Relatively benign congenital muscular dystrophy
usually beginning in childhood or adolescence and characterized by early
muscle contractures (mainly shoulders and upper arms) and cardiac conduction
Scapuloilioperoneal Atrophy with Cardiomyopathy.
No precise data are available. The X-linked form (males
only) is more frequent and has been reported in more than 70 families. The
estimated prevalence is approximately 1:100,000 in the general population.
The autosomal dominant form is much less frequent.
Two forms of EDMD exist: (1) X-linked,
resulting from a mutation in the emerin gene (>100 mutations have been
reported and mapped to X28q) that usually results in complete absence of
emerin from the muscles, and (2) autosomal dominant, resulting from a
mutation in the lamin A/C gene on 1q21. Lamins A/C are part of the nuclear
lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear
membrane, where they interact with chromatin and other proteins of the inner
nuclear membrane (lamina-associated proteins and emerin) through various
binding sites. Significant intrafamilial and interfamilial variability have
been described. Sporadic cases have been described.
Almost all known mutations result in a complete
absence of emerin, an inner nuclear membrane protein not limited to muscle
cells but mostly expressed in skeletal and cardiac muscles. It is believed
to interact with the nuclear lamins (components of the nuclear lamina),
chromatin, and nuclear actin. Its exact role is unknown, but it seems to
protect the nuclear membrane from mechanical lesions during muscle
contraction. It also may favor reassembly of the nuclear membrane at the end
of mitosis. Lamins A/C is also an inner nuclear membrane protein with
properties similar to emerin, which would account for the similarity in
phenotype between X-linked and autosomal dominant EDMD. For emerin (and
presumably lamins A/C) to function properly, the protein must be correctly
positioned on the nuclear membrane. Any defect in the nuclear membrane could
interfere with skeletal muscle regeneration because emerin seems to play an
important role in the organization of the nuclear membrane during cell
division. Emerin seems to be associated with cardiac desmosomes and fasciae
adherentes, which not only suggests a physiologic role for the protein in
cardiac function but also explains the cardiac involvement.
Mainly based on the clinical findings. It is easier to
diagnose if a relative has the disease. Serum creatinine kinase levels are
moderately increased. Electromyography and nerve conduction studies confirm
the myopathic nature of the disease. Muscle biopsy using antibodies to
emerin can help confirm the diagnosis in the X-linked form.
The two forms of the disorder are clinically
similar. Onset of the clinical manifestations usually occurs in the second
or third decade of life. The following triad characterizes the disorder. (1)
Early contractures affecting the Achilles tendons (resulting in toe
walking), elbows (biceps and triceps), and posterior cervical muscles
(initially resulting in limited cervical flexion, which later extends to the
whole spine) often occur before any muscle ...