Myotonic dystrophy

1. High-Yield Summary

Myotonic dystrophy represents the most prevalent adult-onset muscular dystrophy, inherited in an autosomal dominant pattern with prominent multisystem involvement. Orthopaedic surgeons frequently encounter patients with myotonic dystrophy during the evaluation of bilateral foot drop, recurrent ankle inversion injuries, neuromuscular scoliosis, joint contractures, or during emergency trauma consultations.

• Genetic Architecture: Type 1 (DM1, Steinert disease) is caused by an unstable CTG trinucleotide repeat expansion in the 3′ untranslated region of the DMPK gene on chromosome 19q13.3; Type 2 (DM2, PROMM) involves a CCTG tetranucleotide repeat in intron 1 of the CNBP gene on chromosome 3q21.3.
• Motor Weakness Distribution: Classical DM1 presents with distal-predominant weakness (tibialis anterior, intrinsic hand muscles, deep finger flexors) and facial/cervical wasting (“hatchet facies”); DM2 demonstrates proximal-predominant pelvic and shoulder girdle weakness with prominent exercise-induced myalgias.
• Clinical Hallmark: Myotonia, characterized by impaired relaxation of skeletal muscle after voluntary contraction or direct mechanical percussion (grip and thenar percussion myotonia), mediated by aberrant alternative splicing of the muscle chloride channel 1 (CLCN1).
• Critical Anesthetic Contraindication: Depolarizing neuromuscular blocking agents (succinylcholine) are absolutely contraindicated due to the risk of triggering severe, intractable generalized myotonic contractures, masseter spasm, and life-threatening hyperkalemia. Anticholinesterase reversal agents (neostigmine) can paradoxically exacerbate myotonia; sugammadex is the reversal agent of choice.
• Surgical Principle: Orthopaedic reconstruction prioritizes plantigrade foot positioning via custom ankle-foot orthoses (AFOs) or posterior tibial tendon transfers to midfoot dorsum, judicious management of neuromuscular spinal deformity, and mandatory perioperative cardiac rhythm and pulmonary surveillance.

2. Anatomy

Understanding the anatomical distribution of myotonic dystrophy requires differentiating neuromuscular target patterns, surgical corridors for corrective tendon transfers, and regional neurovascular danger zones.

Musculoskeletal Target Patterns

The musculoskeletal anatomy affected by myotonic dystrophy exhibits distinct topographic predilections depending on the genetic subtype:

• Lower Extremity (DM1): Primary weakness targets the anterior compartment of the leg, specifically the tibialis anterior, extensor hallucis longus, and extensor digitorum longus. Progressive loss of ankle dorsiflexion leads to an unresisted plantarflexion vector by the gastrocnemius-soleus complex, culminating in dynamic and eventual structural equinus or equinovarus deformities. Distal intrinsic foot musculature atrophies, compromising the medial longitudinal arch.
• Upper Extremity (DM1): Distal forearm and hand intrinsics suffer early selective atrophy. The thenar eminence (abductor pollicis brevis, opponens pollicis) and deep finger flexors (flexor digitorum profundus) display significant wasting, causing impaired pinch and grasp power alongside classic grip myotonia.
• Cervical and Craniofacial (DM1): Severe atrophy of the sternocleidomastoid muscles and anterior neck flexors produces marked cervical weakness (“swan-neck” deformity). Facial muscle wasting affects the temporalis, masseter, and orbicularis oculi, creating ptosis, temporal hollows, and a drooping jaw.
• Proximal Girdles (DM2): In contrast to DM1, DM2 primarily impairs the hip flexors (iliopsoas), hip extensors (gluteus maximus), hip abductors (gluteus medius), and quadriceps femoris, producing a Trendelenburg gait and difficulty rising from a chair without upper extremity assistance.

