What causes pediatric craniosynostosis?

Updated: Dec 04, 2018
  • Author: Raj D Sheth, MD; Chief Editor: George I Jallo, MD  more...
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Multiple theories have been proposed for the etiology of primary craniosynostosis, but the most widely accepted is a primary defect in the mesenchymal layer ossification in the cranial bones.

Secondary craniosynostosis typically results from systemic disorders such as the following:

  • Endocrine - Hyperthyroidism, hypophosphatemia, vitamin D deficiency, renal osteodystrophy, hypercalcemia, and rickets

  • Hematologic disorders that cause bone marrow hyperplasia (eg, sickle cell disease, thalassemia)

  • Inadequate brain growth, including microcephaly and its causes and shunted hydrocephalus

The syndromic causes appear to result from genetic mutations in the fibroblast growth factor pathway, particularly genes involving fibroblast growth factor receptors 2 and 3. A gene locus for single suture craniosynostosis has not been identified. [7]

Other important factors to consider include the following:

  • Differentiating plagiocephaly that results from positional molding (which does not require surgery and is seen frequently) from lambdoid suture fusion is extremely important.

  • The presence of multiple suture fusions strongly suggests a craniofacial syndrome, which frequently requires the diagnostic expertise of a pediatric geneticist.

Craniofacial morphogenesis is highly dependent on the patterning information of emigrant cranial neural crest (CNC) cells. CNC cells give rise to a wide variety of tissues and structures, including skull bones. During skull development, cranial sutures serve as growth centers for skeletogenesis that is mediated through intramembranous ossification. This process differs from endochondral ossification in the appendicular and axial skeletons, where prior formation of cartilage templates is required. Axin2 is highly expressed in CNC cells and developing sutures neural crest (nasal and frontal bones) but not mesoderm (parietal bones). Dependent osteogenesis is particularly sensitive to the loss of Axin2. [8]

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