Neurology & Medical Genetics & Internal Medicine
Muscular dystrophy
Muscular dystrophies (MDs) are a heterogeneous group of hereditary genetic diseases characterized by progressive degeneration of skeletal - and sometimes cardiac and smooth - muscle tissue, leading to muscle weakness and atrophy with variable progression depending on the form. All share a common anatomopathological basis: necrosis of muscle fibers, insufficient regeneration and progressive replacement of muscle by fibroadipative tissue. The gene involved, the mode of transmission and the deficient protein determine the clinical form, topography of the disease, severity and prognosis. Today, there are over 30 genetically distinct forms of muscular dystrophy, the main ones being Duchenne muscular dystrophy (DMD - X-linked, the most frequent and severe - 1/3,500 male births), Becker muscular dystrophy (BMD - allelic of DMD, milder form), myotonic dystrophy type 1 (DM1 - Steinert's disease - the most common adult disorder in Quebec, with an exceptional prevalence in the Saguenay-Lac-Saint-Jean region - 1/475 inhabitants - linked to a founder effect of the Quebec population), limb-girdle muscular dystrophy (LGMD - a heterogeneous group with over 30 subtypes), facioscapulohumeral dystrophy (FSHD) and Emery-Dreifuss dystrophy. Serum creatine kinase (CK) is the reference biological marker of muscle lysis: its elevation, sometimes massive (×10 to ×100 normal), is the first biological sign pointing to a primary muscle pathology. Diagnosis of certainty is based on a combination of molecular genetic analysis (sequencing of the gene involved - NGS panel of myopathies), muscle biopsy with immunohistochemical and immunofluorescent studies (muscle protein expression), and electromyography (EMG).
Main clinical forms
| Shape | Genetics, pathophysiology, and presentation | Diagnosis and treatment |
|---|---|---|
| Duchenne muscular dystrophy (DMD) 1/3 500 male births - X-linked |
Mutation of the DMD gene (Xp21.2 - the largest human gene, 2.4 Mb, 79 exons) → total absence of dystrophin (protein of the dystrophin-glycoprotein complex - DAG complex - ensures anchoring of the cytoskeleton to the extracellular matrix) → membrane instability → pathological calcium influx → muscle necrosis; X-linked recessive transmission (affected boys, driving mothers) - de novo mutations in 30 % of cases; onset between 2-5 years : delayed walking (walking after 18 months), frequent falls, difficulty running, difficulty climbing stairs; Gowers sign (boy stands up by leaning on his knees with his hands - evidence of weak hip extensors and quadriceps); calf pseudohypertrophy (replacement of muscle by adipose and connective tissue - bulky appearance but real weakness); loss of walking: 9-12 years untreated (13-15 years on corticosteroids); progressive scoliosis after loss of walking; dilated cardiomyopathy (DCM): present in 90 % after age 18 - leading cause of death; restrictive respiratory failure: FEV1 progressively decreases - non-invasive ventilation (NIV) then tracheostomy; mild cognitive impairment (mean IQ 85) and neurodevelopmental disorders (ADHD, autism - expression of DMD in the brain); CK ×50-100 normal (up to 50,000 IU/L) | Massive CK + myopathic EMG + biopsy (total absence of dystrophin in IHC/IF + Western blot) + genetics: NGS or MLPA panel (exonic deletions 65-70 %, duplications 5-10 %, point mutations 25-30 %); neonatal screening (CK on Guthrie card - programs in Quebec); treatment : corticosteroids (deflazacort or prednisone - delay loss of walking by 2-3 years, slow progression of cardiomyopathy and respiratory failure - standard of care since 1989); targeted therapies according to mutation: étéplirsen, casimersen, viltolarsen (exon skipping 51, 45, 53 by antisense - FDA approved); givinostat (HDAC inhibitor - FDA approval 2024); ataluren (Translarna - premature stop codon - EMA approval); golodirsen ; gene therapy (dys-micro-dystrophin - SRP-9001/delandistrogen moxeparvovec - FDA approval 2023 in <4 yrs); cardiac monitoring (annual echo + cardiac MRI - ACEI from onset CMD); nocturnal NIV from FVC <50 % or nocturnal SpO₂ <95 %; physiotherapy, occupational therapy, orthoses, nutritional monitoring |
