Congenital muscular dystrophy

Congenital muscular dystrophy (CMD) is the name of a group of muscle conditions in which there are about 30 known subtypes. Each type displays a common muscle weakness and hypotonia from birth or infancy. Joints can become progressively tight or fixed (contractures) and/or display an unusual laxity. CMD conditions are largely inherited and are linked to specific genes, variants in which result in muscles becoming more easily damaged from normal use; often combined with faulty repair systems, this results in a progressive worsening of signs and symptoms. There is a variable prognosis, and respiratory failure can cause early death.

CMD conditions display a wide variability in clinical phenotype, severity and progression. In certain types of CMD, additional body systems can be affected.

• Antenatal:
  • polyhydramnios linked to decreased swallowing; and
  • reduced fetal movements.
• Neonatal/infancy:
  • generalised hypotonia resulting in a floppy baby or infant;
  • poor suck and swallowing difficulties;
  • weak cry;
  • respiratory insufficiency due to muscle weakness;
  • variable contractures (tightness) or laxity of joints;
  • variable spinal effects (curvatures, rigidity); and
  • facial muscle involvement, such as ptosis and prolonged mouth opening.
• Childhood:
  • persistent hypotonia (may be proximal or distal);
  • developmental delay (particularly motor and ambulation delay, but global delays are also possible);
  • poor feeding and respiratory muscle weakness (aspirations, atelectasis, pneumonias);
  • contractures can lead to arthrogryposis, scoliosis, increased chance of fractures and pressure ulcers;
  • spinal rigidity (can have a variable onset in childhood);
  • facial muscle involvement, such as ptosis and prolonged mouth opening; and
  • variable presentations of:
    • intellectual and learning difficulties;
    • seizures and central nervous system involvement;
    • vision and ocular muscle problems; and
    • cardiac involvement.

There are many differentials to consider for a hypotonic infant, and it is important not to confuse congenital myotonic dystrophy with CMD.

There are more genes associated with CMD than previously thought, with some types attributed to pathogenic variants from more than one gene. A common way of categorising known CMD types is by the muscle protein that is primarily affected – see table 1 below.

Table 1: Summary of known CMD types (not exhaustive)

The genetic basis for CMD conditions is complex and wide ranging. For further information on genomic testing, see Presentation: Child with progressive muscle weakness or suspected muscular dystrophy.

There are a range of inheritance patterns found across the various subtypes of CMD, although most are autosomal recessive.

Most individuals affected by an autosomal recessive condition have parents who are carriers, which means that the parents have a 25% (one-in-four) chance of another child being affected.

When genomic testing reveals a pathogenic variant (or variants) in the child, parental carrier testing should be offered alongside genomic counselling around chance of recurrence.

Ulrich CMD can be inherited in both autosomal dominant and autosomal recessive patterns. LMNA-related CMD is predominantly caused by a dominant de-novo variant.

Management of CMD is complex and requires a multidisciplinary team approach to maximise supportive care for patients and their families. This team often consists of paediatric neurologists, paediatric orthopaedic surgeons, clinical geneticists, genetic counsellors, general practitioners, physiotherapists, occupational therapists, speech and language therapists and special educational needs teachers.

For clinicians

• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• NHS England: National Genomic Test Directory
• National Organisation for Rare Disorders: Congenital muscular dystrophy
• StatPearls: Congenital muscular dystrophy

References:

• Bönnemann CG, Wang CH, Quijano-Roy S and others. ‘Diagnostic approach to the congenital muscular dystrophies’. Neuromuscular Disorders 2014: volume 24, issue 4, pages 289–311.  DOI: 10.1016/j.nmd.2013.12.011

For patients

• Muscular Dystrophy Association: Congenital muscular dystrophy