Myotonic dystrophy

Overview

•Most common adult-onset muscular dystrophy - prevalence ~1 in 8,000

•Autosomal dominant - DM1 (CTG repeat expansion in DMPK gene, chromosome 19q13) and DM2 (CCTG repeat expansion in CNBP gene)

•Anticipation - repeat expands with successive generations; earlier onset and more severe disease in offspring; most striking with maternal transmission (congenital DM1)

•Toxic RNA foci sequester MBNL1 splicing protein → aberrant splicing of multiple downstream targets → multisystem disease

Presentation

•Myotonia - delayed muscle relaxation; grip myotonia (cannot release handshake) and percussion myotonia (sustained dimple on thenar eminence)

•Distal muscle weakness - foot drop and wrist drop (distinguishes DM1 from most dystrophies which cause proximal weakness)

•Facial features - long thin face, bilateral ptosis, temporalis/masseter wasting, dysarthria, frontal baldness (even in females)

•Cataracts - posterior subcapsular (Christmas-tree); may precede neuromuscular symptoms

•Cardiac - conduction defects (first-degree block, bundle branch block, complete heart block), atrial/ventricular arrhythmias, sudden cardiac death

•Respiratory - type 2 respiratory failure, aspiration pneumonia, sleep apnoea

•Endocrine - insulin resistance (→ type 2 DM), testicular atrophy/hypogonadism, hypothyroidism

•Other - hypersomnia, cognitive/behavioural features, dysphagia, constipation

•Congenital DM1 - almost exclusively maternal transmission; severe neonatal hypotonia, respiratory failure, feeding difficulties, talipes; myotonia absent at birth (develops later); significant intellectual disability in survivors

🎯

DM1 causes distal weakness first - the opposite of almost every other muscular dystrophy. Frontal baldness even in females is a classic exam recognition feature.

Investigations

🏆 Gold standard

•Genetic testing - CTG repeat sizing in DMPK gene; definitive diagnosis, guides prognosis and family counselling

•EMG - myotonic discharges: high-frequency waxing-and-waning discharges; classic 'dive-bomber' sound

•CK - mildly elevated or normal (not a sensitive marker; contrast with DMD where dramatically raised)

•ECG - first-line cardiac assessment; PR prolongation, QRS widening, complete heart block

•Slit-lamp examination - detects posterior subcapsular cataracts before visible on direct ophthalmoscopy

•Pulmonary function tests - FVC supine detects diaphragmatic weakness; 24-hour Holter and echo for cardiac monitoring

Management

•No disease-modifying treatment - management is multidisciplinary and symptom-directed

•Myotonia - first-line: mexiletine (sodium channel blocker) 150 mg twice daily, titrate to effect; ECG monitoring required before and during treatment (pro-arrhythmic risk)

•Myotonia - second-line: lamotrigine or carbamazepine if mexiletine not tolerated

•Cardiac: Annual ECG surveillance; permanent pacemaker for symptomatic or high-degree heart block (PR >240 ms or QRS >120 ms warrants cardiology review); ICD for significant ventricular arrhythmia

•Respiratory: Annual PFTs; NIV/BiPAP for nocturnal hypoventilation or daytime hypercapnia; SALT assessment for dysphagia

•Ocular: Regular ophthalmology review; surgical cataract extraction when vision impaired

•Endocrine: Annual fasting glucose/HbA1c, TFTs, testosterone in symptomatic males

•Genetic counselling for all patients and at-risk family members; prenatal diagnosis and pre-implantation genetic testing available

🚨

Anaesthetic risk: volatile agents and suxamethonium can trigger generalised myotonia/myotonic crisis. Patients are exquisitely sensitive to opioids and benzodiazepines - standard doses can cause life-threatening respiratory failure. Regional anaesthesia preferred; inform anaesthetic team and ITU pre-operatively.

Complications and prognosis

•Leading causes of death - sudden cardiac death (complete heart block/VT) and respiratory failure

•Median age of death in classical DM1 - fifth to sixth decade

•Increased cancer risk - thyroid, colon, endometrial, and brain tumours

•Obstetric complications - polyhydramnios, preterm labour, uterine atony, postpartum haemorrhage

•Congenital DM1 carries worst prognosis; DM2 generally better prognosis than DM1