What are congenital muscular dystrophies (CMDs)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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Congenital muscular dystrophies (CMD) are extremely rare and greatly heterogeneous neuromuscular disorders with onset at birth or early infancy, characterized by hypotonia, delayed motor development, and progressive weakness. The clinical presentation is variable and can affect other organs, including the eyes, brain, lungs, and heart. Serum creatine kinase (CK) is elevated in several cases but not all. Appropriate muscle biopsy studies are crucial for accurate diagnosis.

In 1903, Batten described 3 children who had proximal muscle weakness from birth. Biopsy of their muscles showed evidence of chronic myopathy without distinguishing characteristics. In 1908, Howard coined the term congenital muscular dystrophy (CMD) when he described another infant with similar features. Ullrich first described the combination of joint hyperlaxity and proximal contractures in 1930 in the German literature; this was the first case of what is now known as Ullrich congenital muscular dystrophy.

In 1960, Fukuyama et al described a common congenital muscular dystrophy in Japan that always had features of muscular dystrophy and brain pathology. [1] Other diseases involving the muscle, eye, and brain were subsequently described: a Finnish variant (originally called muscle-eye-brain disease and Walker-Warburg syndrome. As has become clear with molecular genetics, all of these CMDs are likely caused by a similar molecular pathologic event, abnormal glycosylation of α-dystroglycan.

In a study of 116 patients in the United Kingdom, the most common congenital muscular dystrophies were collagen VI-related disorders (19%), with α-dystroglycanopathy congenital muscular dystrophy (12%) and merosin-deficient congenital muscular dystrophy (MDC1A) (10%) being next in frequency. An Australian study in 2008 showed dystroglycanopathy as the most common congenital muscular dystrophy (25%) on that continent, followed by collagen VI-related disorders (12%). Fukuyama congenital muscular dystrophy is the most prevalent form (49.2%) in Japan, followed by collagen VI deficiency at 7.2%. [1]

In general, CMDs are autosomal recessive diseases resulting in severe proximal weakness at birth (or within the first 12 mo of life) that is either slowly progressive or nonprogressive. Contractures are common, and CNS abnormalities can occur. Muscle biopsy shows signs of dystrophy, including a marked increase in endomysial and perimysial connective tissue; variability in fiber size with small, round fibers; immature muscle fibers; and (uncommonly) necrotic muscle fibers. No distinguishing features are present in muscle biopsy specimens, differentiating these disorders from the congenital myopathies.

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