the Dystrophin-associated glycoprotein complex (DGC) at the muscle cell membrane, known as the sarcolemma. This connection helps stabilize the muscle cell and prevents damage caused by mechanical stress. The extracellular domain of the DGC binds to the extracellular matrix protein laminin, further contributing to muscle stability. Duchenne muscular dystrophy (DMD) is a severe X-linked disorder affecting approximately 1 in 3600 males during early childhood. It results from mutations in the dystrophin gene, leading to a loss of functional dystrophin protein. This absence of dystrophin makes the sarcolemma unstable, causing muscle fibers to be susceptible to damage following muscle contractions. Muscle weakness in DMD arises from a cycle of damage and regeneration, which eventually exhausts the muscle's regenerative capacity.

Inflammatory Response in DMD

Muscle damage in healthy muscles triggers an inflammatory response, involving immune cell recruitment, chemokine and cytokine secretion, and oxidative stress. Immune cells aid tissue regeneration by promoting the proliferation and maturation of satellite cells, which are precursor cells for muscle fibers^[25,26]. However, in DMD, the prolonged activation of the innate immune response results in chronic inflammation and additional tissue damage. The continuous damage-repair cycle causes the release of damage-associated molecular patterns (DAMPs) from muscle cells into the extracellular space. These DAMPs, including proteins like HMGB1, ATP, and RNA, sustain immune cell activation and lead to chronic inflammation.

Multi-System Abnormalities and Clinical Manifestations

DMD's impact is not limited to muscles; it also affects multiple systems. Patients experience progressive muscle weakness, with initial symptoms appearing in early childhood. As the disease progresses, muscle weakness spreads, affecting different muscle groups and causing difficulties in motor skills. Cognitive dysfunction, orthopedic complications, and cardiac issues are common. With advancements in management and therapies, individuals with DMD are living longer, and heart problems have become an important cause of mortality.

Duchenne muscular dystrophy causes progressive muscle weakness due to muscle fibre disarray, death, and replacement with connective tissue or fat. The voluntary muscles are affected first, especially those of the hips, pelvic area, thighs, calves. It eventually progresses to the shoulders and neck, followed by arms, respiratory muscles, and other areas. Fatigue is common.

Signs usually appear before age five, and may even be observed when a boy takes his first steps.There is general difficulty with motor skills, which can result in an awkward manner of walking, stepping, or running. They tend to walk on their toes, in part due to shortening of the Achilles tendon, and because it compensates for knee extensor weakness.Falls can be frequent.It becomes increasingly difficult for the boy to walk. The ability to walk usually disintegrates completely before age 13.Most men affected with Duchenne muscular dystrophy become essentially "paralyzed from the neck down" by the age of 21. Cardiomyopathy, particularly dilated cardiomyopathy, is common, seen in half of 18-year-olds.The development of congestive heart failure or arrhythmia (irregular heartbeat) is only occasional.In late stages of the disease, respiratory impairment and swallowing impairment can occur, which can result in pneumonia.

Figure No.4:  Signs and symptoms

Figure No.5: Ratio of Signs and Symptoms of Duchenne Muscular Dystrophy (DMD)

Figure No.6:  Signs and Symptoms of Duchenne Muscular Dystrophy (DMD) order of Frequency

Diagnosis and Genetic Testing

Diagnostic Approaches:

Serum creatine kinase (CK) levels are elevated before clinical symptoms and peak by age two, often 10 to 20 times the upper limit of normal.

Muscle biopsy reveals connective tissue proliferation, muscle fibre necrosis, and replacement with adipose tissue.

Genetic testing detects mutations in the dystrophin gene. Immunoblotting can predict disease severity. Polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) are used to identify mutations

Cardiac and Respiratory Involvement:

DMD leads to dilated cardiomyopathy in most patients by their teens or twenties

Respiratory complications are common, and patients may die due to respiratory and cardiac issues by their early twenties.

Management:

There's no cure for DMD, but management focuses on symptom relief, complications, and improving quality of life

Treatments include glucocorticoids, rehabilitation, cardiac and respiratory management, and psychosocial care.

Diagnostic Testing:

Creatine kinase (CK) testing is commonly used for diagnosis. It shows high specificity (90%) and sensitivity (80%) in detecting DMD.

Elevated CK levels are indicative of muscle damage and are present even before symptom onset.

Neonatal Screening and CK:

Neonatal screening for DMD using CK testing has been discussed. It offers the advantage of early diagnosis and intervention.

CK testing in neonatal screening has shown high specificity and sensitivity in identifying true DMD cases.

