Etiological heterogeneity and clinical characteristics of metopic synostosis: Evidence from a tertiary craniofacial unit

Am J Med Genet A. 2010 Jun;152A(6):1383-9. doi: 10.1002/ajmg.a.33435.


Metopic synostosis (MS) accounts for approximately 10-15% of all craniosynostosis and is etiologically heterogeneous. This study aimed to examine the causes of MS, as observed in a tertiary craniofacial unit. We reviewed the case notes of 110 children with a diagnosis of MS, attending the craniofacial unit in Oxford between 1991 and 2008. Our results showed 38 children (38/110 or 34.6%) who had at least one additional structural abnormality or had a known syndromic diagnosis were classed as having syndromic MS. Chromosomal abnormalities were noted in 8/38 (21.4%) children: mosaic marker chromosome 2, 9p deletion (2/8), 11q deletion, 12pter deletion and duplication of 15q25 with other additional chromosomal abnormalities (3/8). Other syndromic diagnoses included Silver-Russell syndrome and Greig cephalopolysyndactyly. Prenatal exposure to sodium valproate (VPA) was noted in 8/110 children (7.8%), with the dose of the VPA being >or=1,000 mg/day in all cases. Other prenatal exposures reported in this study were: maternal diabetes (6/110), enoxaparin for hypercoagulable state (1/110), and thyroxine (1/110). The majority of patients (72/110 or 65.4%) had nonsyndromic MS. Speech delay was present in 11 children with nonsyndromic MS (11/72 or 15.3%) and 10 children with syndromic MS (10/38 or 26.3%). We conclude that approximately two-thirds of all MS is nonsyndromic. Prenatal exposure to VPA is a common cause of MS. Maternal diabetes, not previously linked to MS, was noted in 5.5% of cases. Chromosomal abnormalities account for about 6% of MS. An increased risk of speech delay is seen with both the syndromic and nonsyndromic forms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anticoagulants / adverse effects
  • Child
  • Child, Preschool
  • Chromosome Aberrations
  • Craniosynostoses / chemically induced
  • Craniosynostoses / etiology*
  • Craniosynostoses / genetics
  • Enoxaparin / adverse effects
  • Female
  • Humans
  • Male
  • Pregnancy
  • Pregnancy in Diabetics
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / diagnosis
  • Prenatal Exposure Delayed Effects / genetics
  • Thyroxine / adverse effects
  • Valproic Acid / adverse effects
  • Young Adult


  • Anticoagulants
  • Enoxaparin
  • Valproic Acid
  • Thyroxine