Neurovascular Danger Zones & Operative Corridors

When performing tendon transfers or soft tissue releases to correct lower extremity foot drop in DM1 patients, surgeons navigate vulnerable anatomic danger zones:

• Deep Peroneal Nerve Corridor: During posterior tibial tendon transfer routed through the interosseous membrane into the anterior compartment, the anterior tibial artery, venae comitantes, and deep peroneal nerve lie directly on the anterior surface of the interosseous membrane. The window created through the interosseous membrane must measure at least 4 to 5 cm in longitudinal length and be placed immediately adjacent to the lateral tibial border to prevent neurovascular compression, graft entrapment, or vascular compromise.
• Tibial Nerve and Posterior Tibial Artery: In the deep posterior compartment of the lower leg, the tibialis posterior muscle belly is mobilized off the posterior tibia and interosseous membrane. The tibial nerve and posterior tibial neurovascular bundle run along the posterior surface of the tibialis posterior and flexor digitorum longus. Dissection must remain strictly subperiosteal along the lateral tibial crest to preserve vascularity to the posterior tibial nerve trunk.
• Superficial Peroneal Nerve: During lateral midfoot exposure for tendon anchoring into the lateral cuneiform or cuboid, the medial and intermediate dorsal cutaneous branches of the superficial peroneal nerve traverse the subcutaneous tissue directly overlying the target dorsal tarsal bones and must be carefully identified and protected.

3. Pathogenesis

Myotonic dystrophy represents the prototypical human disorder of RNA gain-of-function toxicity, where microsatellite repeat expansions disrupt normal alternative splicing across diverse organ systems.

Molecular Genetics & Unstable Repeat Expansions

In DM1, an unstable cytosine-thymine-guanine (CTG) trinucleotide repeat expansion occurs within the 3′ untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) gene located on chromosome 19q13.3. Unaffected individuals possess between 5 and 34 CTG repeats. Individuals with 35 to 49 repeats carry premutations. Clinically affected patients exhibit between 50 and several thousand CTG repeats. The unstable expansion exhibits marked somatic and germline instability, driving genetic anticipation (earlier age of onset and greater phenotypic severity in successive generations), particularly through maternal transmission in congenital presentations.

In DM2, an unstable cytosine-cytosine-thymine-guanine (CCTG) tetranucleotide repeat expansion is located within intron 1 of the cellular nucleic acid-binding protein (CNBP, formerly ZNF9) gene on chromosome 3q21.3. Normal alleles contain fewer than 30 CCTG repeats, whereas pathogenic alleles range from 75 to over 11,000 repeats. DM2 does not exhibit significant anticipation, lacks a congenital subtype, and demonstrates milder clinical variability.

Toxic RNA Gain-of-Function & Spliceopathy

The pathogenic cascade does not stem primarily from protein deficiency, but from mutant nuclear RNA accumulation:

• Nuclear Foci Formation: Mutant transcripts containing expanded CUG (DM1) or CCUG (DM2) repeats fold into hairpin-like double-stranded structures that resist normal nuclear export and form ribonuclear aggregates or “nuclear foci.”
• Sequestration of Splicing Factors: The expanded repeat RNA exhibits an extraordinarily high affinity for Muscleblind-like (MBNL) family proteins (principally MBNL1 and MBNL2), trapping them within nuclear foci. Simultaneously, protein kinase C activation stabilizes and upregulates CUGBP and Elav-like family member 1 (CELF1).
• Downstream Mis-Splicing: The antagonistic loss of MBNL1 and hyperactivation of CELF1 causes fetal splicing patterns to persist into adult differentiated tissues:
• CLCN1 (Chloride Channel 1): Inclusion of fetal exon 7a introduces a premature termination codon, targeting the mRNA for nonsense-mediated decay. The resulting reduction in sarcolemmal resting chloride conductance causes membrane hyperexcitability and delayed muscle relaxation (myotonia).
• BIN1 (Bridging Integrator 1): Aberrant inclusion of exon 11 disrupts transverse tubule structural biogenesis, leading to progressive muscle weakness and myofibrillar degeneration.
• RYR1 & CACNA1S: Calcium release and voltage-gated channel mis-splicing impair excitation-contraction coupling.
• SCN5A (Cardiac Sodium Channel): Aberrant inclusion of fetal exon 6B predisposes patients to life-threatening cardiac conduction delays, atrioventricular block, and ventricular arrhythmias.
• INSR (Insulin Receptor): Exclusion of exon 11 results in the low-affinity fetal isoform, producing systemic insulin resistance and diabetes mellitus.

