Cleft lip and cleft palate are among the most common congenital anomalies and are the result of incomplete fusion of embryonic craniofacial processes or palatal shelves, respectively. We know that genetics play a large role in these anomalies but the list of known causal genes is far from complete. As part of a larger sequencing effort of patients with micrognathia and cleft palate we identified a candidate variant in transforming growth factor beta receptor 2 (TGFBR2) which is rare, changing a highly conserved amino acid, and predicted to be pathogenic by a number of metrics. The family history and population genetics would suggest this specific variant would be incompletely penetrant, but this gene has been convincingly implicated in craniofacial development. In order to test the hypothesis this might be a causal variant, we used genome editing to create the orthologous variant in a new mouse model. Surprisingly, Tgfbr2V387M mice did not exhibit craniofacial anomalies or have reduced survival suggesting this is, in fact, not a causal variant for cleft palate/ micrognathia. The discrepancy between in silico predictions and mouse phenotypes highlights the complexity of translating human genetic findings to mouse models. We expect these findings will aid in interpretation of future variants seen in TGFBR2 from ongoing sequencing of patients with congenital craniofacial anomalies.

Pierre Robin Sequence (PRS), a rare congenital disorder, is a triad of micrognathia, glossoptosis, and tongue based airway obstruction (TBSO). It may occur as isolated anomaly (iPRS) or as a part of a syndrome (sPRS), like that seen in association with Stickler Syndrome. Approximately 20% of children with PRS have congenital heart diseases. To the best of our knowledge this case of a one-day old infant is the first one to be reported as having two heart defects; patent ductus arteriosus and patent foramen ovale in Pierre Robbin Sequence child.

Edwards syndrome, also known as trisomy 18, is a rare chromosomal disorder associated with multiple congenital anomalies and high morbidity. This report presents the case of a three-month-old female infant diagnosed with Edwards syndrome, presenting classic phenotypic features, including low-set ears, micrognathia, and a rocker bottom foot. The infant\'s condition was further complicated by cardiac abnormalities and respiratory distress, necessitating a comprehensive, multidisciplinary approach involving pediatricians, cardiologists, and orthopedic specialists. The diagnostic journey involved addressing challenges related to respiratory distress syndrome, bronchiolitis, and cardiac complications. The management approach underscored the significance of individualized care tailored to the patient\'s unique needs. Genetic counseling played a pivotal role in providing essential support to the family facing the complexities associated with Edwards syndrome. This case report highlights the intricacies of Edwards syndrome and contributes to the ongoing discourse on refining clinical strategies for enhanced care and compassionate support. Additionally, it emphasizes the need for further research to advance our understanding of this condition and guide future interventions.

The Robin sequence is a congenital anomaly characterized by a triad of features: micrognathia, glossoptosis, and airway obstruction. This comprehensive historical review maps the evolution of approaches and appliances for its treatment from the past to the current modern possibilities of an interdisciplinary combination of modern engineering, medicine, materials, and computer science combined approach with emphasis on designing appliances inspired by nature and individual human anatomy. Current biomimetic designs are clinically applied, resulting in appliances that are more efficient, comfortable, sustainable, and safer than legacy traditional designs. This review maps the treatment modalities that have been used for patients with a Robin sequence over the years. Early management of the Robin sequence focused primarily on airway maintenance and feeding support, while current management strategies involve both nonsurgical and surgical interventions and biomimetic biocompatible personalized appliances. The goal of this paper was to provide a review of the evolution of management strategies for patients with the Robin sequence that led to the current interdisciplinary biomimetic approaches impacting the future of Robin Sequence treatment with biomimetics at the forefront.

OBJECTIVE: To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers.
METHODS: The Children\'s Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge.
RESULTS: Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both).
CONCLUSIONS: Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.

In growing children, temporomandibular joint (TMJ) ankylosis and septic arthritis are uncommon. Retrognathia and micrognathia affect airway patency and can cause obstructive sleep apnea (OSA). No unified diagnostic criteria have been established for the management of this pathology. We describe the first case of treatment for pediatric TMJ ankylosis and severe OSA due to neonatal group B streptococcal septic TMJ arthritis. Untreated pathological changes in the TMJ will eventually lead to ankylosis. Among children, this will include facial growth disturbances leading to mandibular retrognathia, reduction in the oropharyngeal spaces, and OSA. Our patient had severe OSA with an apnea-hypopnea index of 24.9 events/h and oxygen saturation nadir of 73% as measured by polysomnography. She was treated successfully according to Andrade protocol. This is the first report of pediatric OSA due to TMJ ankylosis following neonatal group B streptococcal septic arthritis.
BACKGROUND: Pesis M, Goldbart A, Givol N. Surgical correction of neonatal obstructive sleep apnea due to a temporomandibular joint ankylosis. J Clin Sleep Med. 2024;20(1):173-179.

