What is DMD?: Duchenne muscular dystrophy is a severe type of muscular dystrophy, characterized by progressive muscle degeneration and weakness.
Initial Discovery:
First reported in the 1860s by Dr. Duchenne de Boulogne, noting muscle degeneration and cognitive difficulties.
Gene Identification:
In 1987, Dr. Eric Kaufman and Dr. Louis Lewis Huckle identified the dystrophin gene as the genetic basis for DMD, marking significant progress in genetic research.
Advancements in Care:
Late 1980s saw the introduction of respiratory support to prolong life expectancy, such as the use of ventilators and tracheostomy, which became more common worldwide in the early 2000s.
Steroid treatments (e.g., prednisone) began in the early 2000s to reduce inflammation in muscle tissue.
ACE inhibitors became part of standard care in 2007 to manage heart stress due to muscle weakening.
Early Mobility Issues:
Mobility challenges can present as early as infancy; parents might notice delayed walking.
Characteristic gait includes walking with shoulders back and knees together.
Pseudohypertrophy:
"Large calves" is a common symptom; however, this is due to muscle loss replaced by fat/connective tissue instead of true hypertrophy.
Prolonged Implications:
Mobility issues can lead to scoliosis, potentially requiring surgical correction.
Most patients are wheelchair-bound by age 12.
Cognitive Effects:
Many patients experience learning difficulties; early interventions can mitigate these issues.
Inheritance Pattern:
DMD follows an X-linked recessive inheritance pattern due to mutations in the dystrophin gene located at Xp21, the largest gene in the human genome with 89 exons.
Dystrophin Protein Characteristics:
Dystrophin weighs 427 kDa and consists of about 2.5 million base pairs.
Primarily expressed in cardiac muscles, brain, and retina.
Female Carriers:
Female carriers can exhibit mild symptoms due to reduced expression or functional dystrophin, occurring in 20% of cases.
Common Types of Mutations:
70-80% of mutations in DMD involve deletions or duplications that shift the open reading frame.
50-60% primarily consist of entire exon deletions.
30% of mutations are de novo—new mutations not inherited from parents, possibly influenced by maternal age.
Becker Muscular Dystrophy (BMD):
In-frame mutations lead to Becker muscular dystrophy, characterized by later onset and less severity compared to DMD.
Initial Testing:
Elevated creatine kinase levels in blood tests typically indicate muscle damage. Genetic testing follows for confirmation.
Muscle Biopsies:
Histological examination reveals damage and weakness in muscle cells, aiding in diagnosis.
Electrocardiograms (EKGs):
Monitor cardiovascular health, crucial due to eventual heart muscle weakening.
Genetic Counseling:
Recommended for families with a history of DMD who plan to have children, assessing genetic risks due to the fatal nature of the disease.
Monitoring and Early Intervention:
Cardiac monitoring and intervention typically start at age 10; beginning attention to cardiovascular health is critical at diagnosis.
Medications:
ACE inhibitors and angiotensin receptor blockers help reduce blood pressure and heart stress.
Steroid treatments like prednisone also slow muscle degeneration and can mitigate the need for surgeries.
Respiratory Support:
As the disease progresses, patients may require a ventilator or tracheostomy due to diaphragm muscle weakness.
Exon Skipping Therapy:
A promising approach being researched to restore dystrophin function in muscle.
Physical Therapy:
Vital for maintaining ambulation and prolonging patients' walking abilities as long as possible.
Life Expectancy:
Average life expectancy for DMD patients is approximately 23.7 years; early diagnosis and intervention can improve this outlook significantly.
Care for Female Carriers:
Monitoring them is important, though their symptoms are typically less severe due to having a single affected allele.
Becker Muscular Dystrophy:
Less severe and later-onset, offers more effective longitudinal research due to longer survival, providing insights into disease progression and treatment options.
Dickens Muscular dystrophy
What is DMD?: Duchenne muscular dystrophy is a severe type of muscular dystrophy, characterized by progressive muscle degeneration and weakness.
Initial Discovery:
First reported in the 1860s by Dr. Duchenne de Boulogne, noting muscle degeneration and cognitive difficulties.
Gene Identification:
In 1987, Dr. Eric Kaufman and Dr. Louis Lewis Huckle identified the dystrophin gene as the genetic basis for DMD, marking significant progress in genetic research.
Advancements in Care:
Late 1980s saw the introduction of respiratory support to prolong life expectancy, such as the use of ventilators and tracheostomy, which became more common worldwide in the early 2000s.
Steroid treatments (e.g., prednisone) began in the early 2000s to reduce inflammation in muscle tissue.
ACE inhibitors became part of standard care in 2007 to manage heart stress due to muscle weakening.
Early Mobility Issues:
Mobility challenges can present as early as infancy; parents might notice delayed walking.
Characteristic gait includes walking with shoulders back and knees together.
Pseudohypertrophy:
"Large calves" is a common symptom; however, this is due to muscle loss replaced by fat/connective tissue instead of true hypertrophy.
Prolonged Implications:
Mobility issues can lead to scoliosis, potentially requiring surgical correction.
Most patients are wheelchair-bound by age 12.
Cognitive Effects:
Many patients experience learning difficulties; early interventions can mitigate these issues.
Inheritance Pattern:
DMD follows an X-linked recessive inheritance pattern due to mutations in the dystrophin gene located at Xp21, the largest gene in the human genome with 89 exons.
Dystrophin Protein Characteristics:
Dystrophin weighs 427 kDa and consists of about 2.5 million base pairs.
Primarily expressed in cardiac muscles, brain, and retina.
Female Carriers:
Female carriers can exhibit mild symptoms due to reduced expression or functional dystrophin, occurring in 20% of cases.
Common Types of Mutations:
70-80% of mutations in DMD involve deletions or duplications that shift the open reading frame.
50-60% primarily consist of entire exon deletions.
30% of mutations are de novo—new mutations not inherited from parents, possibly influenced by maternal age.
Becker Muscular Dystrophy (BMD):
In-frame mutations lead to Becker muscular dystrophy, characterized by later onset and less severity compared to DMD.
Initial Testing:
Elevated creatine kinase levels in blood tests typically indicate muscle damage. Genetic testing follows for confirmation.
Muscle Biopsies:
Histological examination reveals damage and weakness in muscle cells, aiding in diagnosis.
Electrocardiograms (EKGs):
Monitor cardiovascular health, crucial due to eventual heart muscle weakening.
Genetic Counseling:
Recommended for families with a history of DMD who plan to have children, assessing genetic risks due to the fatal nature of the disease.
Monitoring and Early Intervention:
Cardiac monitoring and intervention typically start at age 10; beginning attention to cardiovascular health is critical at diagnosis.
Medications:
ACE inhibitors and angiotensin receptor blockers help reduce blood pressure and heart stress.
Steroid treatments like prednisone also slow muscle degeneration and can mitigate the need for surgeries.
Respiratory Support:
As the disease progresses, patients may require a ventilator or tracheostomy due to diaphragm muscle weakness.
Exon Skipping Therapy:
A promising approach being researched to restore dystrophin function in muscle.
Physical Therapy:
Vital for maintaining ambulation and prolonging patients' walking abilities as long as possible.
Life Expectancy:
Average life expectancy for DMD patients is approximately 23.7 years; early diagnosis and intervention can improve this outlook significantly.
Care for Female Carriers:
Monitoring them is important, though their symptoms are typically less severe due to having a single affected allele.
Becker Muscular Dystrophy:
Less severe and later-onset, offers more effective longitudinal research due to longer survival, providing insights into disease progression and treatment options.