Congenital muscular dystrophies

Emma Clement MD (Dr. Clement of Great Ormond Street Children's Hospital has no relevant financial relationships to disclose.)
Heinz Jungbluth MD PhD (Dr. Jungbluth of King's College London has no relevant financial relationships to disclose.)
Emma Ciafaloni MD, editor. (

Dr. Ciafaloni of the University of Rochester received personal compensation for serving on advisory boards and/or as a consultant for Avexis, Biogen, Pfizer, PTC Therapeutics, Sarepta, Ra pharma, Wave, and Strongbridge Biopharma; and for serving on a speaker’s bureau for Biogen. Dr Ciafaloni also received research and/or grant support from Orphazyme, PTC Therapeutics, Santhera, and Sarepta.

Originally released August 7, 2004; last updated October 2, 2018; expires October 2, 2021

This article includes discussion of congenital muscular dystrophies, laminin alpha 2-deficient congenital muscular dystrophy (MDC1A, merosin-deficient congenital muscular dystrophy type 1A), collagen VI-related MCD (Ullrich congenital muscular dystrophy, Bethlem myopathy), integrin-related congenital muscular dystrophy, dystroglycanopathy (Walker-Warburg, muscle-eye-brain disease, Fukuyama congenital muscular dystrophy, congenital muscular dystrophy with intellectual disability, congenital muscular dystrophy without intellectual disability, MDC1C, MDC1D, MDDGA1-14), CDG 1e (DPM1-related), CDG 1u (DPM2-related), CDG 1o (DPM3-related), CDG 1m (DOLK-related), rigid spine muscular dystrophy (RSMD1, SEPN1-related congenital muscular dystrophy), ACTA1-related congenital muscular dystrophy, Emery-Dreifuss muscular dystrophy type 2 (EDMD2, lamin A/C-related congenital muscular dystrophy), congenital muscular dystrophy with adducted thumbs (nesprin-related congenital muscular dystrophy), megaconial congenital muscular dystrophy (CHKB-related congenital muscular dystrophy), congenital muscular dystrophy 1C, congenital muscular dystrophy type 1C, dystrophia muscularis congenita, Fukuyama congenital muscular dystrophy, integrin alpha7 deficiency, laminin alpha2 deficient congenital muscular dystrophy, merosin-deficient congenital muscular dystrophy, muscle-eye-brain disease, muscle-eye-brain syndrome, muscular dystrophy congenital type 1A, muscular dystrophy congenital type 1C, muscular dystrophy congenital type 1D, rigid spine muscular dystrophy 1, rigid spine syndrome, and type II lissencephaly: cobblestone lissencephaly. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


The congenital muscular dystrophies are a heterogeneous group of inherited, mostly autosomal recessive disorders. The clinical features range from severe life-limiting disorders, often associated with brain involvement, to milder conditions with survival into adult life. Advances in understanding the genetic basis of congenital muscular dystrophies have significantly improved our understanding of their pathogenesis and clinical diversity. 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 dystrophies phenotypes and this number is likely to continue to rise with increasing availability 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 (Dubowitz 1994; Dubowitz 1996; Dubowitz 1997; Dubowitz 1999; Muntoni and Guicheney 2002; Muntoni et al 2002a; Muntoni et al 2003; Muntoni et al 2005; Muntoni et al 2009; Bonnemann et al 2010; Bonnemann et al 2011; Saunier et al 2016). Workshop reports can be accessed at A comprehensive historical review can be found in Voit and Tome 2004 (Voit and Tome 2004).

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 cases with clear CNS involvement (Dubowitz 1994). As our understanding of the biochemical and molecular basis of these conditions has progressed, a classification has evolved based on the primary biochemical defect (Muntoni and Voit 2004; Bonnemann et al 2014). This is summarized below and more comprehensively in Table 1.

Table of congenital muscular dystrophy variants with known gene defects Image: Congenital muscular dystrophy variants with known gene defects (table)


(1) 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


(2) Congenital muscular dystrophies resulting from abnormal glycosylation of alpha dystroglycan: a very 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.


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


(a) CDG 1e (DPM1-related)


(b) CDG 1u (DPM2-related)


(c) CDG 1o (DPM3-related)


(d) CDG 1m (DOLK-related)


(4) 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) TRAPPC11- related CMD

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