Duchenne
muscular dystrophy (DMD) is the most common childhood form of muscular
dystrophy; it generally affects only boys (with extremely rare
exceptions), becoming clinically evident when a child begins walking. By
age 10, the child may need braces for walking and by age 12, most patients
are unable to walk. Life span ranges from 15 to 45 max. But there are a
few exceptions. In the early 1990s, researchers identified the gene for
the protein dystrophin which, when absent, causes DMD. The amount of
dystrophin correlates with the severity of the disease (i.e., the less
dystrophin present, the more severe the phenotype). Since the gene is on
the X chromosome, this disorder affects primarily males, and females who
are carriers have milder symptoms. Sporadic mutations in this gene occur
frequently, accounting for a third of cases. The remaining two-thirds of
cases are inherited in a recessive pattern.
Becker
muscular dystrophy (BMD) is a less severe variant of Duchenne
muscular dystrophy and is caused by the production of a truncated, but
partially functional form of dystrophin. Survival is usually into old age.
Affects only boys (with extremely rare exceptions)
Congenital
muscular dystrophy includes several disorders with a range of symptoms.
Muscle degeneration may be mild or severe. Problems may be restricted to
skeletal muscle, or muscle degeneration may be paired with effects on the
brain and other organ systems. A number of the forms of the congenital
muscular dystrophies are caused by defects in proteins that are thought to
have some relationship to the dystrophin-glycoprotein complex and to the
connections between muscle cells and their surrounding cellular structure.
Some forms of congenital muscular dystrophy show severe brain
malformations, such as lissencephaly and hydrocephalus.
Distal
muscular dystrophies' age at onset: 20 to 60 years; symptoms include
weakness and wasting of muscles of the hands, forearms, and lower legs;
progress is slow and not life-threatening. Miyoshi myopathy, one of the
distal muscular dystrophies, causes initial weakness in the calf muscles,
and is caused by defects in the same gene responsible for one form of LGMD
(Limb Girdle
Muscular Dystrophy).
Emery-Dreifuss
Muscular Dystrophy patients normally present in childhood and the early
teenage years with contractures. Clinical signs include muscle weakness
and wasting, starting in the distal limb muscles and progressing to
involve the limb-girdle muscles. Most patients also suffer from cardiac
conduction defects and arrhythmias which, if left untreated, increase the
risk of stroke and sudden death. There are three subtypes of Emery-Dreifuss
Muscular Dystrophy, distinguishable by their pattern of inheritance:
X-Linked, autosomal dominant and autosomal recessive. The X-linked form is
the most common. Each type varies in prevalence and symptoms. The disease
is caused by mutations in the LMNA gene, or more commonly, the EMD gene.
Both genes encode for protein componenets of the nuclear envelope.
However, how these mutations cause the pathogenesis is not well
understood.
Facioscapulohumeral
muscular dystrophy (FSHD) initially affects the muscles of the face,
shoulders, and upper arms with progressive weakness. Symptoms usually
develop in the teenage years. Some affected individuals become severely
disabled. The pattern of inheritance is autosomal dominant, but there are
a significant number of spontaneous mutations. Seminal research published
in August 2010 documents that two defects are needed for FSHD, which for
the first time provides a unifying theory for the underlying genetics of
FSHD. The first is the deletion of D4Z4 repeats and the second is a "toxic
gain of function" of the DUX4 gene. Facioscapulohumeral muscular dystrophy
(FSHD) occurs both in males and females.
Limb-girdle
muscular dystrophy is also called LGMD. Affects both boys and girls. LGMDs
all show a similar distribution of muscle weakness, affecting both upper
arms and legs. Many forms of LGMD have been identified, showing different
patterns of inheritance (autosomal recessive vs. autosomal dominant). In
an autosomal recessive pattern of inheritance, an individual receives two
copies of the defective gene, one from each parent. The recessive LGMDs
are more frequent than the dominant forms, and usually have childhood or
teenage onset. The dominant LGMDs usually show adult onset. Some of the
recessive forms have been associated with defects in proteins that make up
the dystrophin-glycoprotein complex. Though a person normally leads a
normal life with some assistance, in some extreme cases, death from LGMD
occurs due to cardiopulmonary complications.
Myotonic
muscular dystrophy is an autosomal dominant condition that presents with
myotonia (delayed relaxation of muscles) as well as muscle wasting and
weakness. Myotonic dystrophy varies in severity and manifestations and
affects many body systems in addition to skeletal muscles, including the
heart, endocrine organs, eyes, and gastrointestinal tract.
Myotonic
muscular dystrophy type 1 (DM1), also known as Steinert disease, is the
most common adult form of muscular dystrophy. It results from the
expansion of a short (CTG) repeat in the DNA sequence of the DMPK (myotonic
dystrophy protein kinase) gene. Myotonic muscular dystrophy type 2 (DM2)
is much rarer and is a result of the expansion of the CCTG repeat in the
ZNF9 (zinc finger protein 9) gene. While the exact mechanisms of action
are not known, these molecular changes may interfere with the production
of important muscle proteins.
Oculopharyngeal
MD's age at onset: 40 to 70 years; symptoms affect muscles of eyelids,
face, and throat followed by pelvic and shoulder muscle weakness, has been
attributed to a short repeat expansion in the genome which regulates the
translation of some genes into functional proteins.
* Information from various sources on the
internet. Any suggested corrections are welcome. |