Metopic Craniosynostosis

GENESIS

The range of incidence of metopic synostosis occurs in about 0.67–14 per 10,000 births. It accounts for 10–20% of patients requiring calvarial surgery, making it the third most common type of craniosynostosis in the clinic. It is characterized by trigonocephaly, lateral supraorbital retrusion, and hypotelorism. Like sagittal synostosis, metopic synostosis occurs more frequently in males, with a 2–6.5:1 male:female ratio reported with no maternal or paternal age effect. Only 5.6% of cases have been familial. The frequency of associated twinning was 7.8% of 179 pedigrees studied, with two twin monozygotic pairs concordant. The similarity of epidemiologic features in sagittal and metopic craniosynostosis suggests that prenatal lateral constraint of the frontal part of the head is a frequent cause of metopic craniosynostosis ( Figs. 32.1–32.4 ). Examples of constraint-induced metopic synostosis have included a monozygotic triplet whose forehead was wedged between the buttocks of her two co-triplets in utero (see Fig. 32.3 ) and an infant whose head was compressed within one horn of his mother’s bicornuate uterus (see Fig. 32.4 ). There is also some evidence to suggest that fetal head constraint can induce chondrocyte apoptosis and alter the expression of transforming growth factor beta and fibroblast growth factor receptors, resulting in nonsyndromic craniosynostosis.

The metopic suture is the first cranial suture to close, and analysis of computed tomography scans in patients with and without metopic synostosis demonstrated that the metopic suture normally begins to close at 3 to 4 months and is usually completely closed by 8 to 9 months. Fusion can be normal and completed as early as 2 months, and can also stay patent and persist into adulthood. Normal fusion commences at the nasion and proceeds superiorly, concluding at the anterior fontanelle.

Trigonocephaly is usually an isolated anomaly in an otherwise normal child, but it can occur as part of a syndrome in about 35% of cases. Examples include Baller-Gerold, Saethre-Chotzen, Say-Mayer, and Opitz C trigonocephaly syndrome ( Fig. 32.5 ), or result from a wide range of chromosome abnormalities, such as deletions of 9p22-p24 or 11q23-q24, the latter deletion also called Jacobsen syndrome ( Fig. 32.6 ). In a study of 25 infants with trigonocephaly and metopic synostosis, 6% were familial, 16 (64%) had isolated metopic synostosis, two (8%) had metopic synostosis combined with sagittal synostosis, and seven (28%) had metopic synostosis as part of a syndrome (two with Jacobsen syndrome due to chromosomal deletion of 11q23-q24, one with Opitz C trigonocephaly syndrome, one with Say-Meyer trigonocephaly syndrome, one with I-cell disease, and two others with unknown syndromes). In a study of 76 unrelated patients with syndromic (36 patients) and nonsyndromic trigonocephaly (40 patients) caused by metopic synostosis, molecular screening for microdeletions at 9p22-p24 and 11q23-q24 revealed deletions in seven syndromic patients (19.4%), but no deletions were found in the nonsyndromic patients. The ratio of affected males to females was 5:1 in the syndromic group and 1.8:1 in the nonsyndromic group, which suggests that genes in these deleted regions and on the X-chromosome play a major role in syndromic trigonocephaly.

In another study of 278 cases of metopic synostosis, 75% were nonsyndromic and 6% were familial. Metopic synostosis has also been associated with fetal exposure to valproic acid but not with exposure to other anticonvulsants. The mean intelligence quotient of 17 patients with metopic synostosis was 75; significantly higher intelligence quotients were noted in infants who were surgically treated before 6 months of age.