Can Congenital Lower Nerve Dysfunction (CLND) present unilaterally in a 2-month-old patient?

Congenital Hypomyelinating Neuropathy Can Present Unilaterally in a 2-Month-Old

Congenital hypomyelinating neuropathy typically presents bilaterally in neonates, but unilateral or asymmetric presentations can occur in the first months of life, particularly in cases of unilateral brain lesions or atypical peripheral neuropathy variants.

Typical Presentation Pattern

Congenital hypomyelinating neuropathy classically presents at birth with:

• Generalized bilateral hypotonia and weakness affecting all extremities from birth 1, 2
• Absent or markedly decreased deep tendon reflexes bilaterally 1, 2
• Severe motor nerve conduction velocity slowing on electrodiagnostic studies 1
• Respiratory compromise including diaphragmatic paralysis and poor respiratory effort 2
• Feeding difficulties with poor suck and swallow 1

The pathology shows large axons without myelin or with insufficient myelin for their diameter on nerve biopsy 1, 2.

Unilateral and Asymmetric Presentations

While bilateral involvement is the rule, asymmetric or unilateral presentations can occur:

• Unilateral brain lesions in preterm infants (such as unilateral intraparenchymal echodensity) initially produce bilateral abnormal neurological signs, but asymmetry of distal segmental movements emerges by 9-16 weeks postterm (2-4 months corrected age) 3
• Asymmetries become apparent after term age in infants with unilateral brain pathology, with reduced movements on the side contralateral to the lesion 3
• Congenital sensory neuropathies can present with generalized lack of sensory appreciation, hypotonia, and areflexia, sometimes with asymmetric involvement 4

Critical Diagnostic Considerations at 2 Months

At 2 months of age, you must distinguish between:

1. True congenital hypomyelinating neuropathy - which should show bilateral involvement from birth, though clinical improvement can occur in a cephalocaudal direction over the first 4 months 1

2. Unilateral brain lesions - which initially appear bilateral but develop clear asymmetry by 2-4 months, particularly affecting distal segmental movements 3

3. Hereditary sensory neuropathies - which can have variable presentations including asymmetric involvement, particularly affecting lower extremities more than upper 5

Diagnostic Workup

For a 2-month-old with suspected unilateral nerve dysfunction:

• Nerve conduction studies will show marked slowing of motor conduction velocities (often absent responses distally) and normal or mildly abnormal sensory responses in true hypomyelinating neuropathy 1, 2
• Needle electromyography may show normal proximal muscles but active denervation distally in a length-dependent pattern 2
• Neuroimaging is essential to exclude unilateral brain lesions (intraparenchymal echodensity, stroke, malformations) that can mimic peripheral neuropathy 3
• Sural nerve biopsy demonstrates scattered axons with very thin myelin sheaths and nearly complete loss of large diameter myelinated fibers without onion bulb formations 2

Important Clinical Pitfalls

• Do not assume bilateral disease excludes unilateral brain pathology - unilateral brain lesions produce bilateral abnormal signs initially, with asymmetry emerging only after 2 months 3
• Absence of asymmetry at birth does not rule out future unilateral presentation - asymmetries in movement quality become apparent during the 9-16 week postterm period 3
• Normal mental abilities do not exclude severe peripheral neuropathy - cognitive function is typically preserved in congenital hypomyelinating neuropathy and hereditary sensory neuropathies 5, 2

Prognosis

• Some cases show spontaneous improvement with normalization of motor nerve conduction velocities and clinical examination by 4 months, though deep tendon reflexes may remain absent 1
• Progressive cases remain profoundly hypotonic and ventilator-dependent, though cognitive development proceeds normally 2
• Unilateral brain lesions predict hemiplegia in 75% of cases when asymmetry of distal movements is present at 2-4 months 3