Disease and Inheritance Gene and Locus Clinical Findings Pathologic Findings

Central core diseases; autosomaldominant

Ryanodine receptor-1 (RYR1) gene;

19q13.1

Early-onset hypotonia and nonprogressive

weakness; associated skeletal deformities; may

develop malignant hyperthermia

Cytoplasmic cores are lightly eosinophilic and distinct

from surrounding sarcoplasm; Found only in type 1

fibers, which usually predominate, best seen on

NADH stain

Nemaline myopathy; autosomaldominant

or autosomal-recessive

Autosomal-dominant (NEM1)—

Tropomyosin 3 (TPM3) gene;

Autosomal-recessive (NEM2)—

nebulin (NEB) gene; 2q22

Weakness, hypotonia, and delayed motor

development in childhood; may also be seen in

adults; usually nonprogressive; involves

proximal limb muscles most severely; skeletal

abnormalities may be present

Aggregates of subsarcolemmal spindle-shaped

particles (nemaline rods); occur predominantly in type

1 fibers; derived from Z-band material (a-actinin) and

best seen on modified Gomori stain

Autosomal-dominant or recessive—

skeletal muscle actin, a chain

(ACTA1) gene; 1q42.1

Myotubular (centronuclear)

myopathy; X-linked (MTM1),

autosomal-recessive, or autosomaldominant

X-linked—myotubularin (MTM1)

gene; Xq28

X-linked form presents in infancy with

prominent hypotonia and poor prognosis;

autosomal forms have limb weakness and are

slowly progressive; autosomal-recessive form

is intermediate in severity and prognosis

Abundance of centrally located nuclei involving the

majority of muscle fibers; central nuclei are usually

confined to type 1 fibers, which are small in diameter,

but can occur in both fiber types

Autosomal-dominant—myogenic

factor 6 (MYF6) gene; 12q21

Autosomal-recessive—locus and gene

unknown

Malignant hyperpyrexia (malignant hyperthermia) is a rare clinical syndrome characterized by a dramatic hypermetabolic state (tachycardia, tachypnea, muscle spasms, and later

hyperpyrexia) triggered by the induction of anesthesia, usually with halogenated inhalational agents and succinylcholine. The clinical syndrome may also occur in predisposed

individuals with hereditary muscle diseases, including congenital myopathies, dystrophinopathies, and metabolic myopathies. The only reliable method of diagnosis is contraction of

biopsied muscle on exposure to anesthetic. Mutations in different genes have been identified in families with susceptibility to malignant hyperthermia, including genes encoding a

voltage-gated calcium channel (lq32), an L-type voltage-dependent calcium channel (7q21-q22), and a ryanodine receptor (19q13.1).[59]

Figure 27-12 A, Nemaline myopathy with numerous rod-shaped, intracytoplasmic inclusions (dark purple structures). B, Electron micrograph of subsarcolemmal nemaline bodies,

showing material of Z-band density.

Figure 27-13 A, Mitochondrial myopathy showing an irregular fiber with subsarcolemmal collections of mitochondria that stain red with the modified Gomori trichrome stain (ragged

red fiber). B, Electron micrograph of mitochondria from biopsy specimen in A showing "parking lot" inclusions.

Figure 27-14 A, Dermatomyositis. Note the rash affecting the eyelids. B, Dermatomyositis. The histologic appearance of muscle shows perifascicular atrophy of muscle fibers and

inflammation. C, Inclusion body myositis showing a vacuole within a myocyte. (Courtesy of Dr. Dennis Burns, Department of Pathology, University of Texas Southwestern Medical

School, Dallas, TX.)

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