| Becker muscular dystrophy (BMD) 1 in 18,000-30,000 male births. |
Same DMD gene — mutations maintaining the reading frame (in-frame deletions) → truncated but partially functional dystrophin (vs total absence in DMD); Monaco rule: out-of-frame deletion → severe DMD; in-frame deletion → milder BMD; variable onset: 5–15 years (cramps on exertion, exercise myoglobinuria in mild forms) to adulthood (proximal lower limb weakness); walking preserved until after 16 years (sometimes lifelong); dilated cardiomyopathy often more severe and earlier than muscle weakness in certain allelic forms of BMD (X-linked cardiomyopathy); very high CK (×5–50) even in mild forms | Muscle biopsy: dystrophin present but reduced in quantity or abnormal in size (vs total absence of DMD) — Western blot key to distinguish DMD vs BMD; genetics MLPA + DMD sequencing; treatment: corticosteroids if rapid progression; close cardiological monitoring (CMD often more threatening than muscle weakness) — ACE inhibitors/beta-blockers if CMD; implantable cardioverter-defibrillator (ICD) if ejection fraction <35 %; heart transplant discussed if refractory CMD |
| Myotonic dystrophy type 1 (DM1 - Steinert's disease) Prevalence Saguenay–Lac-Saint-Jean: 1/475 |
Unstable CTG triplet expansion in the DMPK gene (chromosome 19q13.3) - normal: 5-37 CTG repeats; mild DM1: 50-150; classic adult: 100-1,000; severe/congenital form: >1,000; genetic anticipation (increase in the number of repeats with each generation - worsening of the disease with each generation transmitted by the mother); mutant transcript accumulates in the nucleus → sequestration of MBNL proteins → aberrant alternative splicing of multiple genes → multisystem damage; myotonia (inability to release muscles quickly after contraction - handshake difficult to release, difficulty in opening hands after squeezing a cold object - hammer sign on thenar eminence); predominant distal weakness (finger extensors, foot lifters - steppage) + facial muscles (elongated face, ptosis, upturned lips - «shark face») + sternocleidomastoid muscles (thin neck - swan sign); systemic involvement: cardiac conduction disorder (atrioventricular block, arrhythmias - main cause of sudden death - annual Holter ECG ± pacemaker); T1DM and hypogonadism (60 % of men); cataract (star-shaped lens in lamp slit - 80 % after age 50); excessive daytime hypersomnia (somnolence - high Epworth score - hypothalamic dysfunction); cognitive disorders and apathetic personality; constipation, megacolon, gallstones (smooth muscle involvement); restrictive respiratory failure + sleep apneas | Molecular genetic testing: PCR + Southern blot (measurement of CTG repeat number) — gold standard — no muscle biopsy needed if typical clinical presentation; normal or moderately elevated CK (3-5x); annual ECG + Holter (atrio-ventricular block, ventricular tachycardia); brain MRI (leukoencephalopathy — subcortical T2 hyperintensities); symptomatic treatment for myotonia: mexiletine (sodium channel blocker — 150–300 mg 3x/day — strong recommendation) or lamotrigine; foot drop: AFO orthotics; somnolence: modafinil or methylphenidate; pacemaker if advanced conduction disorder (AVB > PR 280 ms or bifascicular block); genetic counseling (anticipation — risk of severe congenital form if mother affected and >1,000 CTGs) |
| Limb-girdle muscular dystrophies (LGMD) >30 subtypes — LGMD R and D |
