Muscular dystrophies are a heterogeneous group of hereditary illnesses affecting both children and adults, with at least 30 different genes responsible for the disease development. These conditions are characterized by muscle wasting and weakness and may be associated with cardiomyopathy with an increased risk of sudden cardiac death.
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Dystrophinopathies are muscle diseases caused by pathogenic variants in the gene DMD which encodes the protein dystrophin. The severe end of the spectrum includes two diseases that include Duchenne and Becker muscular dystrophy, whereas the mild end of the spectrum can manifest only with an increased serum concentration of creatine phosphokinase (CK), myoglobinuria, and occasional muscle cramps.
Duchenne muscular dystrophy represents a severe, progressive disease that affects 1 in 3,600–6,000 live male births. It is one of the most severe muscle diseases to affect children. The majority of patients are unable to run and jump adequately due to proximal muscle weakness, which also results in the use of the classic Gowers maneuver when arising from the floor.
Muscle weakness in Duchenne muscular dystrophy can begin as early as in the fourth year of life, initially affecting the pelvic area, hip muscles, thighs, and shoulders. By the early teenage years, the heart and respiratory muscles are also affected. The disease is rapidly progressive, with affected children being wheelchair dependent by the age of 13.
Becker muscular dystrophy is usually milder and more varied as compared to Duchenne muscular dystrophy. In most cases, muscle weakness becomes obvious later in childhood or in adolescence, and muscle deterioration occurs at a much slower rate. This type of muscular dystrophy occurs in about 3 to 6 out of every 100,000 live male births.
Congenital muscular dystrophy
Congenital muscular dystrophies represent a mixed group of conditions with varying degrees of severity and progression rates. These conditions are characterized by diminished muscle tone at birth, otherwise known as congenital hypotonia, delayed motor development, spinal rigidity, early onset of progressive muscle weakness, and dystrophic pattern on muscle biopsy.
Congenital muscular dystrophy
The main subtypes of congenital muscular dystrophy, which are grouped according to the involved protein function and mutated gene, are laminin alpha-2 (or merosin) deficiency, collagen VI-deficient congenital muscular dystrophy, the dystroglycanopathies, SEPN1-related congenital muscular dystrophy, and LMNA-related congenital muscular dystrophy. Several lesser-known subtypes have also been reported in a small number of individuals.
Cognitive impairment that ranges from intellectual disability to mild cognitive delay, structural eye and brain abnormalities, as well as seizures, are almost exclusively found in dystroglycanopathies. Comparatively, white matter abnormalities without major cognitive involvement are usually seen in the laminin alpha-2-deficient subtype.
Myotonic dystrophy and other types
Myotonic dystrophy is considered the most common adult form of muscular dystrophy. Moreover, this form of muscular dystrophy is characterized by autosomal dominant progressive myopathy, myotonia, and the involvement of multiple organs. To date, two distinct forms of myotonic dystrophy caused by similar mutations have been identified, which require different diagnostic and management strategies despite their clinical and genetic similarities.
Other types of muscular dystrophy that can occur later in life include limb-girdle muscular dystrophy, distal muscular dystrophy, and ophthalmoplegic muscular dystrophy. The severity, age of onset, and features of these conditions vary significantly among the many subtypes, and may also be inconsistent even within the same family.
Facioscapulohumeral dystrophy is a form of muscular dystrophy that affects the face and shoulders. It is generally considered more benign than other forms of muscular dystrophy. Most cases arise due to a deletion near the end of chromosome 4, and symptoms develop in the teenage years.