Obstructive sleep apnoea (OSA) is identified as repetitive and intermittent upper airway collapse or narrowing during sleep. Skeletal advancement through maxillomandibular surgery remains the most effective surgical treatment for OSA but is radical with certain relapse rate. Distraction Osteogenesis of mandible is a single-jaw surgical treatment alternative to bi-jaw surgeries having lesser complications. This case report describes successful management of a 46-year-old patient who reported with a chief complain of obstruction in breathing while sleeping since one year. Obstructive Sleep Apnoea (OSA) secondary to a retrognathic mandible was the final diagnosis, which was successfully treated by Distraction Osteogenesis (DO) of the mandible. The case showed enhancement in airway by 13mm and marked forward movement of Point-B (SNB increased by 6 degrees). The Epworth Sleepiness Scale value decreased from 19mm to 8 mm indicating substantial increase in the airway with stable results after 18 months of follow-up (elimination of symptoms and subsequent sound sleep). Distraction osteogenesis is an effective and reliable method to treat obstructive sleep apnoea secondary to retrognathic mandible.

Second-trimester 2D ultrasound (US) assessment of the fetal anatomy, as proposed by worldwide guidelines, allows detecting the majority of fetal malformation. However, the detection rates of fetal facial anomalies seem to still be low, mostly in cases of isolated facial malformation. The purpose of this research was to assess and analyze the concordance between the antenatal imaging findings from second-trimester US screening and the results of fetal postmortem autopsy. Between January 2010 and January 2020, there were 43 cases where fetuses with prenatal ultrasound diagnosis of a face abnormality, associated or not with a genetic syndrome or chromosomal disorder, following intrauterine death (IUD) or termination of pregnancy (TOP) after the 13 weeks of pregnancy, underwent autopsy in the Pathological Anatomy section of Bari Polyclinic specializing in feto-placental autopsies. The diagnosis of the fetal facial defects at ultrasound was compared with the findings at autopsy in all cases. A very high level of agreement between prenatal ultrasound and autopsy findings was found for facial abnormalities associated with genetic syndromes or numerical abnormality of chromosomes. A lower level of concordance was instead found in isolated facial defects or those associated with other organ anomalies, but not associated with genetic syndrome or numerical chromosome anomaly. A detailed examination of aborted fetuses led to successful quality control of early-second-trimester ultrasound detection of facial anomalies; however, it was less accurate for the isolated ones. It is, thus, reasonable to propose a systematic early-second-trimester prenatal ultrasound screening for facial anatomy by operators specialized in fetal medicine field, using 2D, 3D, and 4D techniques (two-, three-, and four-dimensional ultrasound).

Introduction: Considering the positive effects of a low-level laser on new bone formation, we aimed to investigate the effects of a low-level laser in the treatment of patients with class II mandibular deficiency treated with Farmand functional appliance. Methods: Twenty-two growing patients aged 10-14 years were randomly divided into \"Farmand\" and \"Farmand+Laser\" groups. All patients were treated with Farmand functional appliance. Patients in the \"Farmand+laser\" group were exposed to laser irradiation (980 nm, 100 mw, 4 points around temporomandibular joints, 100 seconds each point) weekly for three months after 3-4 weeks of using the appliance. Lateral cephalometry radiographs were taken from all patients before and after the treatment period, and changes in skeletal and dental parameters were measured. Results: The association of the particular laser irradiation with the functional appliance led to a greater increase in the effective length of the mandible (Co-Gn, P=0.048), the anterior sagittal position of the mandible (SNB, P=0.029), and the length of the ramus (Co-Go, P=0.028), and it showed a further decrease in the discrepancy between the jaws (ANB, P=0.000) compared with the functional appliance alone. Conclusion: The application of the laser with the chosen parameters and protocol in conjunction with the functional appliance improved the effects of the functional appliance and reduced the discrepancy between the two jaws.

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。.