Heterogeneous group (formerly classified as LGMD 1 and 2 — new 2018 nomenclature: LGMD R = recessive, LGMD D = dominant) of over 30 genetic subtypes affecting the pelvic and scapular girdles; most frequent: LGMD R1 (calpain-3 — chromosome 15); LGMD R2 (dysferlin — chromosome 2 — membrane repair); LGMD R5 (γ-sarcoglycan); LGMD R9 (FKRP — dystroglycanopathy); variable onset: childhood to adulthood; symmetrical weakness of pelvic girdle muscles (difficulty rising from a chair, climbing stairs) and scapular girdle muscles (difficulty raising arms) — waddling gait; variable CK depending on subtype (×5 to ×50 for dysferlinopathy); cardiomyopathy in some forms (LGMD R5–R8 sarcoglycanopathies); normal intelligence | NGS panel for myopathies (sequencing of CAPN3, DYSF, SGCA/B/G/D, FKRP, ANO5 genes, etc.) — often replaces biopsy as initial investigation; muscle biopsy (IHC + muscle protein panel) if genetics non-contributory; muscle MRI (mapping of muscle involvement pattern — helps to target gene for sequencing); no approved disease-modifying treatment specifically for LGMDs in 2025 — physiotherapy, occupational therapy, orthotics, cardiac and respiratory monitoring depending on subtype |
| Facioscapulohumeral muscular dystrophy (FSHD) 3rd muscular dystrophy in frequency - 1/20,000 |
Unique epigenetic mechanism: contraction of the number of D4Z4 repeats on chromosome 4q35 (FSHD1 - 95 % of cases) or SMCHD1 mutation (FSHD2 - 5 %) → hypomethylation → aberrant expression of the DUX4 gene (normally silent embryonic transcription factor) in adult muscle → muscle toxicity; autosomal dominant transmission (FSHD1); onset in adolescence or young adulthood (rarely before age 10); characteristic descending topography: facial muscles (difficulty closing eyes in sleep - lagophthalmos - wheezing, puffing cheeks, abnormal laughter) → scapular muscles (detachment of scapulae - scapula alata - inability to raise arms above shoulders) → abdominal muscles (Beevor's sign - umbilicus rises when trunk flexed) → lower limb muscles (tibialis anterior - steppage); frequent asymmetric involvement (characteristic); loss of walking in 20 %; hearing loss (high frequencies - 75 %); retinal telangiectasias and microaneurysms (Coats' disease); no significant cardiac involvement; normal or slightly elevated CK (×2-3) | Genetic testing: Southern blot + methylation analysis (D4Z4 repeat size — <11 repeat units on permissive 4qA allele — confirmatory); FSHD2: SMCHD1 sequencing + methylation; muscle biopsy rarely needed if genetic testing is confirmed; muscle MRI (asymmetric distribution, fat infiltration in affected muscles); no approved treatment as of 2025 — DUX4 inhibitor and gene therapy trials ongoing (givinostat, RG6206); physiotherapy, tibial braces, surgical scapular stabilization (scapulopexy) for significant functional impairment |
Diagnostic workup for myopathies
- Serum creatine kinase (CK): first marker to measure in case of suspected myopathy — normal values: male 30–200 U/L, female 30–170 U/L; in muscular dystrophies: slightly elevated (×2–5 — FSHD, DM1) to massively elevated (×50–100 — DMD, LGMD R2 dysferlinopathy); very high CK in obligate female carriers of DMD (50–70 % have elevated CK); CK may be normal in certain metabolic myopathies and congenital myopathies; transient elevation after intense exercise, trauma, or IM injection (false positives)
- Electromyography (EMG): distinguishes myopathic involvement (short, polyphasic, low-amplitude motor unit potentials - early recruitment) from neuropathic involvement (wide MUPs, denervation); detects electrical myotonia («dive bomber» sound with decremental myotonic discharges) - characteristic of DM1 and congenital myotonia
- Muscle MRI: precise mapping of the topography and severity of the involvement (T1 fat signal and STIR edema/inflammation) - guides the choice of biopsy site and suggests the type of dystrophy according to the pattern of involvement; increasingly used as a tool for monitoring progression
