Clinical Assessment and the Diagnostic Pathway

This chapter sets out the clinical steps of the diagnostic process and the order in which investigations should be requested.

Key points in the history

• Prenatal: reduced fetal movement, polyhydramnios, intrauterine growth restriction, congenital contractures.
• Perinatal: hypotonia, weak cry, feeding difficulty, respiratory support, nasogastric feeding.
• Motor development: ages for head control, sitting, crawling and walking recorded separately; is this delay, plateau or loss?
• Family history: consanguinity, a similarly affected sibling, unexplained infant death, difficulty releasing the grip in the mother, early cardiac death or pacemaker in the family.
• Fatigability and diurnal variation — these are not volunteered unless asked directly.

What to look for on examination

• Observation: how the child enters the room, sits, and rises from the floor (Gowers); waddling gait, toe walking, scapular winging.
• In the infant: traction response, ventral and vertical suspension, frog-leg posture.
• Strength (MRC) and distribution: proximal or distal, symmetrical or asymmetrical, facial involvement.
• Deep tendon reflexes; generalised areflexia is a strong indicator of peripheral involvement.
• Muscle bulk: atrophy or pseudohypertrophy.
• Tongue fasciculations — look while the tongue rests in the mouth and the child is not crying.
• Breathing pattern, chest wall shape, cough strength.
• Spine, hips, contractures, pes cavus.

Creatine kinase

This is the cheapest and highest-yield single test in neuromuscular assessment. Values in the thousands suggest dystrophinopathy, limb-girdle dystrophies, inflammatory myopathy or rhabdomyolysis; moderate elevation suggests congenital muscular dystrophies and some metabolic myopathies; a normal or mildly raised value is consistent with SMA, neuropathies, junction disorders and most congenital myopathies.

• Creatine kinase rises after exercise, falls, intramuscular injection, electromyography and seizures; a questionable value should be repeated after rest.
• A normal creatine kinase does not exclude muscle disease.
• In advanced dystrophinopathy creatine kinase falls as muscle bulk is lost and may approach the normal range.

The current role of electrophysiology

With the spread of genetic testing the role of electromyography in children has narrowed. It is not required when the clinical picture is clear, as in typical SMA or typical Duchenne. It is most valuable today in suspected junction disorders, in the recognition and differentiation of acquired neuropathy, in separating demyelinating from axonal neuropathy to guide genetic testing, and in uncertain presentations where genetic testing has been unrevealing.

Genetic testing strategy

• Targeted single-gene testing when the picture is typical: SMN1 exon 7 deletion analysis with SMN2 copy number in suspected SMA; DMD deletion-duplication analysis in suspected Duchenne or Becker; DMPK CTG repeat analysis in congenital myotonic dystrophy; PMP22 copy number in demyelinating neuropathy.
• A panel when the picture points to a group but not a gene: congenital myopathy, limb-girdle, congenital myasthenic syndrome, hereditary neuropathy panels.
• Exome or genome sequencing when the picture is atypical, the panel is negative, or there is multisystem involvement.

Muscle biopsy and muscle MRI

Biopsy is now reserved for selected situations: when genetic testing has been unrevealing, when the pathogenicity of a variant of uncertain significance needs to be demonstrated, when inflammatory myopathy is suspected, and when respiratory chain enzyme analysis is required in suspected mitochondrial disease. A muscle that is involved but not end-stage should be selected. Muscle MRI shows the pattern of involvement and helps in selecting the biopsy site and in interpreting uncertain genetic findings; it does not replace genetic testing.

Newborn screening

Spinal muscular atrophy is included in the national newborn screening programme of the Turkish Ministry of Health and is tested from the heel-prick sample. According to Ministry figures an average of 150 infants are born with SMA in Türkiye each year. The clinical significance of screening is considerable: outcomes differ when treatment is started before motor neuron loss has occurred.

Conditions that mimic neuromuscular disease

Not every child presenting with weakness or hypotonia has a disorder of the motor unit. The following are common, mostly treatable, and when missed lead to an unnecessary diagnostic process.

• Joint hypermobility and benign congenital hypotonia — lax joints but NORMAL strength.
• Hypothyroidism and rickets — excluded by simple tests, and years are lost when missed.
• Hypokalaemia, hypercalcaemia, vitamin D deficiency, adrenal insufficiency.
• Severe anaemia, zinc and B12 deficiency, malnutrition, chronic kidney disease.
• Juvenile idiopathic arthritis — the child may be in pain rather than weak.
• Prader-Willi syndrome, Down syndrome, connective tissue disorders.
• The hypotonic phase of cerebral palsy, structural brain anomalies, spinal cord pathology.
• Drugs and toxins: corticosteroid myopathy, statins, colchicine, vincristine neuropathy.
• Functional neurological disorder in adolescents — diagnosed on positive findings, not by exclusion.