What is the diagnosis and management for a child with almond eyes and doll-like facies (facial features)?

Diagnosis: Cornelia de Lange Syndrome

A child presenting with almond-shaped eyes and doll-like facies should be evaluated for Cornelia de Lange Syndrome (CdLS), which is the most likely diagnosis and requires immediate genetic testing and multisystem assessment. 1

Key Diagnostic Features

Characteristic Facial Findings

• Almond-shaped palpebral fissures are a hallmark feature that distinguishes CdLS from other genetic conditions 1
• Doll-like facies includes:
  • Thin vermilion border of the upper lip 1
  • Long, smooth philtrum 1
  • Arched eyebrows that meet in the midline (synophrys) 1
  • Low-set ears 1
  • Small, down-turned mouth 1

Growth Parameters to Document

• Height and weight measurements (typically ≤10th percentile) 1
• Head circumference (often ≤10th percentile, indicating microcephaly) 1
• Prenatal and postnatal growth restriction is common 1

Associated Findings to Assess

• Limb anomalies: Look for oligodactyly, clinodactyly of the 5th finger, or upper limb reduction defects 1
• Developmental delay: Expected in most cases, with cognitive impairment ≥1.5 SD below the mean 1
• Behavioral issues: Including self-injurious behavior and attention deficits 1

Differential Diagnoses to Exclude

Fetal Alcohol Spectrum Disorder (FASD)

While FASD can present with similar facial features, key distinguishing points include:

• FASD requires short palpebral fissures (≤10th centile), not almond-shaped 1
• FASD features a smooth philtrum (rank 4-5) and thin upper lip 1
• Critical difference: Document prenatal alcohol exposure history; absence makes FASD unlikely 1

Other Genetic Syndromes

• Nijmegen Breakage Syndrome: Features microcephaly and characteristic facies but with more prominent immunodeficiency 1
• ICF Syndrome: Presents with hypertelorism, epicanthal folds, and flat nasal bridge—different facial gestalt 1
• Focal Facial Dermal Dysplasia/Setleis Syndrome: Shows bitemporal scar-like depressions, laterally deficient eyebrows, and prominent upper lip with down-turned mouth 2

Immediate Management Steps

Genetic Testing

• Order NIPBL gene sequencing (accounts for 60% of CdLS cases with autosomal dominant inheritance) 1
• Consider broader genetic panel if NIPBL is negative, as CdLS shows genetic heterogeneity 1

Ophthalmologic Evaluation

• Comprehensive eye examination to assess for:
  • Refractive errors 3
  • Strabismus (esotropia is associated with craniofacial abnormalities) 1
  • Optic nerve hypoplasia (rare but reported in similar genetic conditions) 3
  • Ptosis 1

Neurodevelopmental Assessment

• For children ≥3 years: Formal cognitive testing to document global impairment or specific domain deficits 1
• For children <3 years: Developmental screening to identify delays ≥1.5 SD below the mean 1

Cardiac Evaluation

• Echocardiogram to screen for congenital heart disease (heart murmurs noted in similar conditions) 1

Growth Monitoring

• Plot on appropriate growth curves and monitor for ongoing growth deficiency 1

Common Pitfalls to Avoid

• Do not dismiss the diagnosis based on absence of limb anomalies: CdLS has variable expressivity, and facial features alone can establish the diagnosis 1
• Do not confuse with FASD: The almond-shaped eyes in CdLS differ from the short palpebral fissures in FASD 1
• Do not delay genetic testing: Early diagnosis allows for appropriate surveillance of associated anomalies and genetic counseling 1
• Do not overlook behavioral manifestations: These require specific management strategies and impact quality of life significantly 1

Prognosis and Long-term Considerations

• Most children will have intellectual disability requiring educational support 1
• Increased cancer risk is not a primary feature of CdLS, unlike some other chromosomal repair disorders 1
• Genetic counseling is essential given the autosomal dominant inheritance pattern, though most cases are de novo mutations 1