- Muscle biopsy: histological examination (hematoxylin-eosin — necrosis, regeneration, fibrosis, inflammatory infiltrate) + histochemistry (ATPase — fiber typing) + immunohistochemistry (IHC — dystrophin, sarcoglycans, dysferlin, calpain-3, merosin, collagen VI panel, etc.) + immunofluorescence + Western blot (protein quantification and size); muscle to biopsy: moderately affected muscle (not the weakest — advanced fibrosis, little contribution); guides genetic workup
- Molecular Genetic Analysis: Gold Standard of Diagnostic Certainty — MLPA (Exon Deletion/Duplication Detection — DMD/BMD); Triplet-Repeat PCR (DM1/DM2); Myopathy NGS Panel (Simultaneous Sequencing of >100 Genes — Becoming the First-Line Test in Many Centers Before Biopsy); Whole Exome or Whole Genome Sequencing if Panel is Non-Contributory
- Multisystemic assessment by phenotype: ECG + Holter + echocardiography (cardiomyopathy — DMD, DMB, DM1, LGMD sarcoglycanopathies); PFT + spirometry + polysomnography (restrictive respiratory insufficiency + apneas); swallowing EMG if dysphagia (DM1); ophthalmological assessment (cataracts — DM1; retinopathy — FSHD); cognitive and neuropsychological assessment
ℹ️
Quebec has a unique global prevalence of Myotonic dystrophy type 1 (Steinert's disease) in the region of Saguenay-Lac-Saint-Jean (1 in 475 inhabitants - 25 times the global prevalence) due to a founder effect: a common ancestor carrying the mutation arrived in New France in the 17th century, and their descendants populated the geographically isolated region. Neuromuscular Diseases Clinic of Jonquière (CMNM) is a global center of excellence for the care and research of DM1. Interdisciplinary Research Group on Neuromuscular Diseases (GRIMN) coordinates care and research in this region.
Urgent complications of muscular dystrophies
Dial 911 immediately in case of: acute respiratory distress (rapid worsening of dyspnea, SpO₂ <90 %, retractions, cyanosis) in a patient known to have muscular dystrophy with respiratory involvement — emergency initiation or adjustment of non-invasive ventilation (NIV); palpitations, syncope, or malaise in a patient with DM1 or myotonic dystrophy — risk of complete atrioventricular block or ventricular tachycardia; myoglobinuria (cola-red-brown urine) after exertion or general anesthesia in a patient with known very high CK — risk of acute kidney injury due to rhabdomyolysis.
Significant anesthetic risk: Patients with muscular dystrophy are at high risk for complications during general anesthesia (malignant hyperthermia with halogenated agents, rhabdomyolysis with succinylcholine, cardiac and respiratory decompensation) — any MD patient should wear a medical alert card and inform any physician or dentist of their diagnosis.
Consult at Clinique Omicron
Clinique Omicron physicians evaluate patients presenting with progressive muscle weakness, prescribe first-line investigations (CK, EMG, genetic panel), refer to a neurologist specializing in neuromuscular diseases, and ensure coordination of multidisciplinary care (cardiology, pulmonology, physiotherapy, medical genetics, genetic counseling). For Quebec patients with Steinert's myotonic dystrophy, a referral to the Jonquière Neuromuscular Disease Clinic can be facilitated. Consultations are available at our service points in Quebec, as well as via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not substitute for the advice of a qualified healthcare professional. The diagnosis and management of muscular dystrophies require a multidisciplinary team specializing in neuromuscular diseases.
Omicron Clinic
Need to consult a doctor?
Treatment within 24-48 hours. In-clinic or telemedicine, anywhere in Quebec.
Insurance receipts. 7j/7. No family doctor required.