Paeds · neurology-neurodisability-and-neuromuscular
Congenital myopathies and muscular dystrophies
Also known as Congenital muscular dystrophy · Congenital myopathy · Merosin-deficient congenital muscular dystrophy · Collagen VI-related dystrophy · Dystroglycanopathy · Central core disease · Nemaline myopathy · Centronuclear myopathy
Fellowship guide to congenital myopathies and muscular dystrophies in children. Covers the division into the dystrophic congenital muscular dystrophies and the structurally disordered congenital myopathies, the merosin-deficient LAMA2 form with its white matter changes and raised creatine kinase, the collagen VI spectrum of Ullrich and Bethlem with contractures and distal hyperlaxity, the dystroglycanopathies of Walker-Warburg and muscle-eye-brain disease with cobblestone lissencephaly and eye malformations, the LMNA and SEPN1 and titin forms, the congenital myopathies of central core disease with ryanodine receptor RYR1 mutations and malignant hyperthermia risk, nemaline myopathy with its rod bodies, and centronuclear myotubular myopathy with neonatal respiratory failure, the creatine kinase as the first fork, the brain and eye examination, the muscle biopsy findings of cores and rods and central nuclei, the multigene panel replacing biopsy, and the multidisciplinary management of respiratory support, nutrition, contractures, scoliosis, and rehabilitation.
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Red flags
- A floppy infant with weak suck and feeding difficulty and reduced or absent reflexes has a neuromuscular cause of hypotonia until proven otherwise, not a benign or behavioural one
- A creatine kinase over one thousand units per litre in a neonate or infant argues for a congenital muscular dystrophy and against a congenital myopathy, and it changes the gene panel and the prognosis
- A child with a collagen VI or SEPN1 or myotubular myopathy can walk yet still develop silent diaphragmatic respiratory failure, so forced vital capacity and sleep studies drive the decision to start non-invasive ventilation, not the walking ability
- Any child with an RYR1-related central core disease is at risk of malignant hyperthermia with volatile anaesthetics and succinylcholine, and the family must be flagged and a medic-alert issued before any anaesthetic
- Brain malformations with eye abnormalities and severe weakness point to a dystroglycanopathy such as Walker-Warburg syndrome, which carries a grim prognosis and needs urgent imaging and ophthalmology
- LMNA-related congenital muscular dystrophy carries a risk of cardiac conduction disease and sudden death even with preserved ejection fraction, so cardiac surveillance with echocardiography and Holter monitoring is mandatory from diagnosis
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- Recognises the floppy infant with weak suck, feeding difficulty, and reduced or absent reflexes as having a probable neuromuscular cause of hypotonia and states the creatine kinase as the first fork between a congenital muscular dystrophy and a congenital myopathy
- Identifies respiratory failure, feeding difficulty, contractures, and malignant hyperthermia risk as the key threats in congenital muscle disease
- Initiates multidisciplinary supportive care with respiratory monitoring, nutrition, and physiotherapy and refers to a paediatric neurology and neuromuscular service
- Distinguishes the dystrophic congenital muscular dystrophies from the structurally disordered congenital myopathies on creatine kinase, brain and eye findings, and muscle biopsy, and names the major genes LAMA2, COL6A, the dystroglycanopathy genes, LMNA, RYR1, NEB, and MTM1
- Applies the pattern of creatine kinase, white matter change, cobblestone lissencephaly, eye malformation, and contracture to target a next-generation sequencing panel
- Manages the respiratory, nutritional, orthopaedic, and cardiac complications and counsels the family on inheritance, prognosis, and prenatal diagnosis
- The creatine kinase fork: normal or mildly raised in congenital myopathies and markedly raised in congenital muscular dystrophies
- The merosin-deficient LAMA2 form with diffuse white matter changes and the dystroglycanopathies with cobblestone lissencephaly and eye malformations
- The malignant hyperthermia risk in RYR1 central core disease and the respiratory failure in myotubular and collagen VI and SEPN1 disease
- Runs the systematic assessment of the floppy infant, the creatine kinase, the brain and eye examination, and the targeted gene panel while starting respiratory and nutritional support
- Coordinates the multidisciplinary management of ventilation, gastrostomy, contracture and scoliosis surgery, and rehabilitation, and times the surveillance of forced vital capacity and cardiac function
- Counsels the family on the diagnosis, the inheritance pattern, the prognosis, and the reproductive options including prenatal and preimplantation diagnosis
- Level 1: Recognition of the floppy infant with weak suck and reduced reflexes as a probable neuromuscular cause of hypotonia requiring urgent creatine kinase and neurology referral
- Level 2: Application of the creatine kinase fork, the brain and eye assessment, and the gene panel to a specific diagnosis, and the initiation of respiratory and nutritional support
- Level 3: Coordination of the multidisciplinary care of a child with a congenital muscle disease across respiratory, orthopaedic, nutritional, and rehabilitation domains and the transition to adult care
- The division of congenital muscle disease into the dystrophic congenital muscular dystrophies and the structurally disordered congenital myopathies and the creatine kinase as the first fork
- The merosin-deficient LAMA2, collagen VI, dystroglycanopathy, LMNA, SEPN1, and titin forms of congenital muscular dystrophy and their brain, eye, and respiratory associations
