Facial dysmorphism across the fetal alcohol spectrum

Abstract

Objective: Classic facial characteristics of fetal alcohol syndrome (FAS) are shortened palpebral fissures, smooth philtrum, and thin upper vermillion. We aim to help pediatricians detect facial dysmorphism across the fetal alcohol spectrum, especially among nonsyndromal heavily exposed (HE) individuals without classic facial characteristics.

Methods: Of 192 Cape Coloured children recruited, 69 were born to women who reported abstaining from alcohol during pregnancy. According to multifaceted criteria, the remainder were allocated clinically to the FAS (n = 22), partial FAS (n = 26) or nonsyndromal HE (n = 75) categories. We used dense surface modeling and signature analyses of 3-dimensional facial photographs to determine agreement between clinical categorization and classifications induced from face shape alone, to visualize facial differences, and to consider predictive links between face shape and neurobehavior.

Results: Face classification achieved significant agreement with clinical categories for discrimination of nonexposed from FAS alone (face: 0.97-1.00; profile: 0.92) or with the addition of partial FAS (face: 0.90; profile: 0.92). Visualizations of face signatures delineated dysmorphism across the fetal alcohol spectrum and in half of the nonsyndromal HE category face signature graphs detected facial characteristics consistent with prenatal alcohol exposure. This subgroup performed less well on IQ and learning tests than did nonsyndromal subjects without classic facial characteristics.

Conclusions: Heat maps and morphing visualizations of face signatures may help clinicians detect facial dysmorphism across the fetal alcohol spectrum. Face signature graphs show potential for identifying nonsyndromal heavily exposed children who lack the classic facial phenotype but have cognitive impairment.

FIGURE 1

Comparison of facial growth of FASD categories. A, Facial growth indicated by PC1 for FAS and PFAS compared with HCs. B, Facial growth indicated by PC1 for HE compared with HCs. The FAS group show significantly reduced facial growth (P < .001) compared with healthy HCs; the PFAS group are less reduced (P < .001) and the HE group is marginally different (P = .052).

FIGURE 2

Signatures for average faces of clinical categories and for 7 individual children. A, To overcome size difference, average FAS, PFAS, and HE faces were scaled using ratio of nasion to gnathion length before normalization to give signatures reflecting shape only difference ignoring size. Red-green-blue heat maps reflect contraction-coincidence-expansion along surface normal to face at stated significance level. Terms “±1.0 SD,” “±0.6 SD,” and “±0.3 SD” define the upper-lower significance bounds corresponding to the extreme blue-red color range. B, Scaled axial signatures of average FAS face along 3 orthogonal axes. Opposing red-blue coloring proximal to inner and outer canthi of lateral axial signature delineates short palpebral fissures. Blue on nose of vertical axial signature reflects shortening of nose and upward displacement of nasal region. Yellow on nasal bridge and malar regions of depth or anterior-posterior axial signature highlights flattening. Blue on philtrum detects philtral smoothing. Red on chin indicates retrognathia and micrognathia. C, First heat map pair shows raw facial differences for individual with FAS from mean of 35 age-matched controls (green indicates surface coincidence; red/blue ≥5 mm contraction or expansion along surface normal). Second pair is face signature showing how raw differences of reduced face width and proptosis are reversed in relative magnitude. Philtral smoothness is indicated by blue on upper lip. Profile view reveals flat nasal bridge and malar regions, short nose, outward convexity of philtrum, and retrognathia. D, Facial dysmorphism of 6 individuals with HE highlighted by surface profiles (row 2) and heat mapped face signatures at ±2.0 SD (row 1). More illuminating are dynamic morphs between them and age-matched control means (http://www.ucl.ac.uk/~sejjmfj/fasd_morphs.htm) revealing individuals 1 through 4 have mid-facial hypoplasia and philtral smoothing, indivuduals 1, 2, and 6 have retrognathia, and a thin upper lip is suggested in individuals 4 through 6 but not in individuals 1 through 3.

FIGURE 3

Examples of upper lip signatures. Convex philtral grooves are typically delineated by blue regions surrounded by green. When the upper lip is much reduced in size compared with matched controls, convexity may be highlighted as a yellow or green region surrounded by red*. Insert shows region of upper lip modeled.

FIGURE 4

Face signatures of 107 alcohol-exposed individuals, Face signatures at ±2.0 SD of 107 alcohol-exposed individuals with normalization against 35 age-matched healthy controls: FAS (rows 1 and 2), PFAS (rows 3 and 4), and HE (rows 5–9). The term “±2.0 SD” defines the upper-lower significance bounds corresponding to the extreme blue-red color range.

FIGURE 5

Face signature graphs of 107 alcohol-exposed individuals. A, Face signature graph of 18 clusters arising from normalization against controls of 107 children with clinical categorization of FAS, PFAS, or HE. Magnified insets show links between individuals with similar face signatures. B, Color-coded form of signature graph in A. Red/blue/green–filled nodes represent FAS/PFAS/HE individuals, respectively. C, Alternative form of B where FAS and PFAS nodes are red and HE nodes are green. HE individuals in close proximity to FAS/PFAS aggregation are depicted by squares, not circles.