4. Natural History

Myotonic dystrophy is characterized by progressive muscular degeneration coupled with multi-organ systemic deterioration, necessitating continuous interdisciplinary surveillance.

Epidemiology

Meta-analyses establish a global pooled prevalence of myotonic dystrophy of approximately 9.27 per 100,000 population. DM1 represents the vast majority of identified cases with a prevalence of 8.26 per 100,000, whereas DM2 exhibits a diagnosed prevalence of 0.99 per 100,000. However, regional founder effects exist; in the Saguenay-Lac-Saint-Jean region of Quebec, Canada, the prevalence of DM1 reaches 1 in 500 live births. Recent population genetic screening studies indicate that the true genetic prevalence of pre-symptomatic or undiagnosed repeat expansions may be as high as 1 in 2,100 individuals, demonstrating substantial diagnostic underascertainment in clinical practice.

Disease Progression & Prognosis

The clinical course of DM1 correlates closely with CTG repeat length and the age at disease onset:

• Congenital DM1: Manifests in neonates with severe polyhydramnios, generalized hypotonia, bilateral talipes equinovarus (clubfoot), and acute respiratory distress. Neonatal mortality approaches 15% to 25% due to respiratory failure. Surviving infants develop significant cognitive delay, speech impairment, and progressive facial and distal weakness.
• Classical Adult-Onset DM1: Typically begins in the second to fourth decades of life with distal hand stiffness, grip myotonia, and subtle ankle dorsiflexor weakness. Weakness steadily advances at a rate of 1% to 3% loss of muscle strength per year. Mobility aids (canes, orthoses, wheelchairs) become necessary within 15 to 20 years of onset.
• Mortality: Median life expectancy in classical DM1 is reduced to approximately 53 to 60 years. The leading causes of mortality are acute respiratory failure or aspiration pneumonia (50% to 60% of deaths) and sudden cardiac death secondary to fatal arrhythmias or complete heart block (20% to 30% of deaths).
• DM2 Course: Disease progression in DM2 is substantially more indolent. Life expectancy is generally near normal, and severe respiratory compromise or wheelchair dependency occurs infrequently.

5. Clinical Presentation

Evaluation requires a systematic approach to capture both musculoskeletal pathology and subtle multisystem indicators of the underlying myopathy.

History

Clinicians must actively inquire about characteristic symptoms that patients often underreport or dismiss as constitutional clumsiness:

• Locomotor & Balance Symptoms: Frequent tripping over rugs or uneven ground, catching toes during swing phase (foot drop), recurrent ankle sprains, difficulty ascending stairs, or sudden unexplained falls.
• Myotonia Symptoms: Difficulty releasing doorknobs, releasing a handshake, opening jars, or unclenching fingers in cold weather. Patients often note that rapid, repetitive hand movements temporarily improve stiffness (the “warm-up phenomenon”).
• Systemic & Multisystem Review: Early-onset iridescent posterior subcapsular cataracts (diagnosed before age 50), excessive daytime somnolence, fatigue out of proportion to exertion, dysphagia, choking episodes, chronic diarrhea or constipation, palpitations, syncope or presyncope, and family history of sudden cardiac death or early pacemakers.

Physical Examination

Examination should incorporate targeted provocative maneuvers, motor grading, and gait analysis:

