Overview And Classification
Muscular dystrophies are a heterogeneous group of genetically determined disorders characterised by progressive degeneration of skeletal muscle. While Duchenne and Becker muscular dystrophies are the most common X-linked dystrophinopathies, several other primary muscular dystrophies present in pediatric practice with distinct clinical phenotypes, inheritance patterns, and genetic loci.
Genetic And Inheritance Profile
| Disease | Mode Of Inheritance | Gene Location | Gene Product |
|---|---|---|---|
| Limb Girdle Muscular Dystrophy (LGMD) | AR / AD | 5q / 15q | Sarcoglycans |
| Congenital Muscular Dystrophies (CMD) | AR | 6q2 / 8q31 | Merosin / Fukutin |
| Myotonic Dystrophies | AD | 19q (CTG repeats) | DM, 2FN9 |
| Facioscapulohumeral Dystrophy (FSHD) | AD | 4q35 | D4Z4 macrosatellite |
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Limb Girdle Muscular Dystrophies (LGMD)
Pathophysiology And Clinical Features
- LGMD represents a group of clinically heterogeneous syndromes with either autosomal dominant (AD) or autosomal recessive (AR) inheritance.
- Childhood-onset forms predominantly present with lower extremity proximal muscle weakness.
- Autosomal recessive limb girdle dystrophies exhibit an earlier onset, more rapid progression, and significantly higher serum creatine kinase (CK) values compared to dominant forms.
- Cardiac and systemic involvement is highly variable depending on the specific genetic subtype.
Investigations And Management
- Serum CK is modestly elevated in most forms but can be markedly high in sarcoglycanopathies, dysferlinopathy, and caveolinopathy.
- Diagnosis requires genetic testing or muscle biopsy with specific immunohistochemistry (e.g., staining for sarcoglycans).
- Treatment remains entirely symptomatic and supportive.
Congenital Muscular Dystrophies (CMD)
Pathophysiology And Clinical Features
- CMD comprises distinct heterogeneous diseases of genetic origin, invariably present at birth or within the first year of life.
- Inheritance is autosomal recessive.
- Infants present with severe hypotonia, delayed motor milestones, bulbar dysfunction, respiratory insufficiency, and static or slowly progressive weakness.
- Trunk and extremities demonstrate significant wasting.
- Early onset of contractures and joint deformities (arthrogryposis) is a major clinical hallmark.
Subtypes And Investigations
- Classification: Divided broadly into Merosin-negative CMD and Merosin-positive CMD based on muscle immunohistochemistry.
- Fukuyama Type CMD: A severe variant resulting from Fukutin mutations, characterised by severe muscle symptoms, prominent brain MRI changes (cerebral dysgenesis), and profound developmental delay.
- Diagnosis: Supported by dystrophic myopathic features on muscle biopsy, elevated CK levels, cardiac assessment, and brain imaging.
Myotonic Dystrophies
Myotonic Dystrophy Type 1 (Classic Form)
- Caused by an abnormal expansion of trinucleotide (CTG) repeats (>80) in the DMPK gene on chromosome 19.
- Inherited in an autosomal dominant pattern with anticipation (increasing severity in successive generations).
- Clinical Presentation: Muscle weakness is predominantly distal (proximal muscles involved later). Features include a long expressionless face, facial dysmorphism, frontal baldness, and temporal muscle wasting.
- Myotonia: The unique diagnostic hallmark is delayed relaxation of muscle after a hand grip or after percussion.
- Multisystem Involvement: Includes iridescent spoke-like posterior capsular cataracts, endocrinopathies (diabetes mellitus, hyperinsulinism, testicular atrophy), immune deficiencies (low IgA), and cardiac arrhythmias.
Congenital Myotonic Dystrophy
- The most severe phenotype, almost exclusively inherited from an affected mother.
- Prenatal Features: Decreased fetal movements and polyhydramnios.
- Neonatal Presentation: Profound hypotonia, facial diplegia (tent-like mouth), neonatal respiratory distress, severe feeding difficulties, and club foot.
- Nuance: Clinical myotonia is noticeably absent in neonates and infants; the diagnosis often relies on demonstrating myotonia (clinical or electromyographic) in the mother.
Investigations And Management
- Electromyography (EMG): Confirms myotonia, demonstrating a characteristic ‘revving engine’ sound, though it may show an amyopathic pattern in congenital forms.
- Treatment: Medications blocking sodium channels (procainamide, phenytoin, mexiletine, carbamazepine) or tricyclic antidepressants reduce myotonia. Cardiac monitoring is strictly essential as progressive cardiac disease is a frequent cause of death.
Facioscapulohumeral Muscular Dystrophy (FSHD)
Pathophysiology And Clinical Features
- An autosomal dominant disorder caused by the shortening of the macrosatellite repeat D4Z4 on allele 4q35.
- Pattern Of Weakness: Uniquely presents with marked asymmetric weakness.
- Progression starts with facial weakness (inability to completely close eyes), followed by scapular fixators (asymmetric scapular winging), humeral, truncal, and lower limb muscles.
- Popeye Arm Appearance: Biceps and triceps are typically wasted and weak, whilst the deltoid and forearm muscles are completely spared.
- Beevor Sign: Lower abdominal muscles are significantly weaker than upper abdominal muscles, causing the umbilicus to move upwards upon neck flexion.
Systemic Associations
- Non-muscular manifestations include high-frequency sensorineural hearing loss, Coats disease (retinal telangiectasia, exudation, and detachment), restrictive respiratory disease, and atrial arrhythmias.