Recent advances in trigonocephaly

Abstract

Introduction. The aim of this review was to report on recent advances in trigonocephaly since the last report on craniosynostosis published in 2006. Material and methods. The review was conducted in accordance with the PRISMA guidelines. Research focused on four main topics: epidemiology, neurodevelopmental disorders, genetics and surgical techniques. Results. Forty reports were included. The prevalence of trigonocephaly increased during the last two decades both in Europe and in the United States, but no clear contributing factors have yet been identified. Neurodevelopmental disorders are frequent in syndromic trigonocephaly and not particularly rare in non-syndromic cases (up to 34%). Developmental retardation (speech, motor or global) was almost always present in children exposed to valproic acid. Chromosomal abnormalities described in metopic synostosis comprised deletion of chromosome 11q24, deletion or trisomy of 9p and deletion of 7p, deletions of 3q, 13q, 12pter, 22q11, and duplication of 15q25. SMAD6 mutations should be systematically screened for in familial cases. Recent advances in surgical techniques have mainly concerned endoscopic-assisted procedures, as they significantly reduce perioperative morbidity. Conclusions. Neurosurgeons, maxillofacial and plastic surgeons will be increasingly concerned with trigonocephaly because of the increase in prevalence observed over the last two decades. Cytogenetic alterations are probably underestimated in this craniosynostosis, considering the high rate of neurodevelopmental retardation compared to other single-suture synostoses. Genetic counseling is therefore more and more effective in this pathology. An objective method to evaluate the cosmetic results of both endoscopic and open surgeries is necessary, as some under-corrections have been reported with minimally invasive surgery.

Trigonocephaly and Cranium Bifidum Occultum Treated Simultaneously Using the Split-Bone Technique and Piezosurgery

“…Nonetheless, in the present case report, no familial inheritance was observed and no mutations were identified. Moreover, the patient had no characteristic facial dysmorphisms or psychomotor retardation, as reported in almost 6% of trigonocephalic patients with specific mutations [ 13 ].…”

“…Its etiology has been attributed to an abnormality in intramembranous ossification during the fifth month of gestation, and several gene mutations have been described that make this condition hereditary in nature, such as loss of function mutations in human homeobox genes MSX2 in chromosome 5 and ALX4 in chromosome 11 [ 3 , 5 , 11 , 12 ]. Interestingly, a deletion in chromosome 11q24 and a mutation in ALX4 are two of the mutations described in association with syndromic trigonocephaly, and an increasing incidence of this craniosynostosis has been reported over the last two decades [ 8 , 9 , 13 ]. Folic acid intake is also considered to be a risk factor that explains some of the increased incidences of trigonocephalic cases, and this factor has the potential to explain the genesis of cranium bifidum [ 13 ].…”

“…Interestingly, a deletion in chromosome 11q24 and a mutation in ALX4 are two of the mutations described in association with syndromic trigonocephaly, and an increasing incidence of this craniosynostosis has been reported over the last two decades [ 8 , 9 , 13 ]. Folic acid intake is also considered to be a risk factor that explains some of the increased incidences of trigonocephalic cases, and this factor has the potential to explain the genesis of cranium bifidum [ 13 ]. Therefore, epigenetic and environmental factors could also play a role in the development of metopic synostosis and CBO.…”

“…Furthermore, even in non-syndromic craniosynostosis cases, mutations in specific genes, such as Transcription Factor 12 (TCF12), Ephrin B1 (EFBN1), Cytochrome P450 Oxidoreductase (POR), Fibroblast Growth Factor 10 (FGF10), FRAS1 Related Extracellular Matrix 1 (FREM1), and Smad Family Member 6 (SMAD6) have been identified, specifically in trigonocephaly [ 13 ]. Nonetheless, in the present case report, no familial inheritance was observed and no mutations were identified.…”

Craniometric Measurements and Surgical Outcomes in Trigonocephaly Patients Who Underwent Surgical Treatment

“…The incidence of TC was previously estimated to range from 1/10,000 to 1/15,000 births on average. Recently, the incidence of TC has increased (1/5,000) due to an unknown cause and has become the second most common isolated single suture synostosis in series [2,3,11]. Di Rocco et al have stated that there was a 420% increase in TC in the 20 years before 2009 [1].…”