Figure 3.
Morphological Comparison of ALX-Related FNDs
Facial and palate development are illustrated in the upper part of the figure. Regions of the human face that originate from various prominences and palate development in two different stages are shown on the upper left and right, respectively. Palate development occurs between the sixth and seventh week of embryonic development and originates from the median and paired lateral palatine processes (upper right).31 During facial and palate development, the frontonasal prominence contributes to the formation of the bridge of the nose; the lateral processes form the sides of the nose (alae). The merged nasomedial process is crucial to both nasal and palatal development; it forms the intermaxillary segment, which is a precursor of the philtrum of the lip, the pre-maxillary component of the upper jaw, and the primary palate. ALX1 expression is essential not only for building the oral and nasal cavities but also for proper eye development during early embryogenesis. It is not possible to compensate for complete loss of ALX1 function, and frontonasal and palatal development is likely to be disrupted in early stages of development. ALX4 and ALX3 expression are related more to regulating the formation of the final shape of the nose. The ALX4-related FND phenotype is more pronounced than that of ALX3-related FND in terms of the severity of hypertelorism and eye involvement. Alopecia is also associated only with ALX4-related FND. A prominent philtral ridge is characteristic of ALX3-related FNDs (frontorhiny).