What are the key differentials to consider when diagnosing and managing craniosynostosis in pediatric patients, particularly infants and toddlers?

Differential Diagnosis of Craniosynostosis

The primary differential for craniosynostosis is positional plagiocephaly (deformational skull flattening), which can be distinguished clinically in the vast majority of cases without imaging. 1, 2

Key Clinical Differentials

Positional Plagiocephaly (Most Common Differential)

• Positional plagiocephaly presents with bilateral occipital flattening that improves with repositioning efforts, distinguishing it from true craniosynostosis 1
• Clinical examination alone is sufficient to differentiate these conditions in the vast majority of cases, with imaging reserved only for equivocal findings 1, 2
• Key distinguishing features include parallelogram-shaped head deformity without palpable ridges along suture lines, and improvement with repositioning 1

Benign Metopic Ridge

• A palpable midline metopic ridge can occur as a normal variant without true craniosynostosis 3
• True metopic craniosynostosis presents with characteristic triangular forehead, bitemporal narrowing, and hypotelorism (closely-spaced eyes), not just an isolated ridge 3
• Clinical examination focusing on forehead shape and orbital spacing differentiates benign ridge from pathologic synostosis 3

Secondary Causes to Consider

Metabolic and Hematologic Disorders

• Secondary craniosynostosis from metabolic or hematologic disorders affecting bone metabolism typically presents much later than primary congenital forms 4
• These conditions should be considered when craniosynostosis presents outside the typical neonatal/early infancy period 4

Syndromic Craniosynostosis (Critical Not to Miss)

• Syndromic forms (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen syndromes) involve multisuture synostosis with associated dysmorphisms and require referral to nationally designated craniofacial centers 1, 3, 4
• Look for facial dysmorphisms, limb abnormalities, developmental delays, and involvement of multiple sutures 4, 5
• Genetic mutations in FGFR1, FGFR2, FGFR3, TWIST, and MSX2 genes have been identified in these syndromes 5, 6

X-Linked Hypophosphatemia (XLH)

• Craniosynostosis is a recognized neurosurgical complication of XLH, along with Chiari malformations and syringomyelia 7
• Consider XLH when craniosynostosis occurs with rickets, bone pain, growth failure, or leg bowing 7

Diagnostic Approach to Differentiation

Clinical Examination (First-Line)

• Head circumference measurements tracked serially - insufficient increase may indicate craniosynostosis 2, 3
• Palpation for ridged, fused sutures - present in craniosynostosis, absent in positional plagiocephaly 1, 3
• Fundoscopic examination for papilledema indicating increased intracranial pressure 1, 3
• Neurological assessment for developmental delays and signs of elevated intracranial pressure 1, 3

Imaging Strategy (When Clinical Examination is Equivocal)

• Ultrasound is the first-line imaging modality for suspected cranial suture anomalies when clinical examination cannot definitively exclude craniosynostosis 1, 2
• Skull X-rays can serve as an alternative first-line imaging option 1
• CT scanning should be avoided routinely due to radiation risks and reserved only for surgical planning in confirmed cases or when ultrasound/X-rays are non-diagnostic 1, 2
• MRI has no role in diagnosing craniosynostosis itself but is indicated for evaluating associated intracranial complications like Chiari malformation 1

Critical Pitfalls to Avoid

• Do not routinely order imaging for fontanelle abnormalities - diagnosis is primarily clinical 2
• Do not miss syndromic craniosynostosis by failing to examine for associated dysmorphic features and developmental delays 1, 3
• Do not delay referral to pediatric neurosurgery when craniosynostosis is confirmed clinically or when signs of increased intracranial pressure are present 1
• Remember that even "benign" forms of non-syndromic craniosynostosis can result in subtle cognitive and behavioral impacts, requiring long-term follow-up 8