• Action / Grip Myotonia: The patient is asked to make a tight fist for 5 seconds and then open the hand as rapidly as possible. A positive finding is marked delay (3 to 10 seconds) in finger extension with a gradual, tonic unfolding of the digits (Sensitivity 92%, Specificity 98% in DM1).
• Percussion Myotonia: A reflex hammer is used to firmly tap the mid-portion of the thenar eminence. A positive finding is rapid abduction and opposition of the thumb that remains sustained in contracture for several seconds before slow relaxation (Sensitivity 88%, Specificity 96%). Percussion over the wrist extensors or lateral tongue border similarly elicits sustained focal contractions.
• Craniofacial Inspection: Bilateral symmetric ptosis, temporal hollows from temporalis muscle atrophy, hollowed cheeks from masseter wasting, thin lips with an inverted V-shaped upper lip (“tent-shaped mouth”), and frontal balding in males.
• Manual Muscle Testing: Systematic evaluation of the Medical Research Council (MRC) grade reveals profound weakness of the tibialis anterior (often MRC grade 2 or 3) with relatively preserved gastrocnemius-soleus strength (MRC grade 4 or 5) in DM1. Deep neck flexors demonstrate early failure on resisted cervical flexion. In DM2, hip abductors and quadriceps exhibit symmetric weakness.
• Gait Analysis: High-stepping “steppage gait” with bilateral foot slap during loading response. Compensatory pelvic hiking or circumduction occurs to clear dropped toes during swing phase. Gowers sign may be present in advanced cases or DM2.

6. Imaging and Diagnostic Studies

Diagnostic confirmation relies on targeted molecular genetics, supported by electrophysiologic and baseline multidisciplinary cardiopulmonary staging.

Molecular Genetic Testing (Gold Standard)

Polymerase chain reaction (PCR) and repeat-primed PCR (RP-PCR) of peripheral blood leukocyte DNA confirm the diagnosis. In DM1, RP-PCR detects expanded CTG alleles up to several hundred repeats; large expansions (>1,000 repeats) are characterized using Southern blot analysis to determine exact repeat sizing. In DM2, RP-PCR and Southern blotting targeting the CNBP intron 1 CCTG expansion are diagnostic. Muscle biopsy is rarely indicated today, though historical histopathology reveals marked variation in fiber size, abundant central nuclei in up to 50% of fibers, selective type 1 fiber atrophy, and sarcoplasmic masses.

Electromyography (EMG)

Needle electromyography demonstrates characteristic myotonic discharges. Upon needle insertion or voluntary contraction, high-frequency repetitive electrical discharges (10 to 100 Hz) spontaneously fire and progressively wax and wane in both amplitude and frequency. Audio playback through the EMG amplifier produces the distinctive pathognomonic acoustic effect often compared to a “dive-bomber” or revving motorcycle engine. Associated myopathic motor unit action potentials (short duration, small amplitude, polyphasic units) confirm primary muscle pathology.

Cardiopulmonary & Preoperative Investigations

Prior to any planned orthopaedic intervention, comprehensive cardiopulmonary staging is mandatory:

• 12-Lead Electrocardiogram (ECG): Screened for baseline conduction defects including PR interval prolongation (>200 ms), QRS widening (>120 ms), left anterior fascicular block, or bundle branch blocks. Conduction abnormalities occur in over 50% of patients and warrant urgent electrophysiology consultation for prophylactic pacemaker or implantable cardioverter-defibrillator (ICD) consideration.
• Echocardiography: Assessment of left ventricular systolic function, myocardial strain, and chamber dimensions to detect subclinical dilated cardiomyopathy.
• Pulmonary Function Tests (PFTs): Spirometry measuring Forced Vital Capacity (FVC) in both the seated upright and supine positions. A decrease in supine FVC greater than 20% to 25% signifies severe diaphragmatic weakness and heralds high risk for postoperative respiratory arrest. Polysomnography assesses nocturnal hypoventilation and central versus obstructive sleep apnea.

Musculoskeletal Imaging

Weight-bearing radiographs of the bilateral feet and ankles evaluate equinus contracture, talonavicular subluxation, calcaneal pitch, and secondary degenerative joint disease. Full-length standing spine radiographs (PA and lateral) assess coronal Cobb angle, sagittal balance, and pelvic obliquity in patients with neuromuscular scoliosis. Magnetic resonance imaging (MRI) of lower extremity musculature reveals selective fatty infiltration and atrophy of the tibialis anterior, medial gastrocnemius, and soleus, with relative sparing of the tibialis posterior, which supports its utility as a transfer donor.

7. Classification

Myotonic dystrophy is classified according to genetic repeat size, age of clinical onset, and phenotypic severity, which directly guides clinical management and surveillance intensity.

