OBJECTIVE: To prospectively evaluate the prognosis of fetuses diagnosed with micrognathia using prenatal ultrasound screening.
METHODS: Between January 2019 and December 2022, a normal range of IFA to evaluate the facial profile in fetuses with micrognathia in a Chinese population between 11 and 20 gestational weeks was established, and the pregnancy outcomes of fetal micrognathia were described. The medical records of these pregnancies were collected, including family history, maternal demographics, sonographic findings, genetic testing results, and pregnancy outcomes.
RESULTS: Ultrasound identified 25 patients with fetal micrognathia, with a mean IFA value of 43.6°. All cases of isolated fetal micrognathia in the initial scans were non-isolated in the following scans. A total of 78.9% (15/19) cases had a genetic cause confirmed, including 12 with chromosomal abnormalities and 3 with monogenic disorders. Monogenic disorders were all known causes of micrognathia, including two cases of campomelic dysplasia affected by SOX9 mutations and one case of mandibulofacial dysostosis with an EFTUD2 mutation. In the end, 19 cases were terminated, 1 live birth was diagnosed as Pierre Robin syndrome, and 5 cases were lost to follow-up.
CONCLUSIONS: IFA is a useful indicator and three-dimensional ultrasound is a significant support technique for fetal micrognathia prenatal diagnosis. Repeat ultrasound monitoring and genetic testing are crucial, with CMA recommended and Whole exome sequencing performed when normal arrays are reported. Isolated fetal micrognathia may be an early manifestation of monogenic disorders.

Objective:To explore the perioperative airway management and treatment of newborns with micrognathia and laryngomalacia. Methods:From January to December 2022, a total of 6 newborns with micrognathia and laryngomalacia were included. Preoperative laryngoscopy revealed concomitant laryngomalacia. These micrognathia were diagnosed as Pierre Robin sequences. All patients had grade Ⅱ or higher symptoms of laryngeal obstruction and required oxygen therapy or non-invasive ventilatory support. All patients underwent simultaneous laryngomalacia surgery and mandibular distraction osteogenesis. The shortened aryepiglottic folds were ablated using a low-temperature plasma radiofrequency during the operation. Tracheal intubation was maintained for 3-5 days postoperatively. Polysomnography（PSG） and airway CT examination were performed before and 3 months after the surgery. Results:Among the 6 patients, 4 required oxygen therapy preoperatively and 2 required non-invasiveventilatory support. The mean age of patients was 40 days at surgery. The inferior alveolar nerve bundle was not damaged during the operation, and there were no signs of mandibular branch injury such as facial asymmetry after the surgery. Laryngomalacia presented as mixed type: type Ⅱ+ type Ⅲ. The maximum mandibular distraction distance was 20 mm, the minimum was 12 mm, and the mean was 16 mm. The posterior airway space increased from a preoperative average of 3.5 mm to a postoperative average of 9.5 mm. The AHI decreased from a mean of 5.65 to 0.85, and the lowest oxygen saturation increased from a mean of 78% to 95%. All patients were successfully extubated after the surgery, and symptoms of laryngeal obstruction such as hypoxia and feeding difficulties disappeared. Conclusion:Newborns with micrognathia and laryngomalacia have multi-planar airway obstruction. Simultaneous laryngomalacia surgery and mandibular distraction osteogenesis are safe and feasible, and can effectively alleviate symptoms of laryngeal obstruction such as hypoxia and feeding difficulties, while significantly improving the appearance of micrognathia.
目的：探讨小下颌畸形伴喉软化新生儿的围手术期气道管理及治疗。 方法：2022年1—12月共纳入6例小下颌畸形伴喉软化新生儿。术前喉镜检查发现合并喉软化。小下颌畸形确诊为皮罗综合征。术前患儿均存在Ⅱ度以上的喉梗阻表现，需予以吸氧或无创呼吸机辅助通气治疗。所有患儿均同期行喉软化手术和双侧下颌骨牵引成骨术，术中用低温等离子射频刀消融短缩的杓会厌皱襞，术后气管插管3～5 d。术前、术后3个月行多导睡眠呼吸监测评估（PSG）及气道CT检查。 结果：6例患儿中4例术前需要吸氧，2例需无创呼吸机辅助通气治疗。手术平均年龄为40 d，术中均未损伤下牙槽神经血管束，术后均未出现口角歪斜等下颌缘支损伤表现。喉软化表现为混合型：Ⅱ型+Ⅲ型；最大下颌骨牵引延长距离20 mm，最小12 mm，平均16 mm；后气道间隙由术前平均3.5 mm增加到术后9.5 mm；AHI由平均5.65降至0.85，最低血氧饱和度由平均78%增加至95%。术后患儿均成功拔除气管插管，缺氧、喂养困难等喉梗阻症状均消失。 结论：小下颌畸形伴喉软化新生儿存在多平面的气道梗阻，早期同时行喉软化术和下颌骨牵引成骨术安全可行，能有效解决患儿缺氧、喂养困难等喉梗阻症状，同时显著改善小下颌的外观。.

