Congenital Muscular Dystrophy (CMD)

Types Of Congenital MD

There are more than 30 types of congenital muscular dystrophy (CMD). Although they can present differently, they all begin early in life, usually at birth or in infancy, and are caused by genetic changes that affect how muscle cells function.

Today, CMDs are classified mainly by their genetic cause and how the defect affects muscle cells. They are best understood as a group of disorders caused by defects in:

• Extracellular matrix proteins (such as LAMA2 and collagen VI), which help support and anchor muscle cells
• Glycosylation pathways (α-dystroglycanopathies), which affect how muscle cells attach to their surrounding support system
• Intracellular or structural proteins (such as SELENON and PLEC), which help muscle cells function properly from within
• Nuclear envelope proteins (such as LMNA), which help maintain the structure of the cell nucleus
• Metabolic pathways (such as CHKB), which are important for energy use and normal muscle function

Types of congenital muscular dystrophies

Congenital muscular dystrophies (CMDs) are a group of inherited muscle disorders that begin at birth or in early infancy. They cause muscle weakness and low muscle tone (hypotonia). Many people also develop joint contractures or joint looseness, and some have problems involving the brain, eyes, heart, or breathing muscles.

Most CMDs are inherited in an autosomal recessive pattern, but some forms can be dominant.

Today, CMDs are classified mainly by their genetic cause and how the defect affects muscle cells, rather than just symptoms. They are best understood as a group of disorders caused by defects in:

• Extracellular matrix proteins (e.g., LAMA2, collagen VI)
• Glycosylation pathways (α-dystroglycanopathies)
• Intracellular/structural proteins (e.g., SELENON, PLEC)
• Nuclear envelope proteins (LMNA)
• Metabolic pathways (CHKB)

CMDs affecting the extracellular matrix (muscle support structure)

LAMA2-related CMD (MDC1A; merosin-deficient CMD)

• Cause: LAMA2 mutations
• Features: Severe weakness from birth, delayed motor development, contractures (muscle/joint tightness), scoliosis, breathing problems
• Cognition: Usually normal
• Inheritance: Recessive

Collagen VI–related dystrophies (Ullrich CMD and Bethlem myopathy spectrum)

• Genes: COL6A1, COL6A2, COL6A3
• Features: Weakness, contractures + joint hyperlaxity (movement beyond the normal range of motion), soft skin, early respiratory problems
• Inheritance: Dominant or recessive

α-Dystroglycanopathies (glycosylation defects)

These are caused by problems in glycosylation of α-dystroglycan, affecting muscle, brain, and eyes.

• Range of severity:
  • Mild limb-girdle weakness
  • Fukuyama CMD
  • Muscle–eye–brain disease
  • Walker–Warburg syndrome (most severe)
• Common genes: FKRP, FKTN, POMT1, POMT2, POMGNT1, LARGE1, and others
• General features:
  • Muscle weakness from birth
  • Brain abnormalities, seizures
  • Eye involvement
  • Developmental delay/intellectual disability
• Other related forms:
  • INPP5K-related CMD: weakness, cataracts, short stature, mild–moderate intellectual disability

CMDs due to intracellular or structural protein defects

SELENON-related myopathy (formerly SEPN1-related)

• Features: Early weakness, rigid spine, significant breathing problems
• Cognition: Normal

Integrin α7 deficiency

• Gene: ITGA7
• Features: Congenital weakness, delayed walking, usually milder

Plectin-related CMD

• Gene: PLEC
• Features: Muscle weakness with skin blistering (epidermolysis bullosa), possible heart involvement

CMDs with nuclear envelope defects

LMNA-related CMD

• Gene: LMNA
• Features: Early weakness, rigid spine, cardiac arrhythmias and cardiomyopathy
• Inheritance: Usually dominant

CMDs with metabolic or mitochondrial-related defects

CHKB-related CMD

• Features: Early weakness, muscle wasting, intellectual disability, cardiomyopathy

Other related or overlapping conditions

Some disorders may overlap with CMD but are sometimes classified separately:

• RYR1-related disorders: can present like CMD but are often grouped with congenital myopathies
• DOK7-related conditions: primarily affect the neuromuscular junction (congenital myasthenic syndromes) rather than true CMD

Additional reading

• Pasrija D, Tadi P. Congenital Muscular Dystrophy. [Updated 2023 Jul 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558956/
• Bönnemann CG, Wang CH, Quijano-Roy S, Deconinck N, Bertini E, Ferreiro A, Muntoni F, Sewry C, Béroud C, Mathews KD, Moore SA, Bellini J, Rutkowski A, North KN; Members of International Standard of Care Committee for Congenital Muscular Dystrophies. Diagnostic approach to the congenital muscular dystrophies. Neuromuscul Disord. 2014 Apr;24(4):289-311. doi: 10.1016/j.nmd.2013.12.011. Epub 2014 Jan 9. PMID: 24581957; PMCID: PMC5258110.
• Zambon AA, Muntoni F. Congenital muscular dystrophies: What is new? Neuromuscul Disord. 2021 Oct;31(10):931-942. doi: 10.1016/j.nmd.2021.07.009. Epub 2021 Jul 28. PMID: 34470717.

Last reviewed June 2026.