8. Treatment

Management requires an integrated multidisciplinary paradigm combining conservative bracing, medical symptom control, and highly selective surgical stabilization when functional mobility is compromised.

Medical / Nonoperative Management

Nonoperative care forms the primary foundation of musculoskeletal maintenance:

• Orthotic Bracing: Custom-molded lightweight carbon-fiber or articulated polypropylene Ankle-Foot Orthoses (AFOs) with dorsiflexion assist are the gold standard for managing foot drop. By eliminating toe drag in the swing phase, AFOs prevent tripping, normalize energy expenditure during gait, and protect the unstable ankle from recurrent inversion injuries. Rigid night splints are employed to counter nocturnal gastrocnemius tightness.
• Physical Therapy & Exercise: Supervised moderate-intensity aerobic exercise combined with low-resistance functional strength training improves functional capacity and reduces chronic fatigue. High-intensity eccentric loading is avoided to minimize muscle damage. Passive stretching protocols prevent Achilles tendon contracture.
• Pharmacotherapy for Myotonia: Mexiletine (sodium channel blocker, 150 to 200 mg orally two to three times daily) is the first-line medication for disabling myotonia. Because mexiletine possesses class IB antiarrhythmic properties, a baseline ECG and serial cardiology evaluations are mandatory to ensure the PR and QTc intervals remain within safe thresholds. Alternative agents include carbamazepine and lamotrigine.
• Respiratory Management: Nocturnal non-invasive positive pressure ventilation (BiPAP) is initiated upon evidence of sleep-disordered breathing, daytime hypercapnia, or significant reduction in supine FVC.

Operative Management

Surgical intervention targets correction of fixed skeletal deformities, dynamic tendon balancing for persistent foot drop, and spinal realignment:

• Goals of Surgery: Provide a stable, pain-free, plantigrade foot that accommodates standard footwear; prevent recurrent fall-related trauma; and preserve independent ambulatory function while minimizing perioperative cardiopulmonary morbidity.
• Tendon Transfer for Foot Drop (Posterior Tibial Tendon Transfer): In mobile feet where the tibialis anterior is paralyzed (MRC grade 0 to 2) but the posterior tibialis retains strong voluntary power (MRC grade 4 or 5), a posterior tibial tendon transfer (PTTT) to the dorsum of the midfoot is performed. The tendon is harvested from its navicular insertion, routed through a wide window in the interosseous membrane into the anterior compartment, and anchored into the lateral cuneiform or cuboid using interference screw fixation or a cortical button. Concomitant percutaneous or open Achilles tendon lengthening (Z-lengthening) or gastrocnemius recession (Strayer procedure) is simultaneously performed to relieve fixed equinus.
• Arthrodesis for Fixed Deformities: When chronic muscle imbalance results in rigid, uncorrectable equinovarus or secondary subtalar and midtarsal arthrosis, tendon transfer alone will fail. Subtalar arthrodesis, triple arthrodesis (talonavicular, subtalar, and calcaneocuboid), or pantalar arthrodesis is required to achieve a durable, plantigrade foot.
• Congenital Clubfoot Correction: In neonatal congenital DM1, initial management utilizes serial Ponseti casting. However, clubfoot in this population is inherently rigid and neuromuscular; percutaneous Achilles tenotomy is almost universally required, and resistant deformities frequently necessitate extensive posteromedial soft-tissue release.
• Neuromuscular Scoliosis Stabilization: Progressive curves exceeding 50 degrees in juvenile or adolescent patients compromise sitting balance and further restrict already impaired pulmonary capacity. Posterior spinal instrumentation and fusion from T2 to the sacrum/pelvis are indicated. Intraoperative cell salvage, warm operating rooms, total intravenous anesthesia without depolarizing agents, and planned postoperative mechanical ventilatory weaning are mandatory.

