Craniosynostosis

A child with an abnormally shaped skull from premature fusion of one or more cranial sutures. Normal sutures stay open into adulthood and accommodate brain growth perpendicular to the suture line; a fused suture forces compensatory growth parallel to it, generating the predictable shape distortions. The bedside task is to identify which suture has fused, decide whether this is single-suture or multi-suture disease, and screen for syndromic features that change the management and recurrence-risk conversation.

Two questions decide the work-up:

1. Which suture(s) fused, and is it single or multiple? Each suture produces a characteristic head shape; multi-suture involvement is much more likely to be syndromic and to threaten intracranial pressure.
2. Syndromic or non-syndromic? Examine hands, feet, face, and growth. Non-syndromic single-suture cases are mostly sporadic and managed surgically; syndromic cases imply an FGFR-pathway disorder or a TWIST1/RAB23 etiology with cascading risks (airway, hearing, vision, midface, cervical spine).

The FGFR trio (FGFR1, FGFR2, FGFR3) accounts for the majority of syndromic craniosynostosis. Limb findings are the fastest distinguishing axis.

FGFR-pathway syndromes

• Apert syndrome (FGFR2, AD; almost all sporadic with paternal-age effect): bicoronal synostosis + midface hypoplasia + syndactyly of digits 2-3-4 fused into a mitten hand (and feet). The syndactyly is the tell. Cleft palate, conductive hearing loss, intellectual disability variable.
• Crouzon syndrome (FGFR2, AD): bicoronal synostosis + exorbitism with midface retrusion + normal hands and feet. Crouzon is "Apert without the syndactyly."
• Pfeiffer syndrome (FGFR1 or FGFR2, AD): synostosis + broad medially deviated thumbs and great toes + variable syndactyly. Type 2 has cloverleaf skull and worst prognosis.
• Muenke syndrome (FGFR3 p.Pro250Arg, AD): often unilateral or bilateral coronal synostosis, variable expressivity (some carriers have no synostosis), sensorineural hearing loss, carpal/tarsal fusions. Specific recurrent variant; targeted testing is high-yield.

Non-FGFR syndromic craniosynostosis

• Saethre-Chotzen syndrome (TWIST1, AD): coronal synostosis + ptosis + low frontal hairline + small ears with prominent crura + cutaneous 2-3 finger syndactyly. Cognition usually normal.
• Carpenter syndrome (RAB23, AR): multi-suture synostosis (often cloverleaf) + postaxial polydactyly + preaxial polysyndactyly of feet + obesity + cardiac defects + ID. The polydactyly distinguishes Carpenter from the FGFR group. (No condition leaf to link.)
• Antley-Bixler syndrome (FGFR2 or POR): synostosis + radiohumeral synostosis + femoral bowing; POR form has disordered steroidogenesis and ambiguous genitalia.

The work-up scales with the number of sutures involved and the presence of syndromic features.

1. Clinical exam and head shape assessment: identify fused suture(s) by palpable ridging, frontal/occipital flattening, and orbital asymmetry; distinguish from positional plagiocephaly (which improves with repositioning and has no ridge).
2. CT head with 3D reconstruction: gold standard to confirm fusion and plan surgery; ultrasound is an alternative in young infants to limit radiation.
3. Ophthalmologic exam: papilledema (raised ICP), exorbitism (Crouzon), exposure keratopathy.
4. Hearing evaluation: conductive loss common in syndromic forms.
5. Polysomnography: obstructive sleep apnea from midface hypoplasia in FGFR syndromes.
6. Targeted gene testing: FGFR2 for Apert/Crouzon/Pfeiffer, FGFR3 p.Pro250Arg for Muenke, TWIST1 for Saethre-Chotzen, RAB23 for Carpenter; craniosynostosis gene panel if pattern unclear.
7. Chromosomal microarray if multiple anomalies suggest a contiguous-gene deletion.
8. Cervical spine imaging before any surgery in FGFR syndromes (C2-C3 fusion in Apert, atlantoaxial instability risks).

Surgical timing is typically before 12 months for non-syndromic single-suture; staged reconstructions in syndromic multi-suture disease.