Facial Bone Defects Associated with Lateral Facial Clefts Tessier Type 6, 7 and 8 in Syndromic Neurocristopathies: A Detailed Micro-CT Analysis on Historical Museum Specimens

TL;DR

This study uses micro-CT scans of museum specimens to analyze facial bone defects in rare syndromes involving lateral facial clefts, revealing how genetic factors influence bone development.

Contribution

The study provides detailed micro-CT analysis of facial bone defects in three syndromic neurocristopathies, linking morphological changes to specific genetic causes.

Findings

TCS specimen showed absence of zygomatic bones and lateral maxilla.

AFD-Rod specimen exhibited extensive defects in lateral maxilla, zygomatic bones, and mandible.

TETAMS specimen displayed nearly complete absence of jaw formation (agnathia).

Abstract

Lateral facial clefts (Tessier types 6–8) are rare in contrast to the common paramedian cleft lip and palate. They can occur as single malformations but are often part of malformation syndromes and may affect soft tissue structures and underlying bones. Although knowledge of the anatomical changes involved is crucial for understanding disease mechanisms and improving treatment options, detailed morphological analyses of lateral facial clefts are lacking. This study aimed to analyze the facial bone defects in three severely affected fetal museum specimens representing Treacher Collins syndrome (TCS), acrofacial dysostosis syndrome of Rodriguez (AFD-Rod) and tetra-amelia syndrome (TETAMS). Using micro-computer tomography, it was possible to identify distinct alterations in facial bone size, shape, fusions, and disintegration reflecting different gene defects critical in facial development. Possible relationships are discussed between the diverse facial bone defects due to oxidative stress-induced death of neural crest-derived cells, known to be associated with TCS and AFD-Rod, and the more targeted bone defects due to genetic variants known to cause TETAMS. Understanding the morphological manifestations of lateral facial clefts in relation to their genetic background provides valuable insights for both developmental researchers as well as for clinicians diagnosing and classifying congenital clefts and performing surgical reconstructions.

Lateral facial clefts are rare and often part of more complex syndromic neurocristopathies. According to Tessier’s classification, they correspond to facial cleft numbers 6, 7 and 8. Using micro-computer tomography (micro-CT), we analyzed their underlying bone defects (resolution 50 and 55 µm/voxel) in the context of the known syndrome-specific genetic background. Lateral facial clefts were diagnosed in three severely affected museum specimens representing mandibulofacial dysostosis type Treacher Collins syndrome (TCS), acrofacial dysostosis syndrome of Rodriguez (AFD-Rod) and tetra-amelia syndrome (TETAMS). The TCS specimen mainly showed an absence of the zygomatic bones and most of the lateral maxilla. The AFD-Rod specimen showed an extensive defect of the lateral maxilla, zygomatic bones, and mandible. The TETAMS specimen showed almost isolated agnathia. Possible relationships are discussed between the diverse facial bone defects due to apoptosis of neural crest-derived cells, known to be associated with ribosomopathies and spliceosomopathies, such as TCS and AFD-Rod, and the more targeted bone defects due to genetic variants known to cause TETAMS.

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