Congenital muscular dystrophy (CMD) refers to a heterogeneous group of inherited disorders in which weakness is first apparent at birth (congenital) or in infancy. Muscular dystrophies, in general, are genetic, degenerative diseases primarily affecting voluntary muscles. Most forms are inherited in an autosomal recessive manner.
The severity of the condition, the associated signs and symptoms and the disease progression vary significantly by type. Common features include hypotonia; progressive muscle weakness and degeneration (atrophy); joint contractures; and delayed motor milestones (i.e. sitting up, walking, etc). CMD can affect body organs other than the muscles and bones. This leads to complications, and some can be life-threatening. The symptoms that result include breathing/lung problems, cardiac problems, feeding difficulties, trouble swallowing, including choking or breathing in food or fluid, problems with brain and eye formation, cognitive issues and seizures.
CMD can be caused by a variety of different genes. Most forms of CMD are inherited in an autosomal recessive pattern, but at least one form appears to follow a dominant pattern of inheritance. Autosomal recessive disorders are inherited through a defective gene from both parents. If both parents are carriers there is a 25% chance that each child will inherit both defective genes.
Classifications of congenital muscular dystrophy
1. Defects of structural proteins
- Merosin-deficient CMD (MDC1A); Lamininα2
- UCMD1; Collagen 6A1
- UCMD2; Collagen 6A2
- UCMD3; Collagen 6A3
- Integrin α7-deficient CMD; Integrin α7
- CMD with epidermolysis bullosa; Plectin
2. Defects of glycosylatio
- Walker-Walburg syndrome; multiple genes
- Muscle-eye brain disease, multiple genes
- Fukuyama CMD; Fukutin
- Other phenotypes associated with mutations in glycosyltransferase genes
3. Proteins of the endoplasmic reticulum and nucleus
- Rigid spine syndrome; Selenoprotein N, 1
- Rigid spine syndrome; Selenocysteine insertion sequence-binding protein 2
- LMNA-deficient CMD; Laminin A/C
4. Mitochondrial membrane protein
- CMD with mitochondrial structural abnormalities; Choline kinase beta
CMD affects males and females in equal numbers. The exact incidence and prevalence of CMD are unknown. One estimate based on findings within an Italian population place the incidence at 1 in 125,000. Another study placed the incidence in western Sweden at 1 in 16,000. However, these findings may not be applicable in other parts of the world. The muscular dystrophies as a whole are estimated to affect approximately 250,000 people in the United States. Some forms of CMD occur with greater frequency in certain parts of the world. Fukuyama CMD is found almost exclusively in Japan. MEB occurs with the greatest frequency in Finland. MDC1A is generally considered to be the most common form of CMD worldwide.
A diagnosis of CMD is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms, and a variety of specialized tests including surgical removal and microscopic examination (biopsy) of affected muscle tissue that may reveal characteristic changes to muscle fibers; a test that assesses the health of muscles and the nerves that control muscles (electromyography); specialized blood tests; tests that evaluate the presence and number of certain muscle proteins (immunohistochemistry); magnetic resonance imaging (MRI), and molecular genetic testing.
There is no cure for CMD. Treatment is tailored to an individual’s needs and is best managed by a multidisciplinary team. Speech therapy and swallowing studies are used to evaluate those with feeding difficulties and/or possible aspiration. Interventions may be needed for inadequate weight gain and poor feeding. Aspiration pneumonia and/or respiratory insufficiency may require assisted cough devices, supplemental oxygen, noninvasive ventilation, and/or mechanical ventilation via tracheostomy. Physical therapy focuses on stretching exercises of the spine and limbs and to prevent contractures, and positive pressure devices or ventilation to promote mobility of the thoracic cage. Splints, braces and surgical intervention are used to prevent and treat spinal and limb contractures and deformities; these and other assistive devices may help posture, ambulation, and mobility. Epilepsy, behavior problems, and/or intellectual disability require specific treatment and interventions. Vaccinations, early treatment of pulmonary infections, and attention to oral hygiene and care are important aspects of routine care. With support for their physical disabilities the vast majority of children with CMD who have normal cognitive development benefit socially and educationally from mainstreaming into regular educational facilities. The multidisciplinary team can provide social and emotional support for patients and caregivers.
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