Roberts syndrome (RBS) is an autosomal recessive disorder with profound growth deficiency and limb reduction caused by ESCO2 loss-of-function variants. Here, we elucidate the pathogenesis of limb reduction in an Esco2fl/fl;Prrx1-CreTg/0 mouse model using bulk- and single-cell-RNA-seq and gene co-expression network analyses during embryogenesis. Our results reveal morphological and vascular defects culminating in hemorrhage of mutant limbs at E12.5. Underlying this abnormal developmental progression is a pre-apoptotic, mesenchymal cell population specific to mutant limb buds enriched for p53-related signaling beginning at E9.5. We then characterize these p53-related processes of cell cycle arrest, DNA damage, cell death, and the inflammatory leukotriene signaling pathway in vivo. In utero treatment with pifithrin-α, a p53 inhibitor, rescued the hemorrhage in mutant limbs. Lastly, significant enrichments were identified among genes associated with RBS, thalidomide embryopathy, and other genetic limb reduction disorders, suggesting a common vascular etiology among these conditions.

The field of frontofacial surgery has advanced considerably, building on the pioneering techniques of Paul Tessier, with computerized surgical planning (CSP) emerging as a critical component. CSP has enhanced the precision and efficiency of surgeries for craniofacial dysostoses and hypertelorism, resulting in improved outcomes. This review delves into the importance of understanding orbital anatomy and the crucial bony and soft tissue landmarks essential to the application of CSP in frontofacial procedures, encompassing Le Fort III and monobloc advancements, as well as the correction of hypertelorism.

UNASSIGNED: Orbital hypertelorism is a rare congenital condition caused by craniofacial malformations. It consists of complete orbital lateralization, characterized by an increase in distance (above the 95th percentile) of the inner canthal (ICD), outer canthal, and interpupillary distances. It can be approached surgically, and the main techniques are box osteotomy and facial bipartition. The surgical procedure is usually performed before the age of 8. We describe here two patients who underwent late surgical correction using the box osteotomy technique.
UNASSIGNED: Patient 1: A 13-year-old female presenting isolated hypertelorism with 5 cm ICD and left eye amblyopia. Patient 2: A 15-year-old female with orbital hypertelorism, 4.6 cm ICD, and nasal deformity. Both patients underwent orbital translocation surgery and had no neurological disorders.
UNASSIGNED: The article reports two cases of isolated hypertelorism treated late with the box osteotomy technique. Both surgeries were successful, with no postoperative complications. It appears that it is possible to obtain good surgical results even in patients who have not been able to undergo surgery previously.

To determine the effect of midface surgery on soft tissue changes and their relationship to hard tissue changes in patients with syndromic craniosynostosis. A retrospective analysis of patients who had undergone Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB) was conducted. A 3D soft tissue mesh was generated from the preoperative scan and registered to the postoperative scan, after which the advancement was visualised. A total of 68 patients were included: 28 had undergone LFIII, 27 MB, and 13 FB. The included diagnoses were Apert (n = 23), Crouzon (n = 34), and craniofrontonasal syndrome (n = 11). After LFIII, most soft tissue advancement was seen around subnasale and pronasale (mean 15.1 ± 5.9 mm and 14.7 ± 5.7 mm, at age 7-12 years). After MB, a greater hard tissue than soft tissue advancement was seen for most landmarks, showing a high positive correlation. In patients undergoing FB without distraction (n = 10), mean preoperative inter-canthal distance was 48.9 mm, this reduced by 6.9 mm postoperatively. This study provides a comprehensive overview of the outcomes after midface surgery using 3D quantification for a better understanding of the soft tissue changes and their relationship to hard tissue changes.