Indications & Contraindications

Objective numerical and clinical parameters determine surgical candidacy:

• Surgical Indications:
  • Fixed ankle equinus contracture preventing neutral dorsiflexion (dorsiflexion with knee extended < 0 degrees) despite 6 months of dedicated bracing.
  • Severe dynamic foot drop refractory to orthotic fitting resulting in recurrent falls.
  • Rigid subtalar varus deformity with painful lateral border weight-bearing and recurrent skin breakdown.
  • Neuromuscular scoliosis with a progressive coronal Cobb angle > 50 degrees and loss of sitting balance.
• Contraindications:
  • Active, uncorrected high-grade cardiac conduction block (bifascicular block, Mobitz II second-degree AV block, complete heart block) without an in situ permanent pacemaker.
  • Severe uncompensated restrictive lung disease with awake hypercapnia (PaCO2 > 45 mm Hg) or supine FVC < 35% of predicted without established home non-invasive ventilatory support.
  • Absence of an intact motor donor: Attempting posterior tibial tendon transfer when the posterior tibialis muscle is atrophied or has an MRC grade < 4.
  • Complete loss of ambulatory capacity or non-functional bedbound status (relative contraindication for complex reconstruction).

9. Outcome

Surgical outcomes in myotonic dystrophy depend primarily on meticulous patient selection, realistic functional goals, and proactive prevention of systemic complications.

• Foot Drop Correction: Posterior tibial tendon transfer combined with Achilles lengthening provides successful restoration of active neutral dorsiflexion in 70% to 80% of carefully selected ambulatory DM1 patients. Patient-reported mobility scores, gait velocity, and foot posture indices show significant improvements, with a marked reduction in trip-and-fall episodes. Over long-term follow-up (5 to 10 years), gradual donor muscle attenuation may occur due to underlying disease progression, requiring secondary supportive bracing.
• Arthrodesis Survivorship: Triple and ankle arthrodesis achieve osseous union rates between 85% and 92%. Delayed union or pseudoarthrosis is increased compared to non-neuromuscular cohorts due to poor bone mineral density from reduced weight-bearing and nutritional factors. Rigid fixation using modern locking plates and intramedullary nails significantly enhances union rates.
• Spine Deformity Outcomes: Posterior spinal fusion effectively halts curve progression, restores coronal and sagittal spinal balance, and improves sitting comfort in wheelchair-dependent patients. However, major perioperative pulmonary complications occur in up to 30% of patients undergoing extensive spinal surgery.

10. Complications

Complications in myotonic dystrophy encompass both catastrophic systemic cardiopulmonary events and procedure-specific orthopaedic failures.

11. Pearls and Pitfalls

Expert clinical management requires navigating unique diagnostic subtleties and avoiding surgical traps:

• The Shivering Crisis Pearl: Shivering in the post-anesthesia care unit is one of the most potent triggers of generalized intractable myotonic contractures. Maintain aggressive active warming with forced-air warming blankets and warm intravenous fluids throughout the entire operative and recovery periods.
• The Neostigmine Trap Pitfall: Never administer acetylcholinesterase inhibitors (such as neostigmine) for neuromuscular blockade reversal. Increased acetylcholine at the neuromuscular junction can trigger catastrophic, refractory myotonic spasms. Always utilize rocuronium or vecuronium reversed with sugammadex, which encapsulates the relaxant directly without cholinergic stimulation.
• Tendon Route Dimension Pearl: When performing a posterior tibial tendon transfer through the interosseous membrane, create an excessively generous window (minimum 4 to 5 cm in length). A tight aperture causes scarring, tendon adherence, and loss of excursion, which is the most common cause of transfer failure.
• The “Silent Aspiration” Pitfall: Pharyngeal weakness and cricopharyngeal dysfunction are common even in mildly symptomatic DM1 patients. Routine postoperative oral intake must not be cleared until formal bedside swallowing evaluation confirms airway protection, preventing chemical aspiration pneumonitis.
• Tensioning Pearl for Foot Drop: When securing the transferred posterior tibial tendon into the lateral cuneiform, anchor the foot in 10 to 15 degrees of dorsiflexion and neutral inversion/eversion under maximal manual tension. Transferred neuromuscular units invariably stretch and lose 5 to 10 degrees of tension over the initial 6 postoperative months.

