FSHD & LGMD
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facioscapulohumeral muscular dystrophy AND limb girdle muscular dystrophy
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Facioscapulohumeral Muscular Dystrophy (FSHD) & Limb-Girdle Muscular Dystrophy (LGMD)
FSHD
Overview & Epidemiology
FSHD is the third most common hereditary myopathy, with a prevalence of ~5 per 100,000. It typically presents in childhood or young adulthood (age 6-20), though adult-onset cases occur. Inheritance is autosomal dominant. Two genetically distinct subtypes exist:
- FSHD1 (~95%): deletions of tandem 3.3-kb repeat units at 4q35, reducing the D4Z4 repeat array to <35 kb
- FSHD2 (~5%): no deletion; instead, mutations in SMCHD1 (most common), DNMT3B, or LRIF1 genes
Both subtypes share the same final mechanism - the D4Z4 region becomes hypomethylated, permitting toxic re-expression of the DUX4 gene (which encodes a transcription factor normally silenced after early development). DUX4 overexpression dysregulates downstream gene expression, leading to muscle fiber death. FSHD1 and FSHD2 are clinically and histopathologically identical.
Clinical Features
FSHD has a characteristic descending pattern of weakness:
| Region | Specific Findings |
|---|---|
| Face | Inability to smile, whistle, or firmly close eyes; orbicularis oculi + oris involved; masseters/extraocular muscles spared |
| Shoulder | Scapular winging ("angel-wing" appearance), loss of scapular stabilizers, difficulty raising arms; biceps/triceps affected but deltoid relatively spared |
| Arms | Wrist extension > wrist flexion weakness |
| Legs | Anterior compartment weakness → foot drop |
| Pelvis | 20% of patients eventually develop pelvic girdle weakness → wheelchair dependency |
Extra-muscular features:
- Ventilatory muscle weakness: ~5%
- Sensorineural hearing loss (increased incidence)
- Coats' disease: retinal telangiectasias, exudation, and retinal detachment
- Heart is generally not involved (distinguishes FSHD from many other dystrophies)
Labs & Investigations
- Serum CK: normal or mildly elevated
- EMG: nonspecific myopathic pattern
- Muscle biopsy: nonspecific dystrophic changes; can show prominent inflammatory infiltrate - may be misdiagnosed as myositis
- Genetic testing: diagnosis confirmed by D4Z4 repeat size analysis (FSHD1) or SMCHD1/DNMT3B/LRIF1 sequencing (FSHD2)
Treatment
Currently no disease-modifying therapy is approved. Clinical trials targeting DUX4 expression suppression are ongoing. Current management:
- Physical and occupational therapy
- Ankle-foot orthoses (AFO) for foot drop
- Scapular fixation surgery: improves winging and function
- Respiratory monitoring (spirometry) for the 5% with ventilatory involvement
Limb-Girdle Muscular Dystrophy (LGMD)
Overview & Epidemiology
LGMDs are a genetically heterogeneous group of dystrophies affecting males and females equally. Onset ranges from late first decade to fourth decade of life. Prevalence: ~1.63 per 100,000 (range 0.56-5.75 per 100,000). The group is defined by:
- Progressive proximal (pelvic and shoulder girdle) weakness
- Independent ambulation achieved at some point
- Elevated CK
- Dystrophic features on biopsy or imaging
- At least two unrelated families reported with the same mutation
Classification - ENMC Nomenclature (2018)
The older system used LGMD1 (autosomal dominant) and LGMD2 (autosomal recessive) with alphabetical suffixes. The modern ENMC system uses:
- LGMDD (Dominant) + number
- LGMDR (Recessive) + number
Key subtypes:
| Old Name | New Name | Gene/Protein | Key Feature |
|---|---|---|---|
| LGMD2A | LGMDR1 | CAPN3 / Calpain-3 | Most common; scapular winging; no cardiac/respiratory involvement; common in Southern Europe |
| LGMD2B | LGMDR2 | DYSF / Dysferlin | Calf-predominant initially (Miyoshi myopathy overlap) |
| LGMD2C-F | LGMDR3-6 | Sarcoglycans (γ, α, β, δ) | Sarcoglycanopathies; can resemble DMD |
| LGMD2I | LGMDR9 | FKRP / Fukutin-related protein | Common in northern Europeans; calf hypertrophy; cardiac + respiratory involvement |
| LGMD2L | LGMDR12 | ANO5 / Anoctamin-5 | ~7% of LGMD in the US; medial calf atrophy; overlaps with dysferlinopathy pattern |
| LGMD1B | LGMDD1 | LMNA / Lamin A/C | Now reclassified under EDMD; cardiac conduction defects prominent |
Note: Laminopathies (old LGMD1B) and myofibrillar myopathies (old LGMD1A/myotilin) are now reclassified out of LGMD into EDMD and MFM groups respectively under the ENMC system.
