Faculty Bibliography

Lambdoid craniosynostosis (CS) is a congenital anomaly resulting from premature fusion of the cranial suture between the parietal and occipital bones. Predominantly sporadic, it is the rarest form of CS and its genetic etiology is largely unexplored. Exome sequencing of 25 kindreds, including 18 parent-offspring trios with sporadic lambdoid CS, revealed a marked excess of damaging (predominantly missense) de novo mutations that account for ~ 40% of sporadic cases. These mutations clustered in the BMP signaling cascade (P = 1.6 × 10^-7), including mutations in genes encoding BMP receptors (ACVRL1 and ACVR2A), transcription factors (SOX11, FOXO1) and a transcriptional co-repressor (IFRD1), none of which have been implicated in other forms of CS. These missense mutations are at residues critical for substrate or target sequence recognition and many are inferred to cause genetic gain-of-function. Additionally, mutations in transcription factor NFIX were implicated in syndromic craniosynostosis affecting diverse sutures. Single cell RNA sequencing analysis of the mouse lambdoid suture identified enrichment of mutations in osteoblast precursors (P = 1.6 × 10^-6), implicating perturbations in the balance between proliferation and differentiation of osteoprogenitor cells in lambdoid CS. The results contribute to the growing knowledge of the genetics of CS, have implications for genetic counseling, and further elucidate the molecular etiology of premature suture fusion.

BACKGROUND:Many cleft centers incorporate NasoAlveolar Molding (NAM) into their presurgical treatment protocols. However, there are limited data on eligible patients who do not receive or complete NAM. This study characterizes the demographics associated with non-utilization or completion of NAM. METHODS:A single-institution retrospective review was performed of all patients with cleft lip and alveolus undergoing primary unilateral and bilateral cleft lip repair from 2012-2020. Patients were grouped based on utilization or non-utilization of NAM. Demographic and treatment data were collected, including documented reasons for not pursuing or completing NAM. RESULTS: < .001). CONCLUSIONS:Common reasons for non-utilization of NAM include well-aligned cleft alveolus, medical complexity, and late presentation. Early presentation is an important modifiable factor affecting rates of NAM utilization.

OBJECTIVE:The aim of this study was to evaluate the outcomes of orthognathic surgery (OGS) in patients with craniofacial microsomia (CFM) who had previously undergone mandibular distraction osteogenesis (MDO). DESIGN/METHODS:A retrospective cohort study was performed including all patients with CFM who were treated with OGS at a single institution between 1996 and 2019. The clinical records, operative reports, and cone beam computed tomography (CBCT) scans were reviewed. CBCT data before OGS (T1), immediately after OGS (T2), and at long-term follow-up (T3) were analyzed using Dolphin three-dimensional software to measure the occlusal cant and chin point deviation. RESULTS:  =  .808). CONCLUSIONS:Within the limitations of this study, these findings suggest that OGS after MDO in patients with CFM can produce stable results.

Objective: Compare short term surgical outcomes and trends in cleft lip repair with or without gingivoperiosteoplasty (GPP). Design: Retrospective review of the ACS NSQIP-Pediatric database from 2014 to 2019. Patients: Patients between 2 and 18 months of age undergoing any initial cleft lip repair, with or without GPP, were selected via relevant CPT^® codes. Main Outcome Measures: Patient demographics, comorbidities, 30-day readmissions and post-operative complications are assessed. Results: From 2014 to 2019, a total of 6269 patients were identified, of which 6.67% underwent GPP (n = 418). Patients undergoing GPP were significantly older with an average age of 9 months compared to 5 months in the non-GPP group (P <.001). Co-morbidities were similar amongst both cohorts, although patients undergoing GPP were more likely to have a higher ASA class (P =.006), cardiac risk factors (P =.012) and syndromic diagnosis (P <.001). There were no differences in 30-day short term surgical outcomes. GPP was associated with increased operative time by ~25 minutes when compared to cleft lip repair alone (P <.001). Conclusion: GPP was not associated with increased 30-day postoperative complications, readmission, reoperation, or total length of hospital stay, and was associated with an increased operative time of 25 minutes. Children undergoing GPP were significantly older in age and were more likely to have a higher ASA class/cardiac risk factors.