UNASSIGNED: This systematic review aimed to analyze the characteristics of different diagnostic techniques for micrognathia, summarize the consistent diagnostic criteria of each technique, and provide a simple and convenient prenatal diagnosis strategy for micrognathia.
UNASSIGNED: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the search was undertaken in three international databases (PubMed, Scopus, and Web of Science). The three reviewers assessed all papers and extracted the following variables: author\'s name and year of publication, country, study design, number of participants, gestational age, equipment for prenatal examination, biometric parameters related to micrognathia, main results.
UNASSIGNED: A total of 25 articles included in the analysis. Nineteen articles described cross-sectional studies (76 percent), 4 (16 percent) were case-control studies, and 2 (8 percent) were cohort studies. Fifteen studies (60 percent) had a prospective design, 9 (36 percent) had a retrospective design, and one (4 percent) had both prospective and retrospective design. Thirty-two percent of the studies (n = 8) were performed in USA, and the remaining studies were performed in China (n = 4), Israel (n = 3), Netherlands (n = 3), UK (n = 1), France (n = 1), Italy (n = 1), Belgium(n = 1), Germany (n = 1), Spain (n = 1), and Austria (n = 1). The prenatal diagnosis of micrognathia can be performed as early as possible in the first trimester, while the second and third trimester of pregnancy were the main prenatal diagnosis period. The articles that were included in the qualitative synthesis describe 30 biometric parameters related to the mandible.
UNASSIGNED: Of the 30 biometric parameters related to the mandible, 15 can obtain the simple and convenient diagnostic criteria or warning value for micrognathia. Based on these diagnostic criteria or warning value, clinicians can quickly make a preliminary judgment on facial deformities, to carry out cytologic examination to further clarify the diagnosis of micrognathia.

Lethal multiple pterygium syndrome (LMPS) is a rare disease with genetic and phenotypic heterogeneity and is inherited in an autosomal recessive (AR) pattern. Here, we have presented clinically significant results describing two novel mutations of CHRND gene: NM_000751.2: c.1006C>T p.(Arg336Ter) and NM_000751.2:c.973_975delGTG p.(Val325del), and measurement of the facial angle for determining micrognathia by prenatal diagnosis in the first trimester of pregnancy for a Lethal multiple pterygium syndrome case. In conclusion, this report complements the spectrum of genetic variants and phenotype of Lethal multiple pterygium syndrome and provides reliable recommendation for the counseling of future pregnancies in families with the disease.

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OBJECTIVE: To establish reference ranges for fetal mandibular markers in low-risk singleton pregnancies between 11 and 13 + 6 weeks of gestation in a Chinese population.
METHODS: The inferior facial angle (IFA), transverse, and anteroposterior diameters of the mandible, and mandibular length were measured at 11-13 + 6 weeks of gestation. The utility of these sonographic markers for detecting micrognathia was explored in seven fetuses.
RESULTS: In healthy fetuses at 11-13 + 6 weeks, there were linear correlations between gestational age and the transverse (Y = -15.615 + 1.987X, r = 0.718, p < 0.001) and anteroposterior (Y = -8.557 + 1.101X, r = 0.581, p < 0.001) diameters of the mandible; mean ratio of the anteroposterior: transverse diameters of the mandible decreased with gestational age (Y = 0.603-0.003X, r = 0.018, p = 0.755); there was a positive correlation between crown rump length and mandibular length (mandible length = 0.861 + 0.137*crown rump length; r = 0.723, p < 0.001); and there was a positive correlation between crown rump length and IFA (r = 0.234, p < 0.05). Reference ranges were: mean ratio of anteroposterior diameter: transverse diameter of the mandible 0.56; mean mandibular length 9.05 mm; and median IFA 66.5°. The values for these mandibular markers in seven cases of fetal micrognathia were outside the normal range.
CONCLUSIONS: Evaluations of fetal mandibular markers during first trimester ultrasound screening may contribute to the early detection and diagnosis of micrognathia. We recommend obtaining a subjective impression of the mandible on the mid-sagittal view routinely used to measured nuchal translucency, followed by targeted objective measurements on the mid-sagittal and axial views in suspected cases.

