Craniofrontonasal syndrome

Craniofrontonasal syndrome (CFNS) is a rare X-linked dominant disorder characterized by a more severe phenotype of multiple skeletal malformations in heterozygous females in contrast to no or mild clinical features in hemizygous males. Females typically display craniofacial asymmetry, marked hypertelorism with a central nasal groove, bifid nasal tip, coronal craniosynostosis (unilateral or bilateral), corpus callosum agenesis, thick wiry hair, and occasionally cleft lip and/or palate. Extracranial features include sloping shoulders with dysplastic clavicles, asymmetry of the thoracic skeleton and pectoral muscle, unilateral breast hypoplasia, longitudinally grooved fingernails, mild cutaneous syndactyly, and umbilical and diaphragmatic hernia. Hemizygous males have no or only mild manifestations such as hypertelorism and less frequently cleft lip and/or palate.

Tests Available

Forms and Documents

Test Details

  • Confirmation of a clinical diagnosis
  • Risk assessment
  • Prenatal diagnosis in families with a known mutation
  • Capillary Sequencing


3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs


  • 756 Other congenital musculoskeletal anomalies Excludes: congenital myotonic chondrodystrophy (359.23) those deformities classifiable to 754.0-754.8
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  1. Wieland, I. et al. Mutations of the Ephrin-B1 Gene Cause Craniofrontonasal Syndrome. Am J Hum Genet. 74:1209-1215, 2004.
  2. Twigg, S. et al. Mutations of ephrin-B1 (EFNB1), a marker of tissue boundary formation, cause craniofrontonasal syndrome. PNAS. 101:8652-8657, 2004.
  3. Wieland, I. et al. Dissecting the molecular mechanism in craniofrontonasal syndrome: differential mRNA expression of mutant EFBN1 and the cellular mosaic. Eur J Hum Genet. 16: 184-191, 2008.
  4. Twigg, S. et al. The Origin of EFNB1 Mutations in Craniofrontonasal Syndrome: Frequent Somatic Mosaicism and Explanation of the Paucity of Carrier Males. Am J Hum Genet. 78:999- 1010, 2006.
  5. Wieland, I. et al. Twenty-Six Novel EFNB1 Mutations in Familial and Sporadic Craniofrontonasal Syndrome (CFNS) Hum. Mutat. 26:113-118, 2005.
  6. Wieland, I. et al. Contiguous gene deletions involving EFNB1, OPHN1, PJA1 and EDA in patients with craniofrontonasal syndrome. Clin Genet. 72:506-516, 2007.