Facial Asymmetry in Nonsyndromic and Muenke Syndrome-Associated Unicoronal Synostosis: A 3-Dimensional Study Based on Facial Surfaces Extracted From CT Scans.

OBJECTIVE: To quantify soft tissue facial asymmetry (FA) in children with nonsyndromic and Muenke syndrome-associated unicoronal synostosis (NS-UCS and MS-UCS), hypothesizing that MS-UCS presents with significantly larger FA than NS-UCS. DESIGN: Retrospective cohort study. PATIENTS AND METHODS: Twenty-one children (mean age: 0.6 years; range: 0.1-1.4 years) were included in the study (NS-UCS = 14; MS-UCS = 7). From presurgical computed tomography scans, facial surfaces were constructed for analysis. A landmark guided atlas was deformed to match each patient's surface, obtaining spatially detailed left-right point correspondence. Facial asymmetry was calculated in each surface point across the face, as the length (mm) of an asymmetry vector, with its Cartesian components providing 3 directions. Mean FA was calculated for the full face, and the forehead, eye, nose, cheek, mouth, and chin regions. RESULTS: For the full face, a significant difference of 2.4 mm (P = .001) was calculated between the 2 groups, predominately in the transverse direction (1.5 mm; P < .001). The forehead and chin regions presented with the largest significant difference, 3.5 mm (P = .002) and 3.2 mm (P < .001), respectively; followed by the eye (2.4 mm; P = .004), cheek (2.2 mm; P = .004), nose (1.7 mm; P = .001), and mouth (1.4 mm; P = .009) regions. The transverse direction presented with the largest significant difference in the forehead, chin, mouth, and nose regions, the sagittal direction in the cheek region, and the vertical direction in the eye region. CONCLUSIONS: Muenke syndrome-associated unicoronal synostosis presented with significantly larger FA in all regions compared to NS-UCS. The largest significant differences were found in the forehead and chin regions, predominantly in the transverse direction.

Phenotypic variability in Muenke syndrome-observations from five Danish families.

Muenke syndrome is a craniosynostosis syndrome associated with the p.Pro250Arg mutation in FGFR3. An increasing number of individuals with this mutation are reported to not have craniosynostosis. The purpose of this report is to increase awareness of the high phenotypic variability seen in Muenke syndrome. DNA testing for the p.Pro250Arg mutation is routinely performed in Denmark, in children presenting with isolated coronal synostosis. Verified diagnosis entails detailed family history, drawing of family pedigree, DNA testing of the parents, genetic counseling, skull radiographs, clinical photographs, and follow-up. Sixteen individuals from 5 Danish families with Muenke syndrome are presented. Large phenotypic variation was seen both within and across families. The most striking observations were that 6/16 (38%) cases did not have craniosynostosis and one individual presented with a normal phenotype. In addition, 3 unrelated cases had incomplete cleft palate, submucous cleft palate, and bifid uvula, respectively. There is strong evidence for reduced penetrance of the craniosynostosis trait in Muenke syndrome. We argue that many studies on Muenke syndrome have been influenced by ascertainment bias in regard to craniosynostosis. In addition, it is suggested that oral clefting might be part of the clinical spectrum seen in Muenke syndrome.

Syringomatous Tumour Presenting as Inversion of a Supernumerary Nipple.

Syringomatous tumour (SyT) is a rare type of benign locally infiltrative tumour with debated origin. Because of the growth pattern, SyT can be mistaken for a malignant tumour, and it is therefore important to keep this diagnosis in mind. This case presents a woman with two supernumerary nipples on each side of the abdomen. One of the nipples was inverted with a small palpable firm mass in close relation to the nipple, leading to referral to the breast surgery department. SyT occurring in a supernumerary nipple and presenting with the symptoms described in this case has to our knowledge never been described previously.

Spatially Detailed 3D Quantification of Improved Facial Symmetry After Surgery in Children With Unicoronal Synostosis.

OBJECTIVE: To assess improvement of soft-tissue facial symmetry in children surgically treated for unicoronal synostosis (UCS) in infancy, to correlate pre- and postsurgical facial asymmetry and to evaluate whether the improvement was visually recognizable. DESIGN: Case-controlled follow-up. PATIENTS/SETTINGS: Eleven Danish children diagnosed with UCS were included, 3 of whom had tested positive for Muenke mutation. Preoperative computed tomography scans and postoperative 3dMD surfaces were available for measurements. A control group of healthy children matched for age and sex was employed. MAIN OUTCOME MEASURES: Pre- and postsurgical facial asymmetry was analyzed using a computerized method capable of objective and spatially detailed quantification in 3-dimension (transverse, vertical, and sagittal directions). Asymmetry was evaluated in the facial region and 6 subregions (forehead, mouth, eyes, nose, cheek, and chin). RESULTS: The largest significant improvement was seen in the sagittal direction of the facial (1.9 mm), forehead (2.0 mm), and cheek (3.4 mm) regions. Small but significant improvements were also seen in the mouth, chin, and eye regions. No significant improvement was seen in the nose region. Significant correlations were found between the pre- and postsurgically calculated facial asymmetry and between calculated asymmetry and clinical validation scores. CONCLUSIONS: All patients presented with improved facial symmetry after surgery and the improvements were visually recognizable. However, only 1 (9.1%) of the 11 patients reached a level of facial asymmetry as low as that seen in the control group. The best outcome was, in general, seen in cases with mild facial asymmetry presurgically.

Facial Asymmetry in Children with Unicoronal Synostosis Who Have Undergone Craniofacial Reconstruction in Infancy.

OBJECTIVE: Quantitatively assess 3D spatially detailed soft-tissue facial asymmetry in children who had undergone craniofacial reconstruction for Unicoronal Synostosis (UCS), and compare the facial asymmetry to control patients. It was hypothesized that there would be no significant differences in the facial asymmetry between the groups. DESIGN: Clinical, retrospective follow-up study. Methodological study. SETTING: Primary care center. PATIENTS/PARTICIPANTS: Twenty-two children with UCS were selected after review of records. INCLUSION CRITERIA: isolated UCS; surgically treated for UCS within the first 19 months of life, without secondary reconstruction; and DNA analysis for the Muenke mutation. An age- and sex-matched control group was employed. INTERVENTIONS: The UCS group had undergone bilateral craniotomy of the frontal bone with unilateral supraorbital rim advancement. MAIN OUTCOME MEASURE(S): Using 3D surface scanning, a detailed map of 3D asymmetry presenting the amount of asymmetry in the sagittal, vertical, and transverse directions was calculated for six facial subregions. RESULTS: The facial asymmetry in the UCS group was significantly larger than in the control group for all regions, to the largest extent in the sagittal direction (level of significance: 5%). The regions with the most pronounced asymmetry were cheeks (mean: 5.45 mm; SD: 1.83 mm), forehead (mean: 5.00 mm; SD: 1.57 mm), and eyes (mean: 4.26 mm; SD: 1.44 mm). CONCLUSIONS: Ninety percent of the UCS patients in the study had significant facial asymmetry throughout the facial area. The study demonstrates a methodology of facial asymmetry quantification well suited for soft-tissue surgical outcome evaluations and long-term follow-up studies in patients with craniofacial anomalies.