OBJECTIVE: To evaluate the prognosis of fetuses with a prenatal diagnosis of micrognathia in the first trimester.
METHODS: Over a 3-year period, patients with fetal micrognathia were detected at the time of nuchal translucency screening. The medical records of these pregnancies were reviewed, including maternal demographics, sonographic findings, genetic testing results and pregnancy outcomes.
RESULTS: Forty-three cases of first-trimester micrognathia were included in this study. Chromosomal abnormalities were detected in seven cases. Of the fetuses with a normal array, further investigation of monogenic disorders with whole-exome sequencing was undertaken in 13 cases. Monogenic syndromes were identified in eight cases, including six with de-novo dominant alleles and two with recessive conditions. Whole-exome sequencing was refused in 23 cases; among these, other additional anomalies were found on anatomic ultrasound in 10 cases.
CONCLUSIONS: This study demonstrated that caution should be adopted when finding an apparently isolated micrognathia in early gestation, even with a normal array. A diagnosis of genetic syndrome or multiple anomalies on subsequent scans is most likely, and will affect the final prognosis.

BACKGROUND: The highly conserved Grainyhead-like (Grhl) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead-like 2 (Grhl2) leads to mid-gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning.
RESULTS: Here, using four separate Cre-lox conditional deletion models, as well as one genetic epistasis approach (Grhl2+/- ;Edn1+/- double heterozygous mice) we have investigated tissue-specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the ShhCre driver) leads to low-penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx (NestinCre ) leads to small, albeit significant, differences in the proximal-distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm (Sox17-2aiCre ) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm-derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest (Wnt1Cre ) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1.
CONCLUSIONS: Taken together, our study identifies a pharyngeal-epithelium intrinsic, non-cell-autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm-specific role for Grhl2 in the formation and establishment of the mammalian lung.

OBJECTIVE: We present prenatal diagnosis of a de novo 1.651-Mb 19q13.42-q13.43 microdeletion in a fetus with micrognathia and bilateral pyelectasis on prenatal ultrasound.
METHODS: A 32-year-old woman underwent amniocentesis at 28 weeks of gestation because of fetal micrognathia and bilateral pyelectasis on prenatal ultrasound. Amniocentesis revealed a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 19q13.42q13.43 (55,028,722-56,680,564) × 1.0 [GRCh37 (hg19)] or a 1.651-Mb microdeletion encompassing 44 Online Mendelian Inheritance in Man (OMIM) genes including NLRP7, GP6, TNNT1, TNNI3 and DNAAF3. The parents did not have such a deletion and decided to continue the pregnancy. At 37 weeks of gestation, a 2560-g female baby was delivered by cesarean section because of oligohydramnios and decreased fetal movements. The baby manifested cleft palate, micrognathia and retrognathia at birth. She was doing well at age three months. Her body weight was 5.3 Kg (15th-25th centile), and body length was 59.2 cm (25th-50th centile). Renal sonogram showed bilateral mild pelvic dilation. She manifested no psychomotor retardation and no other internal organ abnormalities during pediatric follow-ups.
CONCLUSIONS: A 19q13.42-q13.43 microdeletion can be associated with micrognathia, retrognathia, cleft palate and bilateral pyelectasis at birth.

Temporomandibular joint (TMJ) ankylosis in pediatric patients is rare and may cause severe micrognathia and obstructive sleep apnea syndrome. The present study reports on the treatment and 4-year follow-up of a pediatric patient with early-onset bilateral TMJ ankylosis and severe secondary micrognathia, as well as obstructive sleep apnea syndrome. A typical \'bird face\' appearance was noted with severe mandible retrognathism and a significant convex facial profile. The treatment of this patient involved TMJ ankylosis release with condylectomy and simultaneous bilateral mandibular distraction osteogenesis, which enabled the surgeons to simultaneously reconstruct the neocondyle and correct facial malformations. Following treatment, the micrognathia was corrected and the oropharyngeal airway was significantly expanded. However, the maximal incisal opening was limited. During the 4-year follow-up, no signs of mandible retraction were noted and mouth opening increased to 17 mm (passive) compared with the inability to open that was noted immediately following surgery. A certain degree of MIO shrinkage was identified in the patient. In such cases of TMJ ankylosis, early post-operative exercise, active post-operative physiotherapy and stringent follow-up are essential to prevent post-operative shrinkage and adhesions.