- The central core, nemaline, and centronuclear congenital myopathies, the malignant hyperthermia risk in RYR1 disease, and the supportive multidisciplinary management
- Structured assessment of the floppy infant, including tone, power, reflexes, suck, swallow, respiratory effort, contractures, eyes, and cognitive development
- Recognition of the creatine kinase and brain and eye patterns that target the gene panel and the initiation of respiratory and nutritional support
- Communication of the diagnosis, the inheritance, the prognosis, and the multidisciplinary and family support plan
- The congenital muscular dystrophies and congenital myopathies as genetic causes of neonatal and infantile hypotonia and weakness in United States children
- The creatine kinase fork, the merosin-deficient and dystroglycanopathy patterns, and the multigene panel as the diagnostic standard
- The multidisciplinary management of respiratory failure, feeding difficulty, contractures, and scoliosis, and the malignant hyperthermia precautions in RYR1 disease
- Recognition of the floppy infant with reduced reflexes as a probable neuromuscular cause of hypotonia and the creatine kinase as the first diagnostic fork
- Distinguishing the congenital muscular dystrophies from the congenital myopathies and initiating the gene panel and the respiratory and nutritional support
- Multidisciplinary management of the respiratory, orthopaedic, nutritional, and rehabilitation needs and family counselling on inheritance and prognosis
- Canadian approach to the diagnosis of congenital muscle disease with the creatine kinase fork, brain and eye assessment, and next-generation sequencing panel
- The respiratory, nutritional, and orthopaedic management and the malignant hyperthermia and cardiac surveillance
- Coordination of multidisciplinary care, family counselling on inheritance and prenatal diagnosis, and transition to adult neuromuscular services
Overview & Definition
A baby born floppy, with a weak cry and a poor suck and limbs that slip through the hands, presents one of the defining diagnostic challenges of paediatric neurology, and congenital muscle disease is the explanation a clinician must not miss. Congenital myopathies and congenital muscular dystrophies are a group of inherited disorders of the structural and contractile proteins of skeletal muscle that present from birth or early infancy with hypotonia, weakness, and reduced or absent tendon reflexes, and they share a bedside picture that the paediatrician recognises as the floppy infant of neuromuscular origin. They are genetically diverse but clinically unified, and the task at the bedside is to separate the child whose creatine kinase is high and whose brain and eyes are involved from the child whose creatine kinase is normal and whose problem is confined to the muscle fibre. [1][5]
The single distinction that organises the whole field is the one between the muscular dystrophies and the myopathies, and it rests on what the muscle looks like under the microscope. In a congenital muscular dystrophy the muscle is dystrophic, meaning it shows active degeneration and regeneration with fibrosis and fatty replacement, because the protein that anchors the fibre to its surrounding basement membrane is defective and the fibre tears with every contraction. In a congenital myopathy the muscle is structurally disordered but not actively dying, and it shows a stable and characteristic abnormality such as central cores, nemaline rods, or centrally placed nuclei, because the proteins that build and organise the contractile apparatus are faulty. This distinction predicts the creatine kinase, the prognosis, and the genes, and it is the first fork in the diagnostic road. [1][4]
Why these diseases matter above all is that they can stop a child breathing even while the child is still walking, and they can hide a treatable or lethal complication such as malignant hyperthermia or cardiac arrhythmia behind a stable-looking weakness. The disease-modifying landscape is shifting, with emerging antisense and gene therapies for several forms, but the backbone of care remains the multidisciplinary management of respiratory failure, feeding difficulty, contractures, scoliosis, and rehabilitation. The paediatrician who recognises the floppy infant, sends the creatine kinase, and refers early to a neuromuscular service is the one who changes the trajectory. [2][3]
References11ShowHide
- [1]Bönnemann CG, Wang CH, Quijano-Roy S, et al Diagnostic approach to the congenital muscular dystrophies. Neuromuscul Disord, 2014.PMID 24581957
- [2]Wang CH, Bonnemann CG, Rutkowski A, et al Consensus statement on standard of care for congenital muscular dystrophies. J Child Neurol, 2010.PMID 21078917
- [3]Wang CH, Dowling JJ, North K, et al Consensus statement on standard of care for congenital myopathies. J Child Neurol, 2012.PMID 22431881
- [4]Nance JR, Dowling JJ, Gibbs EM, et al Congenital myopathies: an update. Curr Neurol Neurosci Rep, 2012.PMID 22392505
- [5]Muntoni F, Voit T The congenital muscular dystrophies in 2004: a century of exciting progress. Neuromuscul Disord, 2004.PMID 15351421
- [6]Coppens S, Deconinck N, Sullivan P, et al Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum. Ann Neurol, 2025.PMID 39853809
- [7]Ben Yaou R, Yun P, Dabaj I, et al International retrospective natural history study of LMNA-related congenital muscular dystrophy. Brain Commun, 2021.PMID 34240052
- [8]Angelin A, Tiepolo T, Sabatelli P, et al Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins. Proc Natl Acad Sci U S A, 2007.PMID 17215366
- [9]Mercuri E, Topaloglu H, Brockington M, et al Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations. Arch Neurol, 2006.PMID 16476814
- [10]Magri F, Brusa R, Bello L, et al Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis. Acta Myol, 2020.PMID 32904964
- [11]Amburgey K, Bailey A, Hwang JH, et al Genotype-phenotype correlations in recessive RYR1-related myopathies. Orphanet J Rare Dis, 2013.PMID 23919265