Figure No.7: Newborn Screening Spotlight

Limitations:

? While CK testing is useful, it's important to note that the test itself does not determine the specific type of muscle disorder. The provided data offers a comprehensive overview of DMD, including its clinical presentation, diagnostic methods, genetic aspects, and management strategies. If you need more detailed information or specific insights from the data, feel free to ask.

Figure No.8: Diagnostic decision to confirm the genetic diagnosis of dystrophinopathies.

Genetic Testing and Biomarkers in Duchenne Muscular Dystrophy (DMD)

Genetic testing is pivotal in diagnosing Duchenne Muscular Dystrophy (DMD), a severe muscle-wasting disorder caused by mutations in the dystrophin gene. This gene, the largest known human gene, comprises 79 exons spanning 2.2 Mb. The mutation rate is relatively high, with about one in three DMD cases resulting from de novo mutations. DMD is characterized by impaired muscle function, frequent falls, delayed speech, and elevated muscle enzymes in affected boys. Genetic Diagnosis: Diagnostic strategies involve identifying mutations through multiplex ligation dependent probe amplification (MLPA), array comparative genome hybridization (array CGH), or Sanger sequencing. MLPA and array CGH detect exon deletions and duplications, with MLPA also detecting small mutations. Sanger sequencing is used for confirming exon-level mutations. The shift towards next generation sequencing (NGS) techniques is promising but currently not as cost-effective as traditional methods. Biomarkers for DMD: Biomarkers are vital for monitoring DMD progression and assessing treatment efficacy. Creatine kinase (CK) is a well-known biomarker for muscle damage, though not specific enough for diagnosis. Other proteins, including carbonic anhydrase 3 (CA3), malate dehydrogenase 2 (MDH2), myosin light chain 3 (MYL3), troponins, and inflammatory markers, show potential as biomarkers for different aspects of DMD progression. These biomarkers often exhibit declining abundance trajectories as the disease advances, making them more informative during early stages. Complexity of Biomarkers: DMD's multifaceted nature necessitates the use of biomarker panels or signatures to comprehensively describe disease progression. Different biomarkers are associated with muscle function, inflammation, fibrosis, and cardiac status. As the disease evolves, a combination of biomarkers offers a more accurate representation of its progression.

A muscle biopsy will demonstrate endomysial connective tissue proliferation, scattered degeneration, and regeneration of myofibers, muscle fibre necrosis with a mononuclear cell infiltrate, and replacement of muscle with adipose tissue and fat

 Evaluation

Muscle Biopsy

A muscle biopsy will demonstrate endomysial connective tissue proliferation, scattered degeneration, and regeneration of myofibers, muscle fibre necrosis with a mononuclear cell infiltrate, and replacement of muscle with adipose tissue and fat

Figure No.9: Muscle Biopsy

Electromyography

Characteristic myopathic features can be seen; however, this is nonspecific. Motor and sensory nerve conduction velocities are normal, and denervation is not present.

Figure No.10: Electromyography

Gene Analysis

Patients with DMD demonstrate the complete or near-complete absence of dystrophin gene. Dystrophin immunoblotting can be used to predict the severity of the disease. In DMD, patients are found to have less than 5% of the normal quantity of dystrophin.

Polymerase chain reactions (PCR) can also be used and detect up to 98% of mutations. Multiplex ligation-dependent probe amplification (MPLA) is also used to identify duplications and deletions. Duplications can lead to in-frame or out of frame transcription products. Fluorescence in situ hybridization (FISH) is used less frequently but is useful to identify small point mutations.

Figure No.11: Gene Analysis

Electrocardiogram (ECG)

Characteristic ECG changes are tall R waves in V1-V6 with an increased R/S ratio and deep Q waves in leads I,aVL, and V5-6. Conduction abnormalities with arrhythmias may be identified with telemetry. As mentioned previously, supraventricular arrhythmias are more common. Intra-atrial conduction abnormalities are more common than AV or infra-nodal defects in DMD.

TREATMENT AND MANAGEMENT

Glucocorticoid Therapy

Glucocorticoid therapy decreases the rate of apoptosis of myotubes and can decelerate myofiber necrosis. Prednisone is used in patients four years and older in whom muscle function is declining or plateauing.

Deflazacort, an oxazoline derivative of prednisone, is sometimes preferred over prednisone as it has a better side effect profile and has an estimated dosage equivalency of 1:1.3 compared with prednisone. The recommended dosage is 0.9 mg/kg/day.

Cardiomyopathy

Treatment with angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers is recommended. Early studies suggest that early treatment with ACE inhibitors may slow progression of the disease and prevent the onset of heart failure.

