TABLE 21-5
Inherited Diseases o f Muscle
Description
Hypertrophic cardiomyopathy
Dyspnea, chest pain or syncope, usually features ventricular hypertrophy with impingement
on LV volume and often LV outflow obstruction. Most cases hereditary, but some are new
mutations. Defective genes for /3-MHC, either MLC, TnT, Tnl, oc-tropomyosin, myosin
binding protein C.
Muscular dystrophy
Duchene
(DMD) and
Becker’s
(BMD) muscular dystrophy. Progressive number and
severity of lesions in muscle fibers leading to inflammation and rapid (DMD) or slow
(BMD) loss of fibers. DMD due to deletion of most or all of the gene for dystrophin, BMD
due to defective dystrophin. See text.
Limb girdle
(Erb’s disease) Either pelvic or shoulder girdle initially,with spread to the
other. Variable progression.
Facioscapulohumeral
(Lou Gehrig’s disease) Face and shoulder girdle initially, then
pelvic girdle and legs. Progression usually slow.
Distal
Onset in extremities, progresses proximally. Usually slow progression.
Ocular
External ocular muscles, some involvement of face, neck, arms.
Oculopharyngeal
As in ocular, but with dysphagia.
Myotonic dystrophy
(Steinert’s disease) Muscle stiffness and impaired relaxation after
contraction, wasting of muscles of face, neck, distal limbs, many other serious symptoms.
Defect in gene coding for a serine-threonine kinase, resulting in impaired Na-K ATPase
activity and perhaps other problems.
Metabolic diseases: Glycogen storage diseases (GSD)
GSD type II, Pompe’s disease
Deficiency of acid maltase causes excess glycogen
accumulation in lysosomes. See text.
GSD type III, Cori’s disease
Deficiency of debranching enzyme activity causes accumu-
lation of limit dextrins. See text.
GSD type V, McArdle’s disease
Myophosphorylase deficiency, inability to utilize glycogen.
See text.
GSD type VII, Tarui’sdisease
Muscle phosphofructokinase deficiency causes pronounced
decrease in exercise tolerance.
Other metabolic diseases
Carnitine deficiency
Impaired
ß-
oxidation with lipid accumulation, see text
Adenylate deaminase deficiency
Impaired anaerobic tolerance.
Channelopathies
Myotonias
(muscle stiffness, impaired relaxation, fasciculation) due to various defects in
skeletal muscle chloride channel 1 (CLCN1 orCIC-l):
Becker’s generalized myotonia
(with moderate weakness and atrophy)
Myotonia levior
Thomsen’s myotonia congenita
(without weakness, may hypertrophy)
Central core storage disease
Abnormal SR with myofibrillar degeneration near fiber axis.
Due to RyRl gene defect.
Hypokalemic periodic paralysis
Due to defective gene for one type of DHPR.
Hyperkalemic periodic paralysis
Due to defects in a skeletal muscle sodium channel,
SCN4A.
Paramyotonia congenita
and
“pure” myotonias
Are due to varied (and different)
mutations in the gene for SCN4A.
Mitochondrial myopathy
Due to defects in mitochondrial genes.
Mitochondrial myopathy
Fiber degeneration, weakness, “ragged red fibers” histological
appearance.
CPEO (chronic progressive external opthalmoplegia)
Paralysis of eye muscles and
mitochondrial myopathy.
KSS (Kearns-Sayre syndrome)
CPEO plus retinal degeneration, cardiomyopathy,
hearing loss, diabetes, renal failure.
MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes)
Cognitive symptoms, seizures, transient paralysis, and mitochondrial myopathy.
Inheritance*
Most AD with
variable
penetrance
X-linked
recessive, or
new mutations
Usually AR,
maybe dominant
AD
AD
Most cases AD
AD
AD
AR
AR
AR
AR
AR
AR
AR
AD
AD
?
AD
AD
AD
See text
most cases tRNA
gene defects
*AD=Autosomal dominant, AR=autosomal recessive
