Disease and Inheritance Gene and Locus Clinical Findings Pathologic Findings

Facioscapulohumeral muscular dystrophy;

autosomal-dominant

Type 1A—deletion of variable number

of 3.3-kB subunits of a tandemly

arranged repeat (D4Z4) on 4q35

Variable age at onset (most commonly 10–

30 years); Weakness of muscles of face,

neck, and shoulder girdle

Dystrophic myopathy, but also often including

inflammatory infiltrates of muscle.

Type 1B (FSHMD1B)—locus unknown

Oculopharyngeal muscular dystrophy;

autosomal-dominant

Poly(A)-binding protein-2 (PABP2)

gene; 14q11.2-q13

Onset in midadult life; ptosis and weakness

of extraocular muscles; difficulty in

swallowing

Dystrophic myopathy, but often including

rimmed vacuoles in type 1 fibers

Emery-Dreifuss muscular dystrophy; Xlinked

(mostly)

Emerin (EMD1) gene; Xq28 Variable onset (most commonly 10–20

years); prominent contractures, especially of

elbows and ankles

Mild myopathic changes; absent emerin by

immunohistochemistry

Congenital muscular dystrophies; autosomalrecessive

(Also called muscular dystrophy,

congenital, subtypes MDC1A, MDC1B,

MDC1C)

Type 1A (merosin-deficient type)—

laminin a2 (merosin) gene; 6q22-q23

Neonatal hypotonia, respiratory

insufficiency, delayed motor milestones

Variable fiber size and extensive endomysial

fibrosis

Type 1B—locus at 1q42; gene unknown

Type 1C; fukutin-related protein gene;

19q13.3

muscle groups, and the specific diagnosis is based largely on the pattern of clinical muscle weakness ( Table 27-4 ). Several autosomal muscular dystrophies, however, affect the

proximal musculature of the trunk and limbs, similar to the X-linked muscular dystrophies, and are termed limb girdle muscular dystrophies.

Limb girdle muscular dystrophies are inherited in either an autosomal-dominant (type 1) or an autosomal-recessive (type 2) pattern ( Table 27-5 ). Six subtypes of the dominant

dystrophies (1A to 1F) and ten subtypes of the recessive limb girdle dystrophies (2A to 2J) have been identified. Mutations of the sarcoglycan complex of proteins have been identified

in four of the limb girdle muscular dystrophies[52] (2C, 2D, 2E, and 2F). These membrane proteins interact with dystrophin through another transmembrane protein, b-dystroglycan ( Fig.

27-10 ).

Myotonic Dystrophy

Myotonia, the sustained involuntary contraction of a group of muscles, is the cardinal neuromuscular symptom in this disease.[53] Patients often complain of "stiffness" and have

difficulty in releasing their grip, for instance, after a handshake. Myotonia can often be elicited by percussion of the thenar eminence.

Pathogenesis.

Inherited as an autosomal-dominant trait, the disease tends to increase in severity and appear at a younger age in succeeding generations, a phenomenon termed anticipation. Myotonic

dystrophy is associated with a trinucleotide CTG repeat expansion on chromosome 19q13.2-13.3. This expansion affects the mRNA for the dystrophila myotonia-protein kinase (DMPK).

[54] In normal subjects, fewer than 30 repeats are present; disease develops with expansion of this repeat, and in severely affected individuals, several thousand repeats may be present.

[54] The mutation is not stable within a pedigree; with each generation, more repeats accumulate, and this appears to correspond to the clinical

TABLE 27-5-- Limb Girdle Muscular Dystrophies

Date: 2016-04-22; view: 940