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  • Updated 12.25.2023
  • Released 08.07.2004
  • Expires For CME 12.25.2026

Congenital muscular dystrophies



The congenital muscular dystrophies are a heterogeneous group of inherited, mostly autosomal recessive neuromuscular disorders. Clinical severity ranges from severe presentations with substantially shortened lifespan and frequent association with cerebral involvement, to milder forms with survival into adulthood. Major advances in the genetic understanding of congenital muscular dystrophies have broadened our knowledge of the clinical variability and pathogenesis of individual disorders. A classification of congenital muscular dystrophies combining clinical features and biochemical defects is now widely used. More than 25 genes are known to cause congenital muscular dystrophy phenotypes, and this number is likely to rise further with the decrease in cost of next-generation sequencing technology. Allelic mutations at most of the known loci can give rise to a wide spectrum of phenotypic severity.

Key points

• Congenital muscular dystrophy encompasses a group of conditions that presents at birth or within the first months of life with weakness, hypotonia, and delayed motor milestones. Contractures are a common feature, and mental retardation is seen in some.

• Skeletal muscle biopsy shows dystrophic change and additional immunohistochemical abnormalities of variable specificity. Some forms of congenital muscular dystrophy are associated with characteristic features on brain or muscle MRI.

• Congenital muscular dystrophy results from abnormalities in proteins of the muscle cell, usually components of the extracellular matrix, basal lamina, or external membrane. A further subgroup results from abnormalities in the posttranslational modification of the key external receptor alpha dystroglycan.

Historical note and terminology

Congenital muscular dystrophy was first described over a century ago by Frederick Eustace Batten. Progress in this field was relatively slow until the 1990s. Since this time, huge advances have been made with pathological and molecular characterization of many different subtypes of congenital muscular dystrophy. This has been facilitated to a large degree by the activity of the European Neuromuscular Centre (ENMC) Congenital Muscular Dystrophy Consortium, which convenes dedicated workshops on the subject (50; 124; 19; 162). Workshop reports can be accessed at A comprehensive historical review can be found in 195 (195).

The classification of congenital muscular dystrophy has historically been problematic due to the inherent heterogeneity of this group. The first attempt to formally classify congenital muscular dystrophies divided them into “classical” congenital muscular dystrophy without intellectual impairment or overt CNS changes and those with clear CNS involvement (50). As our understanding of the biochemical and molecular basis of these conditions has progressed, a classification has evolved based on the primary biochemical defect (127; 20). This is summarized below and more comprehensively in Table 1.

Congenital muscular dystrophy variants with known gene defects (table)
MDC1A, congenital muscular dystrophy Type 1A; UCMD, Ullrich congenital muscular dystrophy; BM, Bethlem myopathy; WWS, Walker-Warburg syndrome; MEB, muscle-eye-brain disease, FCMD, Fukuyama congenital muscular dystrophy; MDC1C,mero...

(I) Defects in the extracellular matrix, peripheral membrane, or basal lamina

(A) Laminin alpha 2-deficient congenital muscular dystrophy (MDC1A)

(B) Collagen VI-related congenital muscular dystrophy (Ullrich congenital muscular dystrophy and Bethlem myopathy)

(C) Collagen XII-related congenital muscular dystrophy

(D) Integrin-related congenital muscular dystrophy

(II) Congenital muscular dystrophies resulting from abnormal glycosylation of alpha dystroglycan: a heterogeneous group. Phenotypes are categorized by OMIM as MDDGA 1-14 and include Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy. Known genes include POMT1, fukutin, and FKRP. Refer to Table 1 for a full list.

(III) Congenital disorders of glycosylation with abnormal glycosylation of alpha dystroglycan

(A) Affecting the dolichol-P-mannose pathway

(i) CDG 1e (DPM1-related)
(ii) CDG 1u (DPM2-related)
(iii) CDG 1o (DPM3-related)
(iv) CDG 1m (DOLK-related)
(v) GMPPB; 3p21: MDDGA14

(B) Golgi related

(i) TRAPPC11-related congenital muscular dystrophy
(ii) GOSR2-related congenital muscular dystrophy
(iii) B3GNT1 (B4GAT1) [Glucuronate moiety]; 11q13: MDDGA13
(iv) TMEM5 [Xylose moiety]; 12q14: MDDGA10
(v) LARGE; 22q12: MDDGA6; MDDGB6

(IV) Intracellular and nuclear forms

(A) Rigid spine muscular dystrophy (RSMD1, SEPN1-related congenital muscular dystrophy)

(B) ACTA1-related congenital muscular dystrophy

(C) EDMD2 (Lamin A/C-related congenital muscular dystrophy)

(D) Congenital muscular dystrophy with adducted thumbs (nesprin-related congenital muscular dystrophy)

(E) Megaconial type congenital muscular dystrophy (choline kinase beta-related congenital muscular dystrophy)

(F) RYR1-related congenital muscular dystrophy

(G) PTRF-related PCGLP4 with congenital muscular dystrophy

(H) Congenital muscular dystrophy merosin-positive

(I) Congenital muscular dystrophy with adducted thumbs

(J) Congenital muscular dystrophy with cerebellar atrophy

(K) INPP5K-related muscular dystrophy

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