BACKGROUND:Vascularized composite allotransplantation (VCA) has redefined the frontiers of plastic and reconstructive surgery. At the cutting edge of this evolving paradigm, we present the first successful combined full face and bilateral hand transplant (FT-BHT). METHODS:A 21-year-old man with sequelae of an 80% total body surface area burn injury sustained following a motor vehicle accident presented for evaluation. The injury included full face and bilateral upper extremity composite tissue defects, resulting in reduced quality of life and loss of independence. Multidisciplinary evaluation confirmed eligibility for combined FT-BHT. The operative approach was validated through 11 cadaveric rehearsals utilizing computerized surgical planning. Institutional review board and organ procurement organization approvals were obtained. The recipient, his caregiver, and the donor family consented to the procedure. RESULTS:Combined full face (eyelids, ears, nose, lips, and skeletal subunits) and bilateral hand transplantation (forearm level) was performed over 23 hours on August 12-13th, 2020. Triple induction and maintenance immunosuppressive therapy and infection prophylaxis were administered. Plasmapheresis was necessary postoperatively. Minor revisions were performed over seven subsequent operations, including five left upper extremity, seven right upper extremity, and seven facial secondary procedures. At eight months, the patient is approaching functional independence and remains free of acute rejection. He has significantly improved range of motion, motor power, and sensation of the face and hand allografts. CONCLUSION/CONCLUSIONS:Combined FT-BHT is feasible. This is the most comprehensive VCA procedure successfully performed to date, marking a new milestone in plastic and reconstructive surgery for patients with otherwise irremediable injuries.

OBJECTIVE:Primary cleft nasal repair can include septal reconstruction. We hypothesize that primary cleft septoplasty and adult septoplasty have fundamental differences that render these procedures as distinct surgical entities. DESIGN/METHODS:Systematic review of the PubMed, Cochrane, and Embase databases performed on pediatric cleft and general adult septoplasty techniques through December 2021. (PROSPERO ID CRD42022295763). MAIN OUTCOME MEASURES/METHODS:Collected data included information on septal dissection, septal detachment, and management of the bony and cartilaginous septum. RESULTS:Twenty-eight pediatric cleft septoplasty and 229 adult septoplasty studies were included. Dissection in primary cleft septoplasty was limited to the anterocaudal septum, while secondary cleft septoplasty and adult septoplasty techniques entailed wide exposures of the cartilaginous septum with or without exposure of the perpendicular plate of the ethmoid. In primary cleft septoplasty, detachment of the septum was mostly limited to the nasal spine and anterior base of the cartilaginous septum, while secondary cleft septoplasty and adult septoplasty included detachment from the vomer, and ethmoid. In the few reports of cartilage excision during primary cleft septoplasty, removal was limited to the anterior inferior border of the septum, while secondary cleft septoplasty and adult septoplasty included excision of the cartilaginous and bony septum. CONCLUSION/CONCLUSIONS:Primary cleft septoplasty is distinct from septoplasty performed on facially mature patients. More specifically, septal dissection and detachment are limited to the anterior caudal area during primary lip repair, with rare removal of cartilage or bone. Given these differences, the authors suggest the term "septal reset" to describe septoplasty performed during primary cleft nasal repair.

BACKGROUND:Nonsyndromic craniosynostosis is one of the most common anomalies treated by craniofacial surgeons. Despite optimal surgical management, nearly half of affected children have subtle neurocognitive deficits. Whereas timing and type of surgical intervention have been studied, the possibility of genetic influence on neurodevelopment in nonsyndromic craniosynostosis patients remains unexplored. METHODS:The authors performed whole-exome sequencing for 404 case-parent trios with sporadic nonsyndromic craniosynostosis. Statistical analyses were performed to assess the burden of de novo mutations in cases compared to both expectation and 1789 healthy control trios. Individuals with and without each mutation class were analyzed, and the presence or absence of various types of neurodevelopmental delay were recorded alongside demographic information. RESULTS:The authors identified a highly significant burden of damaging de novo mutations in mutation-intolerant [probability of loss of function intolerance (pLI) >0.9] genes in nonsyndromic craniosynostosis probands (p = 5.9 × 10-6). Children with these mutations had a two-fold higher incidence of neurodevelopmental delay (p = 0.001) and a more than 20-fold greater incidence of intellectual disability (p = 7.2 × 10-7), and were 3.6-fold more likely to have delays that persisted past 5 years of age (p = 4.4 × 10-4) in comparison with children with nonsyndromic craniosynostosis without these mutations. Transmitted loss of function mutations in high-pLI genes also conferred a 1.9-fold greater risk of neurodevelopmental delay (p = 4.5 ×10-4). CONCLUSIONS:These findings implicate genetic lesions concurrently impacting neurodevelopment and cranial morphogenesis in the pathoetiology of nonsyndromic craniosynostosis and identify a strong genetic influence on neurodevelopmental outcomes in affected children. These findings may eventually prove useful in determining which children with nonsyndromic craniosynostosis are most likely to benefit from surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, III.

