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Congenital Muscular Dystrophy

Editor: Prasanna Tadi Updated: 7/3/2023 11:39:16 PM


Congenital muscular dystrophy is one of the variants of muscle weakness disorders presenting early in life during infancy and soon after birth. The difference between congenital myopathies and muscular dystrophies is that dystrophies are gradually progressive and are associated with increased muscle breakdown with age.[1] Congenital myopathies signify disorders associated with muscle weakness in the neonatal age group, which could be secondary to genetic, metabolic, or other disorders and usually have a non-progressive course. Classification of these groups of disorders is based on findings on muscle biopsy and genetic evaluation. The muscle biopsy findings common for these disorders are muscle fiber atrophy, fibrofatty infiltration of tissue.


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Most of these disorders are inherited and linked to specific genes. These affect the synthesis of various proteins at the plasma membrane extracellular matrix interface. The most common mode of inheritance is autosomal recessive. Duchenne is X linked and is, therefore, is seen only in boys. The majority of the females are carriers, but some can have mild to moderate muscle weakness. Both Duchenne and Becker dystrophy result from a mutation in the dystrophin gene, the locus of which is Xp21.2. Duchenne dystrophy results when the protein is abnormally truncated, whereas Becker dystrophy is from partially functional dystrophin.[2]

Other congenital dystrophies include walker Warburg, muscle eye brain, and Fukuyama disease are together called a- dystroglycanopathies (because of mutation seen in a common protein a-dystroglycan). Myotonic dystrophy is usually transmitted as autosomal dominant and results from trinucleotide (CTG) repeat expansion on the of the DMPK gene at locus 19q13.3.[3] Ulrich and Bethlehem myopathy both results from the alteration of the collagen VI molecules in three known genes, COL6A1, COL6A2, and COL6A3 and may be autosomal recessive or dominant.


Out of all the congenital muscular dystrophies, Duchenne muscular dystrophy is the most common, and its incidence is around 1 in 3600 boys.[4] The incidence of congenital muscular dystrophies in children in population-based studies was estimated to be around 0.82/100,000 children.[5] The prevalence of specific types can also be common depending on the geographical area like Fukuyama muscular dystrophy is the most common type in Japan.[6]


The deletion or malformation of specific proteins secondary to inherited or de-novo mutations results in abnormal protein structure or function and thereby causing muscle weakness. The common forms of congenital muscular dystrophies result from alterations in plasma membrane surface proteins or those forming a part of the membrane-extracellular matrix interface.[7] The discovery of merosin, which is an extracellular matrix protein, leads to the classification of the disease into merosin positive and merosin negative forms. The merosin negative form was associated with marked motor disability, high creatine kinase levels, and relatively normal IQ scores.[8] However, the merosin negative patients were associated with abnormal MRI white matter findings with sparing of basal ganglia.[9]

The major categories of congenital muscular dystrophies based on the proteins affected are

  1. Collagen type VI related – Ulrich (severe variant) and Bethlehem (milder) myopathy[10]
  2. Merosin related – this includes patients with a mutation in laminin alpha 2 protein which is merosin deficient[11]
  3. Alpha dystroglycan related – including walker Warburg, muscle eye brain and Fukuyama myopathy (Fukutin gene at 9q31-33)[12] and limb-girdle muscle dystrophy

The correlation between genotype and phenotype depends on the affected protein being completely deficient or partially deficient, which is determined by the type of mutation in the gene.

History and Physical

Antenatally pregnancies of patients affected with muscular dystrophies may show polyhydramnios due to decreased swallowing of amniotic fluid and reduced fetal movements in utero. At birth, these patients may present with a poor feeble cry and minimal spontaneous movements of the extremities along with hypotonia on examination, and the most severe variants can have contractures at birth.[13]

On asking the parents, a history of poor feeding can be elicited, which is secondary to poor suck. Significant motor delay can be one of the other presenting symptoms during childhood. The severity of muscle weakness in these patients depends on the type of disease and the abnormal protein being completely or partially affected. All infants suspected to have hypotonia should have a thorough physical examination done to rule out anomalies affecting other organs and to look for the possible syndromic association.[14]

The timing of onset (infancy vs. childhood) and type of muscles (proximal vs. distal) involved are clues towards limiting the differential diagnosis to a smaller subset of disorders.


