Congenital Myotonic Dystrophy

Congenital myotonic dystrophy is the severe neonatal form of myotonic dystrophy type 1, caused by a large CTG trinucleotide repeat expansion (usually over 1000 repeats) in the DMPK gene on chromosome 19. It presents with profound neonatal hypotonia, respiratory failure and feeding difficulty.

Inheritance is autosomal dominant, and the congenital form is almost always inherited from an affected mother, often unrecognised, because of maternal transmission of large expansions. The incidence of myotonic dystrophy type 1 is about 1 in 8000, and the congenital form is a small proportion.

Neonatal mortality is substantial (about 15 to 40%), mostly from respiratory failure. Survivors have motor and intellectual disability, and develop adult features later in childhood and adolescence.

Pathophysiology.

Expanded CUG repeat RNA accumulates in the nucleus and sequesters splicing proteins, causing abnormal splicing of many genes (including the chloride channel and insulin receptor). The result is muscle weakness, myotonia, and multisystem disease.

Repeat expansion increases across generations (anticipation), particularly when transmitted by the mother.

• Antenatal: polyhydramnios, reduced foetal movements, talipes and prematurity.
• Neonatal: profound hypotonia and weakness, respiratory failure needing ventilation, facial diplegia (tented upper lip, open mouth), absent suck and swallow, and joint contractures.
• Gastrointestinal: aspiration, reflux and constipation. Clinical myotonia is usually absent in the newborn period.
• Later: delayed motor and speech development, intellectual disability, learning and behavioural problems, myotonia from late childhood, cardiac conduction defects and cataracts.

Red flags.

• Respiratory failure, apnoea or inability to feed in a hypotonic newborn.
• Cardiac arrhythmia or conduction block.
• Maternal weakness, myotonia (difficulty releasing a grip), cataracts or a family history of muscle disease.

• Molecular testing of the DMPK CTG repeat (Southern blot or triplet repeat primed PCR), which is diagnostic. Congenital disease usually has over 1000 repeats.
• Examine the mother and relatives for myotonia, facial weakness and cataract. Electromyography of the mother shows myotonic discharges. Test the mother and offer cascade testing.
• Chest X-ray, creatine kinase (normal or mildly raised), echocardiography and ECG, and cranial ultrasound or MRI (ventriculomegaly is common).
• Exclude other causes of neonatal hypotonia: spinal muscular atrophy, Prader-Willi syndrome, congenital myopathies, hypoxic ischaemic encephalopathy, sepsis and metabolic disease.

Differential diagnosis. Spinal muscular atrophy, Prader-Willi syndrome, congenital myopathies, congenital muscular dystrophies, congenital myasthenic syndromes, botulism, hypoxic ischaemic encephalopathy and sepsis.

• Neonatal resuscitation and ventilation, with respiratory support (CPAP or ventilation) as needed. Many infants who survive the first weeks improve and wean from ventilation. Provide a clear discussion with the family about prognosis in those with prolonged ventilation.
• Feeding: nasogastric or gastrostomy feeding, reflux treatment, and swallowing assessment.
• Orthopaedic management of talipes and contractures with serial casting and physiotherapy.
• Cardiac: ECG and echocardiography at diagnosis, and regular follow up for conduction defects and arrhythmia, with pacemaker or defibrillator when indicated.
• Developmental support, speech therapy, and educational support. Treat constipation and monitor vision for cataracts.
• Anaesthesia: high risk of respiratory complications. Avoid or use minimal doses of sedatives, opioids and depolarising muscle relaxants (suxamethonium), and monitor closely after anaesthesia.
• Genetic counselling for the family. Offer prenatal and preimplantation testing in future pregnancies.

Monitoring. Respiratory function, cardiac rhythm, swallowing, growth and development throughout childhood.

Referral and escalation. Refer to neonatal intensive care, neuromuscular, cardiology and genetics teams at diagnosis.

Special groups. Mothers with myotonic dystrophy carry obstetric risks (preterm labour, anaesthetic complications) and need specialist obstetric and anaesthetic planning.