Muscular Dystrophies, Myotonic Dystrophy & Periodic Paralysis
The gait, the grip, and the potassium each point to a different muscle disease
Dystrophinopathies: Duchenne and Becker
Genetics. Both are X-linked recessive mutations of DMD (Xp21), the largest human gene, so about one-third of cases arise de novo. Dystrophin tethers actin to the dystroglycan complex and extracellular matrix; without it the sarcolemma tears with each contraction, causing myonecrosis and fibrofatty replacement. Duchenne affects about 1 in 3,500–5,000 boys.
Reading-frame rule. A frameshift deletion creates a premature stop codon and no dystrophin (Duchenne); an in-frame deletion yields a shorter, partly functional protein (Becker). Severity follows the frame, not the deletion size, and exon-skipping antisense drugs aim to turn a Duchenne transcript into a Becker-like one.
Duchenne presentation. Boys aged 2–5 walk late, toe-walk, fall often, and struggle on stairs. Pelvic-girdle weakness causes a waddling gait, lumbar hyperlordosis, and Gowers sign (pushing on the thighs to stand), which any proximal weakness can produce. Calves are enlarged but weak (pseudohypertrophy). About one-third have nonprogressive learning or cognitive impairment, and untreated boys stop walking by about 12.
Diagnosis. CK is 10–100 times normal (often above 10,000 U/L) from infancy; AST and ALT also leak from muscle, so check a CK before any liver work-up for unexplained "transaminitis." Next comes DMD deletion/duplication testing (MLPA or microarray), then sequencing if negative. Biopsy showing absent dystrophin is reserved for nondiagnostic genetics, and EMG adds little.
Management. Daily prednisone or deflazacort from about age 4–6 prolongs walking by roughly 2–3 years and delays scoliosis and cardiorespiratory decline. Dilated cardiomyopathy is nearly universal, so obtain regular echocardiography or cardiac MRI and start an ACE inhibitor (or ARB) by age 10. Scoliosis accelerates after wheelchair dependence (spinal fusion), and restrictive respiratory failure needs cough assistance and nocturnal noninvasive ventilation. Death usually comes in the 20s–30s; female carriers can also develop cardiomyopathy.
Avoid succinylcholine and volatile anesthetics in dystrophinopathies: anesthesia-induced rhabdomyolysis can cause hyperkalemic cardiac arrest.
Becker. Onset usually at 5 to 15 years, sometimes in adulthood; cramps and exercise-induced myoglobinuria, walking past 16, and survival into middle age. Cardiomyopathy can outpace the weakness and is the usual cause of death.
Myotonic dystrophy type 1
Genetics. DM1, the most common adult-onset dystrophy, is an autosomal dominant CTG expansion in the 3′ untranslated region of DMPK (chromosome 19). The toxic CUG RNA sequesters the splicing regulator MBNL1, missplicing the muscle chloride channel (myotonia) and the insulin receptor (insulin resistance). Repeats lengthen across generations (anticipation), and large expansions from an affected mother cause congenital DM1: polyhydramnios, neonatal hypotonia, respiratory failure, and clubfoot.
Phenotype. Myotonia shows as slow release of a handshake and percussion myotonia of the thenar eminence. Weakness is distal, facial, and in the neck flexors, unusual because most dystrophies and myositis are proximal. Ptosis, temporal and masseter wasting ("hatchet face"), frontal balding, early posterior subcapsular cataracts, testicular atrophy and infertility, insulin resistance, hypersomnolence, dysphagia, and GI dysmotility complete the picture. EMG shows waxing-and-waning "dive-bomber" discharges, CK is normal or mildly raised, and repeat sizing confirms.
Heart. Conduction-system fibrosis causes PR and QRS prolongation, AV block, and atrial or ventricular arrhythmias, a major cause of sudden death. Obtain an ECG at diagnosis and yearly, a Holter or electrophysiology study if abnormal, and a pacemaker or ICD as indicated. Mexiletine can ease disabling myotonia after ECG review. DM2 (CCTG repeat in CNBP) is milder and proximal and has no congenital form.
Sedatives, opioids, and anesthetics cause prolonged hypoventilation in DM1, and succinylcholine can provoke myotonic spasm; minimize them and extend postoperative monitoring.
Facioscapulohumeral dystrophy
FSHD. Autosomal dominant contraction of the D4Z4 repeat on 4q35 allows toxic DUX4 expression. Onset in the teens–20s brings facial weakness (cannot whistle, sip through a straw, or bury the eyelashes), scapular winging, and biceps and triceps wasting with a spared deltoid; the facial weakness separates it from an isolated long thoracic nerve palsy. Weakness is strikingly asymmetric, with foot drop and lower-abdominal weakness (Beevor sign: the umbilicus rises on neck flexion). CK is normal to mildly raised and the heart is usually spared.
Periodic paralysis
Primary channelopathies. Autosomal dominant ion-channel mutations cause attacks of flaccid limb weakness with normal strength between them. Reflexes fall during attacks, but sensation, consciousness, and breathing are usually spared.
| Feature | Hypokalemic | Hyperkalemic | Thyrotoxic |
|---|---|---|---|
| Cause | CACNA1S or SCN4A; teens | SCN4A; early childhood | Graves disease; young Asian or Hispanic men |
| Attacks | Hours to a day; after carb-rich meals or rest after exercise | Brief, frequent; after fasting, potassium intake, rest after exercise; myotonia | After carbohydrate loads or rest after exercise |
| K in attack | Low | High or normal | Low (shift; urine K low) |
| Acute treatment | Oral KCl; avoid IV dextrose | Carbohydrate, inhaled albuterol | Propranolol plus small KCl doses |
| Prevention | Acetazolamide or dichlorphenamide | Thiazide or a carbonic anhydrase inhibitor (dichlorphenamide, FDA approved for both forms; acetazolamide) | Restore euthyroidism |
Thyrotoxic periodic paralysis. Thyroid hormone, amplified by insulin after a carbohydrate load and by catecholamines, upregulates Na⁺/K⁺-ATPase and drives potassium into muscle. Thyrotoxic signs are often subtle. Low urine potassium signals a shift, whereas high urine potassium points to renal wasting (diuretics, hyperaldosteronism). Propranolol, a nonselective β-blocker, reverses the shift within hours; methimazole is definitive but takes weeks, and attacks stop once the patient is euthyroid.
Total-body potassium is normal in thyrotoxic periodic paralysis: give small KCl doses and recheck often, because aggressive repletion causes rebound hyperkalemia.
Sorting the weak patient: CK and TSH
Episodic weakness with a normal CK between attacks suggests periodic paralysis, so measure potassium during the attack and TSH. A high CK points to a dystrophy or an acquired myopathy:
- Inflammatory: progressive symmetric proximal weakness, markedly high CK, ± rash and myositis antibodies.
- Statin: myalgia or weakness with high CK; stop the drug, and suspect anti-HMGCR necrotizing myopathy if weakness persists after withdrawal.
- Hypothyroid: cramps, slow-relaxing reflexes, raised CK, and high TSH; resolves with levothyroxine.
- Hyperthyroid or steroid: proximal weakness with a normal CK.
Check TSH in every new myopathy: hypothyroidism raises CK itself and increases the risk of statin myotoxicity.