Measurement of inferior facial angle and prefrontal space ratio in first trimester fetuses with aneuploidies: a retrospective study.

Objective To determine whether the measurement of inferior facial angle (IFA) and prefrontal space ratio (PFSR) in two-dimensional (2D) ultrasound images in the first trimester of pregnancy is reliable and to describe these markers in normal and aneuploid fetuses. Methods IFA and PFSR were measured in stored 2D midsagittal images of 200 normal and 140 aneuploid fetal profiles between 11 + 0 and 13 + 6 weeks of gestation. Limits of agreement (LOAs) and intraclass correlation coefficients (ICCs) for inter- and intraobserver differences were calculated. Results The mean IFA in normal fetuses was 76.5° ± 6.3. Between the two measurement rounds of the same observer, the LOAs were -5.4 to 7.1 (obs. 1) and 7.4 to 8.4 (obs. 2). For IFA measurements by the same observer the ICC was 0.88 (obs. 1) and for measurements by two different observers the ICC was 0.74. The mean PFSR was 0.76 ± 0.40 and the intraobserver LOAs were -0.372 to 0.395 (obs. 1) and -0.555 to 0.667 (obs. 2). For PFSR measurements by the same observer the ICC was 0.89 (obs. 1) and for measurements by two different observers the ICC was 0.65. Among aneuploid fetuses, IFA was below the normal range in one third of the cases with trisomy 18. PFSR was below the 95% prediction limit in 16.2% of fetuses with trisomy 21% and 17.9% of fetuses with trisomy 18. Conclusion IFA can be reliably measured in 2D ultrasound images in the first trimester of pregnancy with a high interobserver agreement and may provide information about retrognathia associated with various syndromes and aneuploidies at early stages of pregnancy.

Prenatal indices for mandibular retrognathia/micrognathia.

OBJECTIVE: Micro- and retrognathia of mandibular origin may lead to life-threatening respiratory problems in connection with glossoptosis immediately after birth. Prenatal screening for this malformation is therefore increasingly important. Today this is accomplished by predominantly subjective standards. Objective criteria have been proposed but have not become established. We therefore made an effort to develop indices that would identify major skeletal discrepancies or micrognathia in as straightforward a fashion as possible during routine prenatal sonography. MATERIALS AND METHODS: Series of fetal jaw sonograms (Toshiba Aplio MX®) were obtained in 313 women with normal pregnancies from weeks 19-29 of gestation. Upper- and lower-jaw landmarks were interactively located on screen and evaluated for reproducibility. Linear parameters representative of maxillary and mandibular length (SpA'-SpP' and Rami-SymMe) were measured and related to femur length and gestational age. Based on these data, indices for maxillary, and mandibular length were derived and analyzed. RESULTS: High correlations were identified for mandibular length both with gestational age (R = 0.845; R(2) = 0.713) and with femur length (correlation coefficients (R) = 0.839; coefficients of determination (R(2)) = 0.704). For maxillary length, the respective correlation coefficients were 0.691 (R(2) = 0.477) and 0.656 (R(2) = 0.430). Estimates of mandibular and maxillary length based on gestational age and femur length were obtained by regression analysis. The mean bimaxillary length ratio was 0.628 ± 0.043. CONCLUSION: Maxillary and mandibular growth can be objectively evaluated via indices. It is conceivable to develop this approach into a sensitive and reliable method of prenatal jaw screening for major skeletal anomalies and congenital malformations.

Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis.

MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th pharyngeal arch artery (PAA) remodeling was affected, resulting in interrupted aortic arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and pharyngeal arch artery morphogenesis.

Experimental aspects of the pathogenesis of Robin sequence.

