What are the differential diagnoses for a neonate presenting with unilateral eye palsy and a hairy ear?

Differential Diagnosis of Unilateral Eye Palsy with Hairy Ear in a Neonate

The combination of unilateral eye palsy and hairy ear in a neonate should immediately raise suspicion for CHARGE syndrome, which requires urgent evaluation for life-threatening cardiac malformations and comprehensive genetic testing with CHD7 sequencing. 1

Primary Consideration: CHARGE Syndrome

CHARGE syndrome is the most critical diagnosis to exclude given the constellation of eye abnormalities (coloboma causing apparent palsy) and ear anomalies (hairy/malformed pinna). 1 This syndrome requires:

• Immediate ophthalmologic examination to assess for coloboma, a cardinal CHARGE feature that may present as apparent eye movement limitation 1
• Urgent cardiac evaluation to identify life-threatening cardiovascular malformations, especially critical in the first year of life 1
• CHD7 gene sequencing as first-line genetic testing, with positive results in approximately 60% of cases 1
• Comprehensive audiologic testing to document hearing loss type and severity 1
• Renal ultrasound to screen for associated genitourinary anomalies 1
• Head MRI to assess for semicircular canal abnormalities and neurological involvement 1

Congenital Cranial Dysinnervation Disorders (CCDDs)

If CHARGE is excluded, consider isolated developmental defects of cranial nerves:

Isolated Congenital Facial/Ocular Nerve Aplasia or Hypoplasia

• MRI of the posterior fossa and CT of the temporal bone are essential, as imaging reveals the underlying cause in 80% of cases, showing ipsilateral facial nerve aplasia or hypoplasia 2
• These findings point toward an underlying developmental defect occurring outside syndromic contexts 2
• CCDDs arise from primary defects of cranial nucleus/nerve development or guidance, requiring neuro-imaging and/or genetic investigations for diagnostic confirmation 3

Unilateral Multiple Cranial Neuropathy

• Consider involvement of cranial nerves V, VII, IX, X, and XII with ipsilateral brainstem hypoplasia 4
• Vascular malformation in utero leading to brainstem ischemia is the proposed mechanism 4
• This may represent a unilateral variant sharing etiology with Möbius syndrome 4

Congenital Third Nerve Palsy

• Unilateral pupil-sparing third nerve palsy can occur with prenuclear dysinnervation involving otolithic pathways 5
• May present with exotropia and novel dysinnervation patterns including synergistic divergence 5
• Associated systemic findings (cryptorchidism, renal aplasia) may suggest overlapping phenotypes with Duane-radial ray or acro-renal-ocular syndromes 5

Acquired/Traumatic Causes

Birth Trauma

• Approximately 40-75% of unilateral facial paralysis cases in children remain idiopathic, but birth trauma must be excluded 6
• Delivery-related trauma can cause congenital facial nerve palsy 6

Perinatal Complications

• Prematurity, asphyxia, and complicated perinatal courses account for approximately 10% of neurological deficits 7
• Risk factors include NICU stay exceeding 5 days, ECMO, assisted ventilation, and hyperbilirubinemia requiring exchange transfusion 7

Infectious Etiologies

• Congenital rubella, syphilis, toxoplasmosis, and herpes are prenatal infections associated with cranial nerve palsies 7
• Culture-positive postnatal bacterial and viral meningitis is a risk factor for delayed-onset neurological deficits 7

Structural/Anatomic Associations

• Craniofacial anomalies involving the pinna, ear canal, ear tags, and ear pits are associated with underlying neurological abnormalities 7
• The hairy ear finding specifically suggests dysmorphic features requiring systematic evaluation for syndromic diagnoses 1

Critical Diagnostic Pitfalls

Do not delay cardiac evaluation while pursuing other workup, as CHARGE-associated cardiac malformations are life-threatening 1. Do not assume isolated traumatic etiology without comprehensive imaging, as 80% of developmental defects are identified only through MRI/CT 2. Do not rely on family history to exclude genetic causes, as over 90% of children with autosomal recessive conditions are born to unaffected parents 7.

Recommended Diagnostic Algorithm

1. Immediate cardiac evaluation and ophthalmologic examination to exclude CHARGE syndrome 1
2. CHD7 genetic testing as first-line investigation 1
3. MRI posterior fossa and CT temporal bone if CHARGE excluded, to identify cranial nerve aplasia/hypoplasia 2
4. Comprehensive audiologic testing and renal ultrasound regardless of suspected etiology 1
5. Multidisciplinary assessment with ENT, pediatric neurology, ophthalmology, genetics, and cardiology 1, 2