Muscle Disorders (Myopathies)

This chapter covers muscle disorders other than the dystrophinopathies; Duchenne and Becker are discussed in a separate chapter.

Congenital muscular dystrophies

A heterogeneous group beginning at birth or in the first months, with moderately raised creatine kinase and dystrophic changes on biopsy.

• Merosin (laminin alpha-2) deficiency: severe hypotonia, joint contractures and diffuse white matter signal change on brain imaging. The white matter involvement is usually clinically silent and is a diagnostic clue.
• Collagen VI-related disorders (Ullrich and Bethlem): the combination of proximal contractures with distal joint hyperlaxity, follicular hyperkeratosis and a tendency to keloid. Ullrich is the severe and Bethlem the mild end of a continuum.
• Dystroglycanopathies (FKRP, POMT1, POMT2, FKTN): muscle involvement may be accompanied by brain malformation and eye involvement; Walker-Warburg syndrome and muscle-eye-brain disease are the severe ends.
• SEPN1-related myopathy: early and disproportionate respiratory failure with spinal rigidity. A child who still walks but requires nocturnal respiratory support should raise this possibility.

Congenital myopathies

Congenital disorders that are generally non-progressive or very slowly progressive, with characteristic structural changes on biopsy. Creatine kinase is normal or mildly raised. Shared features include a long face, high-arched palate, ophthalmoparesis in some subtypes, spinal deformity, and respiratory involvement that may be out of proportion to skeletal muscle involvement.

• Nemaline myopathy (NEB, ACTA1): prominent facial involvement with bulbar and respiratory involvement to the fore.
• Core myopathies (RYR1, SELENON): RYR1-related cases carry a risk of malignant hyperthermia and this must be known before anaesthesia.
• Centronuclear and myotubular myopathies (X-linked MTM1, DNM2, BIN1): the X-linked form presents in the newborn with severe hypotonia, ophthalmoplegia and respiratory failure.

Myotonic dystrophy type 1

An autosomal dominant multisystem disorder due to a CTG repeat expansion in the DMPK gene. It shows anticipation: the repeat lengthens across generations and the disease appears earlier and more severely. The congenital form is almost always maternally transmitted.

• Congenital form: polyhydramnios, reduced fetal movement, severe hypotonia and respiratory failure at birth, facial weakness with a tented upper lip, sucking difficulty, talipes.
• Myotonia is ABSENT in the newborn period and appears in later childhood.
• In infants who survive the period of respiratory support motor function improves over time; learning difficulty and intellectual disability dominate the long-term picture.
• Multisystem involvement: cardiac conduction disease (with a risk of sudden death, requiring regular ECG surveillance), cataract, insulin resistance, gastrointestinal dysmotility, excessive daytime sleepiness, anaesthetic sensitivity.

Limb-girdle muscular dystrophies

A genetically heterogeneous group presenting with predominantly proximal weakness. Autosomal recessive forms are more frequent where consanguinity is common; sarcoglycanopathies and calpainopathy are relatively frequently reported in Türkiye. Creatine kinase is usually raised and diagnosis is by panel or exome sequencing. Cardiac involvement is prominent in some subtypes, particularly FKRP, LMNA and the sarcoglycanopathies, and requires surveillance.

Metabolic myopathies

These present with exercise intolerance, cramps, myalgia and rhabdomyolysis. The discriminating question is what kind of exertion provokes the symptoms.

• Short, intense exertion (sprinting, lifting): glycogen storage disorders; the second-wind phenomenon is typical of McArdle disease.
• Prolonged low-intensity exertion, fasting, fever or cold: fatty acid oxidation disorders, most often CPT2 deficiency.

Mitochondrial disorders

Muscle involvement may be part of multisystem mitochondrial disease. Suggestive features include exercise intolerance, ophthalmoplegia and ptosis, hearing loss, seizures, stroke-like episodes, raised lactate, multi-organ involvement and a matrilineal inheritance pattern. Diagnosis is by mitochondrial and nuclear gene analysis and, in selected cases, muscle biopsy with respiratory chain enzyme analysis.

Facioscapulohumeral muscular dystrophy

Autosomal dominant, arising from contraction of the D4Z4 repeat array at 4q35 (type 1) or from mutations in genes such as SMCHD1 (type 2), leading to inappropriate expression of DUX4 in muscle.

• Facial involvement is early and prominent: the eyes do not close fully in sleep, the child cannot whistle or drink through a straw, and the smile appears horizontal.
• Scapular winging and inability to raise the arm above head height are typical.
• Asymmetry is the signature of this disease and distinguishes it from other muscular dystrophies.
• Childhood-onset forms are more severe; sensorineural hearing loss and retinal vasculopathy may be associated, so hearing and fundus assessment are required.
• D4Z4 contraction is not detected by standard sequencing; a dedicated method is required and must be requested separately.

Muscle channelopathies

Episodic disorders due to mutations in genes encoding muscle membrane ion channels. Examination between attacks may be normal, so the history carries the diagnosis.

• Hypokalaemic periodic paralysis (CACNA1S, SCN4A): attacks lasting hours, provoked by carbohydrate-rich meals, rest after intense exercise and sleep.
• Hyperkalaemic periodic paralysis (SCN4A): shorter attacks triggered by fasting, cold and potassium-rich foods; myotonia may be present.
• Myotonia congenita (CLCN1): muscle stiffness that improves with warming up.
• Paramyotonia congenita (SCN4A): worsening with exercise and triggering by cold.
• These conditions are treatable and may carry anaesthetic risk; in a history of episodic weakness the investigation should continue even if examination is normal.

Juvenile dermatomyositis

The most common acquired inflammatory myopathy of childhood and one that must not be missed because it is treatable. Symmetrical proximal weakness is accompanied by characteristic skin findings: heliotrope rash of the eyelids, Gottron papules, nailfold capillary changes and calcinosis. Creatine kinase may be raised or normal; muscle MRI oedema, myositis-specific antibodies and, in selected cases, biopsy support the diagnosis. Treatment is based on corticosteroids and methotrexate; early and adequate treatment is decisive in preventing lasting problems such as calcinosis.