OBJECTIVES/OBJECTIVE:Cleft lip repair has traditionally been performed as an inpatient procedure. There has been an interest toward outpatient cleft lip repair to reduce healthcare costs and avoid unnecessary hospital stay. We report surgical outcomes following implementation of an ambulatory cleft lip repair protocol and hypothesize that an ambulatory repair results in comparable safety outcomes to inpatient repair. DESIGN/SETTING/METHODS:This is a single-institution, retrospective study. PATIENTS/PARTICIPANTS/METHODS:Patients undergoing primary unilateral (UCL) and bilateral (BCL) cleft lip repair from 2012 to 2021 with a minimum 30-day follow-up. A total of 226 patients with UCL and 58 patients with BCL were included. INTERVENTION/METHODS:Ambulatory surgery protocol in 2016. OUTCOME MEASURES/METHODS:Variables include demographics and surgical data including 30-day readmission, 30-day reoperation, and postoperative complications. RESULTS:There were no differences in rates of 30-day readmission, reoperation, wound complications, or postoperative complications between the pre- and post-protocol groups. Following ambulatory protocol implementation, 80% of the UCL group and 56% of the BCL group received ambulatory surgery. Average length of stay dropped from 24 h pre-protocol to 8 h post-protocol. The 20% of the UCL group and 44% of the BCL group chosen for overnight stay had a significantly higher proportion of congenital abnormalities and higher American Society of Anesthesiology (ASA) class. Reasons for overnight stay included cardiac/airway monitoring, prematurity, and monitoring of comorbidities. There were no differences in surgical outcomes between the ambulatory and overnight stay groups. CONCLUSIONS:An ambulatory cleft lip repair protocol can significantly reduce average length of stay without adversely affecting surgical outcomes.

Background/Purpose: After LeFort I advancement surgery, soft tissue changes are unpredictable, especially in patients with orofacial clefts, as scar tissue from primary repair can alter soft tissue responses. Therefore, this study aimed to measure and evaluate soft tissue response following LeFort I advancement in skeletally matured patients with complete cleft lip and palate (CLP). Methods/Description: The cohort of 26 patients with non-syndromic CLP who underwent Le Fort I osteotomy between 2013 and 2019 and met the inclusion criteria. Patients were included if they had lateral cephalograms or CBCT at pre-operative (T1), immediately post-operative (T2), and one-year follow-up (T3). Patients who underwent nose/lip revision surgery before T3 were excluded. Four skeletal and dental hard-tissue (ANS, point A; A-point, upper incisor most labial; U1-most, upper incisor edge; U1-tip) and 5 softtissue (tip of nose or pronasale; Prn, subnasale; Sn, superior labial sulcus; SLS, upper lip anterior or labrale superius; LS, and stomion superius; SIMS) landmarks were digitized and measured. For the outcome analyses, 5 ratios of soft- to hard-tissue changes (Prn/ANS, Sn/A-point, SLS/A-point, LS/U1-most, and SIMS/ U1-tip) were calculated for each group, and associations between hard-and-soft tissue counterparts were assessed using Pearson correlation coefficient (r).
Result(s): Sixteen patients had UCLP, and 10 patients had BCLP. At one-year follow-up (T1-T3), the mean advancement in UCLP and BCLP groups at ANS were 4.4+/-3 and 4.7+/-3.9 mm, from point A were 6.6+/-2.5, 8.8+/- 2.6 mm, respectively. The mean horizontal changes of the corresponding soft tissue anatomy, Prn, were 2.7 +/-1.7, 4.6+/-3.5 mm, from Sn, were 3.9+/-1.9, 6.2+/-2.4. mm, and from SLS were 5.2+/-2.5, 7.4+/-2.8 mm. The mean advancement in at upper incisor most labial were 7.2+/-2.7 and 8.4+/-2.4 mm, and from the upper incisal edge were 7.5+/-2.9 and 8.4+/-2.7. mm. The mean horizontal changes of the soft tissue counterpart, LS, were 5.6+/-2.9, 7.9+/- 3.7 mm, and SIMS were 6.0+/-3.2, 7.3+/- 2.7 mm. All skeletal, dental, and soft tissue advancements from T1-T3 were significant (P< 0.01) except for Sn and LS in both groups and SIMS in UCLP group. For ratio and correlation analyses in UCLP and BCLP groups, Prn/AND were 0.48 (r=0.40) and (r=0.00), Sn/A-point were 0.58 (r=0.79) and 0.70 (r=0.77), SLS/A-point were 0.79 (r=0.82) and 0.85 (r=0.80), LS/U1-most were 0.74 (r=0.92) and 0.96 (r=0.74), and SIMS/U1-tip were 0.78 (r=0.75) and 0.82(r=0.67), respectively. All associations except for Prn/ANS were statistically significant (P< 0.01).
Conclusion(s): This study demonstrated a linear relationship between soft- and hard-tissue changes in the maxillary landmarks following LeFort I advancement in patients with complete cleft lip and palate (UCLP and BCLP)