The screening workup of an infant with hypotonia should include:

  • A thorough history and clinical examination documenting power at each of the joints and reflexes should be done by a neurologist.
  • A creatine kinase level (CK), aldolase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), nerve conduction studies and EMG should be considered. However, creatine kinase levels may vary from being completely normal to significantly elevated based on phenotype. An elevated CK, aldolase level, usually signifies a dystrophic process.
  • Muscle biopsy, which was earlier done routinely as a part of the evaluation for these disorders is no longer used in all cases with the advent of genomic sequencing. Immunohistochemistry and electron microscopy may help to identify specific diseases based on staining patterns.
  • Echocardiography and EKG should be performed to look for cardiomyopathy and abnormal conduction, which can commonly occur in these disorders if the abnormal protein is also expressed in cardiac myocytes.
  • Imaging of the brain with MRI should be done when possible, as many of these disorders are associated with specific abnormalities in different areas of the brain on imaging sequences.
  • Specific diseases like Fukuyama dystrophy and muscle eye brain disease are associated with eye abnormalities like myopia, strabismus, cataract, and glaucoma in a significant subset of patients. 
  • Confirmatory testing for most of these disorders requires testing for a specific protein or genetic change or mutation which is based on the underlying disorder and should preferably be conducted in a laboratory specialized to perform genetic testing.

Treatment / Management

  • Management of most of these disorders is supportive since the replacement of specific proteins and genes has been tried mostly in animal models. The use of these medications and gene therapy in humans has been part of clinical trials.[15]
  • Most centers managing such patients now have interprofessional teams, which include multiple subspecialists to help caregivers take care of these patients with multiple complex needs at home.
  • Assisted mechanical ventilation is done at home with the help of parents and home nursing if respiratory muscles are affected.
  • Intensive physical and occupational therapy is an essential part of the care of these patients while they are admitted to the hospital and should be continued at home.
  • These patients require surgical intervention for other comorbidities like scoliosis due to prolonged immobility, placement of feeding gastrostomy, or gastrojejunostomy tube to keep up with nutritional requirements.[16]
  • Nutritional support plays a significant role in long term management of these patients as they are usually underweight, and macro/micronutrient deficiencies in them can exaggerate the underlying muscle weakness.
  • Many patients can have normal intellectual ability and hence require support in the form of psychologists and psychiatrists to help them deal with the stress of chronic disease.
  • (B3)

Differential Diagnosis

Differential diagnosis of patients presenting with weakness in early infancy includes: 

  1. Congenital myopathies – most common ones are central core, nemaline road, and centronuclear myopathy. These may also present secondary to metabolic disorders affecting the metabolism of carbohydrates, fats, and other molecules.
  2. Disorders of the myoneural junction – these are very infrequent in occurrence but should be part of differential diagnosis of infants presenting with weakness. These include congenital myasthenia gravis and infant botulism.
  3. Neuropathies – these are disorders primarily affecting nerve roots in the spinal cord and peripheral nerves. Common neuropathies presenting in early childhood include spinal muscular atrophy (SMA) and hereditary motor sensory neuropathy (HMSN).


Since the treatment of most of these disorders is supportive, long term prognosis is poor, and life expectancy depends on the correlation between the underlying genetic defect and phenotype secondary to the abnormal protein. The most common cause of morbidity and mortality in these disorders is secondary to respiratory or cardiac complications due to muscle weakness.



Chronic respiratory failure secondary to muscle weakness often leads to atelectasis, aspiration, and pneumonia secondary to mechanical ventilation.


Cardiomyopathy can be common comorbidity, and they can have chronic heart failure, which can require medical therapy.


They can have scoliosis due to immobility, osteopenia, and increased risk of fractures. Pressure ulcers and joint contractures may also develop, even despite aggressive physical therapy.


Adrenal insufficiency is common in these patients, and they may require steroid supplementation in case of stress. Thyroid and vitamin D levels should also be assessed as a part of the comprehensive evaluation.


Some of these patients can have seizures; the burden of psychological disorders like depression and anxiety is high in these patients due to underlying chronic disease.

Pearls and Other Issues

  1. Early diagnosis is the key to the management of these disorders, and if there is a prior family history, antenatal testing with DNA analysis in the pregnant female may be considered.
  2. A neurologist should see any infant presenting with unexplained muscle weakness, and genetic testing should be a part of the comprehensive evaluation since many of these disorders can have overlapping features.
  3. Establishing a confirmed genetic diagnosis is essential for prognostication, counseling, and prenatal testing for future pregnancies.

Enhancing Healthcare Team Outcomes

An interprofessional team should be involved in the care of these patients soon after the diagnosis is made as they can have multiple medical and psychosocial issues. The caregivers should be well trained to take care of the medical equipment that these patients require at home, like ventilators and feeding tubes. Regular follow up is required to address any underlying issues quickly, and this can improve the quality of life of these patients.



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