12. Controversy

Several major areas of debate continue to evolve regarding optimal musculoskeletal and surgical management in myotonic dystrophy:

• Dynamic Tendon Transfer vs. Lifelong Custom Bracing: Advocates of early posterior tibial tendon transfer argue that restoring active dorsiflexion frees the patient from cumbersome orthoses, improves proprioception, and eliminates trip-induced fractures. Conversely, skeptics emphasize that because myotonic dystrophy is a progressive disorder, the transferred posterior tibialis muscle will inevitably undergo dystrophic degeneration over a 5- to 10-year horizon, ultimately necessitating bracing anyway while exposing the patient to substantial perioperative anesthesia risks. Modern consensus favors surgery in motivated, active patients with isolated anterior compartment weakness and robust posterior compartment strength, coupled with rigorous pre-anesthetic optimization.
• Prophylactic Pacemaker Placement Before Elective Surgery: In patients with normal baseline resting ECGs or minor PR prolongation (200 to 220 ms) without documented high-grade block, the threshold for invasive electrophysiological studies (EPS) or prophylactic permanent pacemaker insertion prior to major elective orthopaedic surgery remains controversial. While European guidelines recommend proactive EPS for HV interval measurement (>70 ms triggering pacing), North American centers frequently rely on continuous telemetry monitoring unless symptoms of syncope or advanced fascicular block are present.
• Emerging Splice-Switching & Antisense Oligonucleotide Therapeutics: Preclinical and phase 1/2 clinical trials utilizing antisense oligonucleotides (ASOs) and small molecules designed to block CUG repeats and liberate sequestered MBNL1 have demonstrated reversal of spliceopathy and reduction of myotonia in animal models. The controversy centers on whether future systemic genetic therapies will reverse established muscle atrophy and fixed contractures, or whether early orthopaedic structural balancing will remain essential to preserve biomechanical alignment.

13. Evidence-Based Synthesis

Modern clinical decision-making is grounded in high-quality randomized controlled trials and prospective registry analyses, corroborated by seminal biomechanical and anatomical descriptions.

14. References

• Liao Q, Zhang Y, He J et al. Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis. Neuroepidemiology. 2022. doi:10.1159/000524734 [Level I: Systematic Review / Meta-Analysis]
• Leone E, Pandyan A, Rogers A et al. Effectiveness of conservative non-pharmacological interventions in people with muscular dystrophies: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2024. doi:10.1136/jnnp-2023-331988 [Level I: Systematic Review / Meta-Analysis]
• Turner C, Hilton-Jones D. The myotonic dystrophies: diagnosis and management. J Neurol Neurosurg Psychiatry. 2010. doi:10.1136/jnnp.2008.158261 [Level V: Expert Consensus & Clinical Practice Review]
• Thornton CA. Myotonic dystrophy. Neurol Clin. 2014. doi:10.1016/j.ncl.2014.04.011 [Level V: State-of-the-Art Comprehensive Review]
• Brook JD, McCurrach ME, Harley HG et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell. 1992. doi:10.1016/0092-8674(92)90154-5 [Level V: Seminal Molecular & Genetic Discovery]

15. Master Class Pro-Tip

When operating on a patient with myotonic dystrophy, remember that the most dangerous phase of the procedure is not the surgical dissection, but the emergence from anesthesia. Never allow the patient to become hypothermic, as postoperative shivering triggers a profound, sustained myotonic crisis that can prevent ventilation. Ensure that the surgical suite is maintained at a minimum of 22 degrees Celsius, administer actively warmed intravenous fluids, and position forced-air warming blankets over all unexposed body surfaces. Completely avoid depolarizing neuromuscular blockade with succinylcholine, and never use anticholinesterases for reversal. Plan extubation directly to non-invasive positive pressure ventilation (BiPAP), and mandate a minimum of 24 hours of continuous cardiac telemetry and pulse oximetry monitoring in a high-dependency unit, regardless of how minor the orthopaedic procedure may appear.

Master Class Surgical Pearl: Perioperative Neuromuscular Safety in Myotonic Dystrophy