OBJECTIVE: The Pierre Robin Sequence (PRS) is a good example of disturbed embryonic development of the secondary palate involving insufficient mandibular growth, failed forward tongue movement, and, in the case of a cleft, impeded fusion of the secondary palate. Discussion continues regarding which of the involved pathogenetic factors is the primary cause of the induced cascade of signs: insufficient mandibular growth or failed descent of the tongue. DESIGN: Forty-five randomly selected, 18-day-old formalin-fixed A/WySn mouse fetuses were investigated. The strain is known to have a basic genetic defect and as much as 44% clefts in the offspring. Twenty-four fetuses in the group had a cleft palate. Mandible position was measured relative to the head and to the presence or absence of a cleft. Cleft width and tongue position were also determined. Thirty-eight NMRI mouse fetuses of the same age served as controls. RESULTS: All A/WySn fetuses showed marked mandibular retrognathia, which was more severe in the cleft group (p < .05), but there was no correlation between the degree of retrognathia and cleft width. The median cleft width was 3.4 mm (1.6 through 6.3 mm). The tongue was in the cleft in all 12 fetuses with wide clefts (>3.4 mm wide), and free in the oral cavity in the other 12. Tongue position did not influence the degree of retrognathia (p < .05). Moreover, the tongue was free in all fetuses with severe retrognathia. CONCLUSION: The results support the primary role of retroposition of the mandible in the development of cardinal symptoms of Pierre Robin Sequence.

Morphological deficiency in the prenatal anterior cranial base of midfacially retrognathic mice.

The role of the anterior cranial base in the establishment of midfacial retrognathia remains unclear. The purpose of this study was to determine whether morphological deficiencies occur in the developing anterior cranial base of the retrognathic Brachyrrhine (3H1 Br/+) mouse mutant shortly after overt cartilaginous differentiation and to localise any malformations. Crania from 2 groups of 3H1 Br/+ and +/+ mice, each consisting of 15 animals, were collected at gestational days 15, 17, and 19 (Theiler stages 23, 25, 27). The anterior cranial base from each specimen was subjected to computerised reconstruction and 8 homologous anatomical landmarks were digitised on each model. The landmark configurations were subjected to Procrustes analysis and significant differences between models were determined at each age. In order to localise differences between forms, average landmark configurations derived from Procrustes analysis were subjected to finite-element analysis. Two cluster models were generated based on size-change values. One cluster was located anteriorly and superiorly while the second was located posteriorly and inferiorly within the anterior cranial base. Results indicate that the size-change values for the posterior and inferior cluster increased more rapidly compared with the anterior and superior region over the age range tested. These data indicate that the midfacial retrognathia in Br/+ mice is associated with abnormal growth activity in the presphenoid component of the presumptive anterior cranial base. In addition, the deficiency is present in the presphenoid at the time of overt cartilaginous differentiation.

Mandibular growth rates in human fetal development.

A morphometric analysis of changing proportions in the developing mandible was undertaken in 18 human embryos and fetuses of both sexes (developmental age from 8 to 14 weeks, crown-rump length, CRL, from 34 to 110 mm), previously cleared and stained with a specific method for bone (alizarin red S). Reference points were located on the mandible, i.e. condylar process (Pcl), coronoid process (Pco), gnathion (GN), gonion (GO), superior symphyseal point (SSP), for measuring linear dimensions, i.e. Pcl-GN, Pcl-Pco, Pco-GN, GO-GN, SSP-GN. The gonial (Pcl-GO-GN) and the (Pcl-GN-Pcl) angles were also measured. All linear dimensions were correlated with the CRL by bivariate allometry (1n y = 1n a+b 1n x): they all grew with positive allometry, except GO-GN with isometry. The mandibular ramus grew relatively faster than the body, both in length and height, and the greatest growth rate was found for ramus height. The relation between mandibular shape and the craniofacial structures was investigated using scale drawings obtained from photographs of fetal skulls in lateral view. In the youngest fetuses the mandible was prognathic, then became retrognathic. During the period investigated the zygomatic process and squama of the temporal bone were in a lower and more inclined position in relation to the transverse plane passing through the zygomatic arch than in the newborn and adult. This study identifies parameters fitting changing trends in height, length and shape of the human mandible during the prenatal period (8-14 weeks); moreover, it emphasizes that the mandibular growth patterns differ significantly from those of successive development periods.