Figure 1.
Facial dysmorphology rating scale.
Illustrated are a GD 17 fetus having normal facial morphology and 4 fetuses with varying degrees of medial facial deficiency. Numbers assigned to each image (0–4) are scores representing differing degrees of severity of facial dysmorphology. As compared to normal fetuses, those receiving a score of 1 had a notably diminished area of pigmentation between the nostrils (solid arrow) accompanied by reduction in the depth of the normally present median central notch of the upper lip (dashed arrow). A score of 2 was assigned to fetuses that had lost the median lip notch, but still had some remaining pigment at the tip of the nose. Individuals presenting with a single central nostril were assigned a score of 3 and those given a score of 4 had no nostrils.
Figure 2.
Effect of treatment and genotype on facial dysmorphology.
To avoid litter bias, the average dysmorphology score from each genotypic group was determined for each litter in the study population. Values represent the mean plus the standard error of litter averages for each genotype and treatment. Brackets indicate p values of ≤ 0.05 as determined by a one-tailed student’s t-test.
Table 1.
Facial dysmorphology scores by treatment and genotype.
Figure 3.
Subpopulation of GD17 fetuses exhibiting severe craniofacial phenotypes.
Included in the study population were 9 fetuses with phenotypes not typically observed in wildtype C57BL/6J mice exposed to the employed ethanol exposure paradigm (A-I). Single allele mutations in Shh or Gli2 were detected in 8 of 9 fetuses in this severely affected subpopulation. In addition to varying degrees of upper midfacial deficiency, other notable defects included exencephaly (A), iridial coloboma and microphthalmia (A-D), apparent anophthalmia (E, G, I), agnathia (E), micrognathia (A-D, F-I), and proboscis (I). Median cleft lip was also observed (B, C). Within this subpopulation, fetuses were assigned dysmorphology scores as follows: 2 (A), 3 (B-F), 4 (G-I).
Figure 4.
Facial dysmorphology predicts medial forebrain deficiency.
Superior views of dissected brains are shown for a normal fetus (A) and for representative examples of each category of facial dysmorphology (B-E). Medial facial deficiency was associated with increasing hypoplasia of the cerebral cortices (B-E), increasing hypoplasia (B, C) or absence of the olfactory bulbs (D, E), and incomplete division of the forebrain (D, E).