暂无摘要。

To determine the skeletal changes after midface surgery in patients with syndromic craniosynostosis who underwent Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB). This was a retrospective study including 75 patients: 33 treated by LFIII, 29 by MB, and 13 by FB. Twenty-five had a diagnosis of Apert, 39 Crouzon, and 11 craniofrontonasal syndrome. A three-dimensional mesh was created from the preoperative scan and registered to the postoperative scan to visualise the advancement. LFIII at age 7-12 years effectuated a higher mean advancement in the maxillary (15.5 mm) and zygomatic (7.6 mm) regions when compared to ≥13 years (10.2 mm and 5.5 mm). After MB, mean advancement of the fronto-orbital region was higher at <7 years (16.4 mm), and similarly lower at ages 7-12 (13.8 mm) and ≥13 (12.5 mm). The mean preoperative inter-dacryon distance (34.4 ± 4.4 mm) was reduced by 8.7 ± 4.2 mm after FB without distraction (n = 10). More advancement was seen when midface surgery was performed at a younger age, due to more severe cases and a desire for overcorrection. The highest mean advancement was observed in the fronto-orbital region. Antero-inferior rotational movement was seen after all three techniques.

Sonic hedgehog signaling molecule (SHH) is a key molecule in the cilia-mediated signaling pathway and a critical morphogen in embryogenesis. The association between loss-of-function variants of SHH and holoprosencephaly is well established. In mice experiments, reduced or increased signaling of SHH have been shown to be associated with narrowing or excessive expansion of the facial midline, respectively. Herein, we report two unrelated patients with de novo truncating variants of SHH presenting with hypertelorism rather than hypotelorism. The first patient was a 13-year-old girl. Her facial features included hypertelorism, strabismus, telecanthus, malocclusion, frontal bossing, and wide widow\'s peak. She had borderline developmental delay and agenesis of the corpus callosum. She had a nonsense variant of SHH: Chr7(GRCh38):g.155802987C > T, NM_000193.4:c.1302G > A, p.(Trp434*). The second patient was a 25-year-old girl. Her facial features included hypertelorism and wide widow\'s peak. She had developmental delay and agenesis of the corpus callosum. She had a frameshift variant of SHH: Chr7(GRCh38):g.155803072_155803074delCGGinsT, NM_000193.4:c.1215_1217delCCGinsA, p.(Asp405Glufs*92). The hypertelorism phenotype contrasts sharply with the prototypical hypotelorism-holoprosencephaly phenotype associated with loss-of-function of SHH. We concluded that a subset of truncating variants of SHH could be associated with hypertelorism rather than hypotelorism.

暂无摘要。

OBJECTIVE: To explore the genetic basis for a patient with unexplained developmental delay and special facial features.
METHODS: A male patient admitted to the Maternal and Child Health Care Hospital of Gansu Province on May 27, 2021 due to infertility was selected as the study subject. Clinical data of the patient was collected, and genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing.
RESULTS: The patient was found to harbor a 2.54 Mb deletion in 1p36.33p36.32 and a heterozygous c.1123G>C (p.E375Q) variant of the CHD3 gene, neither of which was detected in his parents.
CONCLUSIONS: The patient was diagnosed with Snijders Blok-Campeau syndrome in conjunct with 1p36 deletion syndrome, which has enabled genetic counseling for his family.

Diprosopus is a congenital anomaly in which partial or complete duplication of craniofacial structures occurs. Because it is rare, the mortality rate is high, and information concerning this anomaly is scarce. This study describes a case of human diprosopus in a 9-year-old male individual, who has severe complications associated with the central nervous, cardiovascular, respiratory, and digestive systems. Since birth, he has been monitored in a specialized hospital environment, where he has undergone several surgeries and multidisciplinary treatments. Regarding the craniofacial aspects, he had agenesis of the corpus callosum, floor of the nasal cavity, and floor of the anterior cranial fossa, in addition to the presence of bone dysplasia, ocular hypertelorism and cleft palate with nasal and oral teratoma. Regarding dental characteristics, the patient has duplication of the maxilla, mandible, tongue, and some teeth. After complementary imaging exams, several supernumerary teeth were found, with some being impacted and in complex regions, with an indication for extraction due to the risks of impaction, irruptive deviation, root resorption, and associated cystic or tumoral lesions. Because of the numerous complications, knowledge, and preparation of the entire team is necessary for the correct management of the case.