Overt heart failure is treated with digoxins and diuretics as in other patients with cardiomyopathy.

Pulmonary Interventions

Pulmonary function must be tested prior to the exclusive use of a wheelchair. This should be repeated twice a year once the patient reaches 12 years of age, must use a wheelchair or vital capacity is found to be less than 80% of predicted.

Orthopaedic Interventions

Physiotherapy to prevent contractures is the mainstay of the orthopedic interventions. Based upon patient requirements, passive stretching exercises, plastic ankle-foot orthosis during sleep, long leg braces to assist in ambulation may be used. Surgery to release contractures may be required for advanced disease. Surgery to correct scoliosis may improve pulmonary function.

Nutrition

Patients are at risk for malnutrition, including obesity. Calcium and vitamin D should be supplemented to prevent osteoporosis secondary to chronic steroid use. DEXA scanning should be obtained at age three and then repeated yearly.

Exercise

Guidelines recommend all patients participate in a gentle exercise to avoid disuse atrophy. A combination of swimming pool and recreation-based exercises is recommended. Activity should be reduced if myoglobinuria is noted or significant muscle pain develops.

Figure No.12: Exercise to avoid disuse atrophy

Novel Therapies

Gene therapies include medications that bind RNA and skip over the defective codon. This produces a shorter but potentially functional protein. Eteplirsen us an exon 51 skipping antisense oligonucleotides medications used for this purpose. Eteplirsen has been approved by the FDA for this purpose.

Corticosteroids: prednisone and deflazacort

Glucocorticoids, more precisely prednisone and deflazacort, are the main drug treatment for DMD. They have been used for over two decades and the benefits are well known now. They are the only medication that has been shown to increase muscular strength. Early studies have proved that their use prolonged ambulation and improved their functionality in everyday activities. Longterm studies have shown that they also reduce the need for scoliosis surgery, enhance lung function, and help maintain cardiac function.

The new drugs approved by the FDA for the treatment of Duchenne muscular dystrophy (DMD) 2024 are:

(givinostat) — Approved March 21, 2024

Type: First-ever nonsteroidal oral treatment for DMD.

Indication: For patients aged 6 years and older, regardless of their specific DMD mutation.

Mechanism: A histone deacetylase (HDAC) inhibitor that helps reduce muscle inflammation and slows disease progression.

Figure No.13: Nonsteroidal oral treatment for DMD

Clinical evidence: In a Phase 3 trial (EPIDYS), after 18 months, patients on Duvyzat had significantly less decline in their time to climb four stairs (mean increase of 1.25 seconds vs. 3.03 seconds for placebo), plus better outcomes in motor assessments.

Side effects: Most were mild to moderate—diarrhea, abdominal discomfort, nausea, thrombocytopenia, elevated triglycerides, fever, etc.

Elevidys (delandistrogene moxeparvovec-rokl) — Expanded approval June 20, 2024

Type: A gene therapy previously approved in 2023 under accelerated approval for ambulatory children aged 4–5

2024 Update: FDA expanded its indication to include:

Traditional approval for ambulatory patients aged 4 years and older.

Accelerated approval for non-ambulatory patients aged 4 years and older—continuation of this approval hinges on confirmatory trial results.

Mechanism: Delivers a shortened micro-dystrophin gene via an AAV vector, aiming to produce functional dystrophin in muscle cells.

Figure No.14: Elevidys (delandistrogene moxeparvovec-rokl)

Cardiac Management:

The text suggests that in the ambulatory stages of DMD, cardiac function should be assessed at diagnosis using methods like ECG and echocardiogram. Angiotensin converting enzyme inhibitors or angiotensin receptor blockers are recommended by age 10, and cardiac function should be assessed annually. After the loss of ambulation, regular assessment continues, and heart failure medical therapy is initiated if needed.

Genetic Therapy:

Genetic therapy, involving the insertion of the dystrophin gene, is explored. Challenges like gene size have led to the development of smaller genes. A virus-associated with adenovirus is used as a vector, but immune responses hinder success.

Pulmonary Management:

Most individuals with DMD eventually face respiratory complications. Muscle weakness affects inspiratory and expiratory muscles, leading to hypoventilation and elevated CO2 levels. This places patients at risk of pneumonia.

Exon Skipping:

Exon skipping aims to restore reading frames. Synthetic RNA molecules, antisense oligonucleotides (AO), are developed. Studies target specific exons like exon 51 using 2'-O-methyl phosphorotioates (2OMP) and phosphorodiamidate morpholino oligomers (PMOs

Phosphodiesterase Inhibitor;

Sildenafil, a phosphodiesterase type 5 inhibitor, improves nitric oxide signalling, benefiting vasculature, muscle mass, and fibre type. It's muscle-specific and improves force production.