Clinical Features
- Progressive proximal weakness of pelvic + shoulder girdle muscles
- Often clinically indistinguishable from Duchenne/Becker muscular dystrophy
- Respiratory insufficiency from diaphragm weakness - variable by subtype
- Cardiomyopathy - variable by subtype (prominent in LGMDR9/FKRP, laminopathies)
- Serum CK elevated (often markedly)
- EMG: myopathic
- Muscle biopsy: dystrophic features + immunohistochemistry (sarcoglycans, dysferlin, α-dystroglycan) helps narrow subtype
Critical diagnostic point: Immune-mediated necrotizing myopathy (IMNM) can mimic LGMD both clinically and histopathologically. Any suspected LGMD without a confirmed pathogenic mutation should be screened for anti-HMGCR and anti-SRP antibodies - these indicate a treatable autoimmune condition.
Diagnosis
Definitive diagnosis requires genetic testing (next-generation sequencing panel). Immunohistochemistry on biopsy can guide pre-genetic workup. The protein interaction map below shows where the relevant proteins reside within the muscle fiber architecture:
Treatment
- No curative therapy for most subtypes
- Pompe disease (acid maltase deficiency, formerly LGMD2V/LGMDR22): enzyme replacement therapy (alglucosidase alfa) is available and effective - the only LGMD subtype with approved disease-modifying therapy
- Physical therapy, respiratory support (NIV when needed), cardiac surveillance and management (ACE inhibitors/beta-blockers for cardiomyopathy)
- Regular cardiac monitoring especially for LGMDR9 (FKRP), laminopathies, and sarcoglycanopathies
FSHD vs LGMD - Key Comparisons
| Feature | FSHD | LGMD |
|---|---|---|
| Pattern | Facial + scapulohumeral + descending | Proximal pelvic + shoulder girdle |
| Inheritance | Autosomal dominant (AD) | AD (LGMDD) or AR (LGMDR); AR more common |
| Genetics | D4Z4 deletion at 4q35 (FSHD1); SMCHD1/DNMT3B/LRIF1 (FSHD2) | Heterogeneous: calpain-3, dysferlin, sarcoglycans, FKRP, anoctamin-5, etc. |
| Facial weakness | Yes - hallmark | No |
| Cardiac | Typically spared | Yes, in several subtypes (FKRP, laminopathies) |
| Respiratory | ~5% | Variable; prominent in some subtypes |
| CK | Normal to mildly elevated | Markedly elevated |
| Hearing loss | Yes (increased incidence) | No |
| Coats' disease | Yes | No |
| Disease-modifying Rx | None (DUX4 trials ongoing) | ERT for Pompe; none for others |
| Scapular winging | Prominent, early | Can occur in calpainopathy; less prominent |
Sources: Harrison's Principles of Internal Medicine 22E (2025), Adams and Victor's Principles of Neurology 12th Ed - FSHD and LGMD sections; Bradley and Daroff's Neurology in Clinical Practice - LGMD in pregnancy
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Your presentation is ready! Here's the download link:
FSHD LGMD
Presentation · PPTX
What's inside (11 slides):
| Slide | Content |
|---|---|
| 1 | Title slide - dark navy with teal/coral accent design |
| 2 | Agenda / overview of both topics |
| 3 | FSHD section divider |
| 4 | FSHD Genetics - FSHD1 (D4Z4 deletion) vs FSHD2 (SMCHD1/DNMT3B/LRIF1) with DUX4 mechanism |
| 5 | FSHD Clinical features (descending weakness pattern), extra-muscular features, investigations, management |
| 6 | LGMD section divider |
| 7 | LGMD ENMC 2018 classification + full subtype table (LGMDR1-R12) |
| 8 | LGMD clinical features, diagnosis, diagnostic pitfall (IMNM), management |
| 9 | FSHD vs LGMD comparison table |
| 10 | High-yield clinical pearls (6 key take-home points) |
| 11 | Closing key takeaways slide |
Design uses a deep navy background with teal for FSHD and coral/red for LGMD throughout, so both conditions are visually distinct.
Ppt with images
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Your image-rich presentation is ready!
FSHD LGMD with images
Presentation · PPTX
What's in it (12 slides with real textbook images):
| Slide | Content | Images |
|---|---|---|
| 1 | Title slide | FSHD & LGMD body weakness diagrams side-by-side |
| 2 | FSHD section divider | Clinical patient photo (scapular winging + lumbar lordosis) |
| 3 | FSHD Genetics — FSHD1 vs FSHD2, DUX4 mechanism | — |
| 4 | FSHD Clinical features — descending weakness pattern | FSHD muscle distribution diagram |
| 5 | FSHD Management — surgery, PT, AFO | Bilateral scapulothoracic arthrodesis X-ray |
| 6 | LGMD section divider | LGMD proximal weakness body diagram |
| 7 | LGMD ENMC 2018 classification + subtypes table | — |
| 8 | LGMD Protein Map (full-width) | Full Harrison's protein interaction diagram (sarcolemma, sarcomere, nucleus) |
| 9 | LGMD Clinical features, diagnosis, Pompe ERT | — |
| 10 | FSHD vs LGMD comparison table | — |
| 11 | 6 high-yield clinical pearls | — |
| 12 | Key takeaways closing slide | Faint overlay of both body diagrams |
All images are sourced directly from Harrison's 22E (2025) and Campbell's Operative Orthopaedics 15E (2026).
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FSHD LGMD with images
Presentation · PPTX
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FSHD LGMD
Presentation · PPTX
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