Bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap technique for nonsyndromic unilateral coronal synostosis.

Background: The goals of operative treatment for unilateral coronal synostosis (UCS) are to improve appearance and allow unrestricted brain growth. However, for severe unilateral premature closure of the coronal suture, existing methods do not address the compression of the brain or expand the volume of the skull cavity. We report our retrospective experience with bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap (CVR + FFBF) technique and the resulting changes in the anterior cranial vault asymmetry index (ACVAI) and intracranial volume. Methods: Twenty patients with UCS who underwent bilateral fronto-orbital advancement combined with CVR + FFBF technique from April 2014 to May 2019 were included. Surgical efficacy was evaluated by the ACVAI and intracranial volume before the operation, 1 week after the operation, and at the last follow-up (average 19.8 months; range, 12 to 40 months). The measurement data are presented as the mean ± standard deviation and were statistically analyzed by t-test. Results: The ACVAI was 9.07%±3.55% before the operation, 3.56%±3.42% 1 week after the operation, and 3.13%±2.41% at the last follow-up. The ACVAI 1 week after the operation was significantly lower than that before the operation (t=4.827, P<0.001). There was no significant difference between the ACVAI 1 week after the operation and at the last follow-up (t=0.660, P=0.517). The intracranial volume was 1,027.85±112.25 mL in patients before the operation and 1,131.92±161.71 mL in the normal control group, which was a statistically significant difference (t=2.364, P=0.023). The intracranial volume significantly increased 1 week after surgery: 1,081.62±111.10 mL (t=8.703, P<0.001), and this trend continued at the last follow-up (1,386.90±119.30 mL) similarly to the normal control group (1,438.22±89.28 mL). At the last follow-up, there was no significant difference between the two groups (t=1.540, P=0.132). Conclusions: For the treatment of UCS, bilateral fronto-orbital advancement combined with CVR + FFBF technique offers functional and cosmetic outcomes in terms of intracranial volume expansion and fronto-orbital symmetry.

Preventive surgery for asymptomatic spinal lipomas in children.

AIM: To explore the clinical effect and significance of preventive surgery of asymptomatic spinal lipo-mas in children. MATERIAL AND METHODS: We retrospective analysis of clinical data of 168 cases with asymptomatic spinal lipoma from April 2001 to June 2019 in our hospital. The patients were aged from 1.5 months to 15 years (the average age was 7 months), and there were no neurological symptoms such as pain, incontinence, and / or bilateral lower limb dysfunction before surgery. The surgical proce-dure included: completely removed the lipomas in subcutaneous and extramedullary tissues of the spinal cord, subtotal resection of intraspinal fat, cutting and separating the spinal cord including the medullary cones from the dura sac to release the tethered cord. RESULTS: For the 168 children with spinal lipomas included in the study, complete resection was undertaken for the dorsal spinal lipomas , subtotal resection was taken for the transitional and chaotic spinal lipomas .Subcutaneous effusion caused by cerebrospinal fluid leakage occurred in 5 cases after surgery, which was cured after multiple puncture and aspiration. Six patients developed mild in-continence immediately after the operation, 5 of whom completely returned to normal within 1 month, and 1 had no relief of symptoms.159 of the 168 patients were followed up for 3 to 19 years (the median follow-up time was 76 months). Long-term postoperative symptoms occurred in 13 patients (7.7%), including 12 cases of spinal cord retethering and 1 case of lipoma enlargement. CONCLUSION: Preventive surgery can reduce the incidence of neurological dysfunction in children with asymp-tomatic spinal lipomas in the future.

Overactive autophagy is a pathological mechanism underlying premature suture ossification in nonsyndromic craniosynostosis.

Nonsyndromic craniosynostosis (NSC) is the most common craniosynostosis with the primary defect being one or more fused sutures. In contrast to syndromic craniosynostosis, the etiopathogenesis of NSC is largely unknown. Here we show that autophagy, a major catabolic process required for the maintenance of bone homeostasis and bone growth, is a pathological change associated with NSC. Using calvarial suture mesenchymal cells (SMCs) isolated from the fused and unfused sutures of NSC patients, we demonstrate that during SMC differentiation, the level of the autophagosomal marker LC3-II increases as osteogenic differentiation progresses, particularly at differentiation day 7, a stage concurrent with mineralization. In fused SMCs, autophagic induction was more robust than that in unfused SMCs, which consequently led to enhanced mineralized nodule formation. Perturbation of autophagy with rapamycin or wortmannin promoted or inhibited the ossification of SMCs, respectively. Our findings suggest that autophagy is essential for the osteogenic differentiation of SMCs and that overactive autophagy is a molecular abnormality underlying premature calvarial ossification in NSC.

Identification and analysis of the genetic causes in nine unrelated probands with syndromic craniosynostosis.

Syndromic craniosynostosis is a group of multiple conditions with high heterogeneity, and many rare syndromes still remain to be characterized. To identify and analyze causative genetic variants in nine unrelated probands mainly manifested as syndromic craniosynostosis, we reviewed the relevant medical information of the patients and performed the whole exome sequencing, further verified with Sanger sequencing and parental background. Bioinformatics analysis was used to evaluate the potential deleterious or benign effect of each genetic variant through evolutionary conservation alignment, multi-lines of computer predication and the allele frequency in population dataset (control and patient). The Standards and guidelines from American College of Medical Genetics and Genomics was used to classify and interpret the pathogenicity for each genetic variant. All the nine probands were found to carry the possibly causative variants, among which three variants including two missense mutations (c.3385C>T in IFT122 gene, c.3581A>G in SMC1A gene) and a frameshift mutation (c.434dupA in TWIST1 gene) have never been reported in patients before. We suggested Cornelia de Lange syndrome caused by SMC1A variant is a neglected syndromic craniosynostosis. Our study not only expanded genotypic and phenotypic spectrum of the rare syndromes, but also confirmed that there existed an underlying genetic mechanism. We emphasized that deliberate selection of both the potential candidates and comprehensive detection methods for genetic analysis is important to increase the genetic diagnosis yield of syndromic craninosynostosis.