Muscular dystrophies are caused by mutations in genes that are important for muscle health. These mutations may be inherited — passed from parents to their biological children — or they can occur de novo (spontaneously) in an individual.
There are more than 30 different types of muscular dystrophy, each of which is caused by mutations in particular genes.
Duchenne and Becker muscular dystrophy
This gene provides instructions for making a protein called dystrophin, which functions like a sort of shock absorber for muscle cells, helping to protect the muscles from being damaged by the mechanical stresses of movement. When the DMD gene is mutated, not enough functional dystrophin protein is produced, so muscle cells become damaged.
In Duchenne, mutations usually lead to no or virtually no functional dystrophin protein being produced. With Becker, some dystrophin is usually produced, but either the protein doesn’t work quite right or not enough of it is made to properly maintain muscle health.
The DMD gene is located on the X chromosome, which is one of the two sex-determining chromosomes — with rare exceptions, females have two X chromosomes, while males have one X and one Y chromosome. Both DMD and BMD are more common in males because a healthy version of the DMD gene on the second X chromosome of females can compensate for the mutated gene.
Facioscapulohumeral muscular dystrophy
Facioscapulohumeral muscular dystrophy (FSHD) is caused by alterations in the D4Z4 region, which is a section of DNA located at the end of chromosome 4. Sometimes, this region of DNA is altered because of defects in other genes, such as SMCHD1 or DNMT3B.
FSHD is inherited in an autosomal dominant manner, meaning that just one mutated version of chromosome 4 (of the two inherited, one from each biological parent) is sufficient to cause the disease.
Limb-girdle muscular dystrophy
Limb-girdle muscular dystrophy (LGMD) mainly affects muscles in the shoulders and hips. There are several types of LGMD caused by mutations in different genes that are important for muscle health, including LMNA, CAV3, CAPN3, and DYSF. The mode of inheritance depends on the specific type of LGMD and the gene affected.
Oculopharyngeal muscular dystrophy
Oculopharyngeal muscular dystrophy (OPMD) primarily causes problems with the muscles around the eyes and in the throat. It is caused by mutations in a gene called PABPN1, which provides instructions for making a protein that helps to process messenger RNA (mRNA), an intermediary molecule made as a cell “reads” genes to make proteins.
OPMD is usually inherited in an autosomal dominant pattern, meaning that just one gene copy needs to be mutated in order for the disease to develop. Some people have mutations in both copies of the gene (one inherited from each biological parent), and they reportedly have more severe disease.
Tibial muscular dystrophy
Tibial muscular dystrophy (TMD), which primarily affects the lower legs, is caused by mutations in the TTN gene. This gene provides instructions for making a protein called titin, which is an essential component of sarcomeres — the basic structure that muscle cells use to contract.
TMD is inherited in an autosomal dominant pattern.
Myotonic muscular dystrophy
Myotonic dystrophy type 1 (DM1) is caused by mutations in a gene called DMPK. Myotonic dystrophy type 2 (DM2) is a rarer and caused by mutations in another gene, CNBP. These mutations lead to the production of an abnormal form of mRNA when the gene is “read,” which disrupts cellular functions.
Both DM1 and DM2 are inherited in an autosomal dominant manner.
Emery-Dreifuss muscular dystrophy
Emery-Dreifuss muscular dystrophy (EDMD) can be caused by mutations in one of three genes — EMD, FHL1, or LMNA.
Mutations in EMD and FHL1 are inherited in an X-linked recessive pattern, similar to mutations in DMD that cause Duchenne and Becker muscular dystrophies.
Most mutations in LMNA are inherited in an autosomal dominant pattern. More rarely, some LMNA mutations can be inherited in an autosomal recessive pattern, where both copies must be mutated for the disease to develop.
Congenital muscular dystrophies
Congenital muscular dystrophies are a group of muscular dystrophies where symptoms and signs are present at or near to birth. There are several types with different causes.
Bethlem myopathy is caused by mutations in the genes COL6A1, COL6A2, or COL6A3, all of which provide instructions for making a structural protein called type VI collagen. Most cases are inherited in an autosomal dominant manner, though rarer autosomal recessive cases have been reported.
Ullrich congenital muscular dystrophy is a more severe disease type that also is caused by mutations in the type VI collagen genes COL6A1, COL6A2, or COL6A3. This type usually is inherited in an autosomal recessive manner, though autosomal dominant cases have occurred.
Fukuyama congenital muscular dystrophy is caused by mutations in the FKTN gene, which provides instructions for making a protein called fukutin. Though this protein’s role is yet to be fully understood, research indicates that it is needed to add sugar molecules to another protein called alpha-dystroglycan, which is important for stabilizing and protecting muscles. Fukuyama congenital muscular dystrophy is inherited in an autosomal recessive pattern, and almost exclusively in Japanese populations.
Muscle-eye-brain disease or MEB is caused by mutations in another gene that’s important for alpha-dystroglycan synthesis, called POMGnT1. MEB is inherited in an autosomal recessive manner.
Walker-Warburg syndrome (WWS) also is caused by mutations in genes that affect the production of alpha-dystroglycan. At least a dozen individual genes have been linked to WWS, whose inheritance follows an autosomal recessive pattern.
About 40% of all cases of rigid spine muscular dystrophy (RSMD) are caused by mutations in the SELENON gene, which codes for a protein called selenoprotein N that is believed to be important for muscle formation and function. In the remaining cases, the genetic cause of RSMD is unknown. This type of muscular dystrophy is inherited in an autosomal recessive pattern.
Last updated: Dec. 20, 2021, by Marisa Wexler MS
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