Exercise:

Limited motor abilities are common in DMD. Physiotherapy focuses on stretching upper and lower extremity muscles, pool therapy, and gentle physical activity. Disease-specific physical therapy maintains strength, flexibility, and function

Vitamin D Supplement:

DMD patients are at risk of fractures due to decreased bone density and corticosteroid treatment. Vitamin D supplementation is advised for those with deficiency. Orthopaedic appliances and respiratory support are important.

Figure No.15: Vitamin D Supplement

Impact on Patients and Families;

The impact of Duchenne muscular dystrophy (DMD) on patients and their families is profound, extending to psychological and emotional aspects. Here are some key points:

1. Emotional Distress: DMD's progressive nature and its impact on mobility can lead to emotional distress for both patients and their families. Feelings of sadness, frustration, and anxiety are common.

2. Quality of Life: DMD can significantly affect a patient's quality of life due to the loss of physical abilities. This can lead to feelings of social isolation and a sense of missing out on typical childhood experiences.

3. Coping Mechanisms: Patients and families develop various coping mechanisms to deal with the challenges of DMD. These can include support groups, counseling, and learning to adapt to new routines and requirements.

4. Caregiver Stress: Family members, often parents, who serve as primary caregivers for DMD patients may experience high levels of stress and burnout due to the demanding nature of caregiving.

5. Hope and Resilience :Despite the challenges, many individuals and families affected by DMD demonstrate remarkable resilience and find hope in research advancements and support networks.

6. Impact on Siblings: DMD also affects siblings, who may feel neglected or burdened by the condition's demands. Open communication within the family is essential to address.

Ayurvedic Management of Duchenne Muscular Dystrophy

Nidan Panchaka of DMD According to Ayurveda

Nidan Panchaka entails five essential components. Firstly, “Hetu” identifies the cause or root factor contributing to the disease. Secondly, “Purvarupa” highlights the early symptoms or indicators that precede the full manifestation of the illness. Thirdly, “Rupa” describes the characteristic features and presentation of the disease, aiding in its recognition and diagnosis. Fourthly, “Upshaya” refers to relieving factors, guiding therapeutic strategies. Lastly, “Samprapti” elucidates the progression and course of the disease, including its natural history and potential complications.

Nidan/Hetu (causative factors):

The pathological condition manifests as a partial vitiation observed either in Shukra, the reproductive tissue, or Shonita, the blood component, within the physiological framework. This aberration is further characterised by a specific defect in the Beejabhag or Beejabhagavaya, indicative of a chromosomal abnormality specifically localised on the Xp21 chromosome. Moreover, the intricacies of this defect extend into the Matruj Bhava, underscoring the involvement of maternal factors, as the genesis of Mamsa, the muscular tissue, is intricately linked with these maternal influences.

Figure No.16: Nidan/Hetu (causative factors)

Purvarupa:

The identification of a developing movement deficit in a child’s developmental trajectory serves as a key indicator of the vitiation of Vata, a fundamental concept in Ayurveda highlighting the imbalance in the bodily Vata Dosha and Kapha elements. Furthermore, the compromise in metabolic functions is intricately linked to Pitta Dushti, denoting an imbalance in the Agni and Jala^[27]elements within the physiological framework. In a parallel context, the erosion of the quality characterised by “Sthiratva,” emphasising stability and steadfastness, is a consequential outcome attributed to the influence of Kapha Dushti.

Roop (characteristic features):

“Rupa” includes the characteristic features and presentation of the disease (signs and symptoms) and diagnosis.

Upashaya (relieving factors):

Temporary relief occurs due to Panchakarma procedures including Shaman Chikitsa, also helps to increase quality of life without using steroidal formulation.

Samprapti of the disease:

“Samprapti” elucidates the progression and course of the disease, including its natural history and potential complications.

Samprapti Ghatak (Aetiopathogenesis) Ayurvedic management of DMD:

DMD, as mentioned in,viewed through the lens of Ayurveda, involves a disruption in the equilibrium of Tridosha, impacting vital bodily tissues such as Rasa, Rakta, and Mamsadhatu.

The disturbance extends to Agni, encompassing Jatharagni, Rakta, and Mamsa Dhatvagni, signifying an imbalance in metabolic processes. Identified within the Adhishthan of Mamsa or muscle tissue, the condition is recognised for its complexity.

Figure No.17: Samprapti Ghatak (Aetiopathogenesis) Ayurvedic management of DMD