Integrated propranolol, methylprednisolone, and surgery in managing a rare case of infantile hemangioma with concurrent cleft lip and palate.
ABSTRACT: Infantile hemangioma (IH) with concurrent cleft lip and palate is a rare case. Surgical management is often considered as the best management for infantile hemangioma with concurrent cleft lip and palate. However, considering the functionality aspect and aesthetic appearance, a plastic surgeon can also consider non-surgical management without interrupting the surgical timeline for the cleft lip and palate. This case report aimed to describe the role of oral propranolol and oral methylprednisolone for infantile hemangioma with concurrent cleft lip and palate alongside the surgical management for cleft lip and palate. A 2-month-old presented with complaints of swelling in her right upper nose and cheek along with cleft lip and palate. She was treated with oral propranolol and oral methylprednisolone. Labioplasty was performed when she was three months old. Palatoplasty and nasorraphy were done when she was one year old. A significant reduction of the hemangioma was seen and the corrective procedures showed a good result. The use of propranolol and methylprednisolone for infantile hemangioma in our patient shows a good result even when combined with labioplasty, palatoplasty, and nasorraphy for cleft lip and palate. The management of infantile hemangioma with concurrent cleft lip and palate using oral propranolol and oral methylprednisolone shows a good result with no side effects and can be elaborated with labioplasty, palatoplasty, and nasorraphy, and will not interrupt the cleft lip and palate surgical timeline.
Project description:Importance:Oral propranolol is widely considered to be first-line therapy for complicated infantile hemangioma, but its use in patients with PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome has been debated owing to concerns that the cardiovascular effects of the drug may increase the risk for arterial ischemic stroke. Objective:To assess the incidence of adverse events among patients with PHACE syndrome receiving oral propranolol for infantile hemangioma. Design, Setting, and Participants:This multicenter retrospective cohort study assessed the incidence of adverse events among 76 patients with PHACE syndrome receiving oral propranolol for infantile hemangioma at 11 tertiary care, academic pediatric dermatology practices. Medical records from January 1, 2010, through April 25, 2017, were reviewed. Exposures:Patients received oral propranolol, 0.3 mg/kg/dose or more. Main Outcomes and Measures:The main outcome was the rate and severity of adverse events occurring throughout the course of treatment with oral propranolol, as documented in the medical records. Adverse events were graded from 1 to 5 using a scale derived from the Common Terminology Criteria for Adverse Events and were considered to be serious if they were grade 3 or higher. Results:A total of 76 patients (59 girls and 17 boys; median age at propranolol initiation, 56 days [range, 0-396 days]) met the inclusion criteria. There were no reports of serious adverse events (ie, stroke, transient ischemic attack, or cardiovascular events) during treatment with oral propranolol. A total of 46 nonserious adverse events were reported among 29 patients (38.2%); the most commonly reported nonserious adverse events were sleep disturbances and minor gastrointestinal tract and respiratory tract symptoms. In a comparison with 726 infants who received oral propranolol for hemangioma but did not meet criteria for PHACE syndrome, there was no significant difference in the rate of serious adverse events experienced during treatment (0 of 76 patients with PHACE syndrome and 3 of 726 patients without PHACE syndrome [0.4%]). Conclusions and Relevance:This study found that oral propranolol was used to treat infantile hemangioma in 76 patients with PHACE syndrome and that no serious adverse events were experienced. These data provide support for the safety of oral propranolol in this patient population.
Project description:Isolated cleft lip with or without cleft palate and cleft palate are among the most common human birth defects. Several candidate gene studies on MSX1 have shown significant association between markers in MSX1 and risk of oral clefts, and re-sequencing studies have identified multiple mutations in MSX1 in a small minority of cases, which may account for 1-2% of all isolated oral clefts cases. We explored the 2-Mb region around MSX1, using a marker map of 393 single nucleotide polymorphisms (SNPs) in 297 cleft lip, with or without cleft palate, case-parent trios and 84 cleft palate trios from Maryland, Taiwan, Singapore, and Korea. Both individual markers and haplotypes of two to five SNPs showed several regions yielding statistical evidence for linkage and disequilibrium. Two genes (STK32B and EVC) yielded consistent evidence from cleft lip, with or without cleft palate, trios in all four populations. These two genes plus EVC2 also yielded suggestive evidence for linkage and disequilibrium among cleft palate trios. This analysis suggests that several genes, not just MSX1, in this region may influence risk of oral clefts.
Project description:<h4>Background</h4>Cleft lip with or without cleft palate is one of the most common birth defects and is certainly the most visible. Fistula rate after primary palatoplasty was ranging between 10 and 23% and could be detected in the first three weeks after surgery. The cleft width is the frequent factor which was assumed to correspond to fistula occurrence. This study aimed to find correlation between fistula occurrence with cleft width and palatum width ratio after primary palate repair.<h4>Methods</h4>A prospective cohort study was conducted on 16 subjects, which consisted of 10 males and 6 females. We measured width of cleft palate, width of rest palate and width of palate arch on three level measurements (posterior, junction and anterior). The surgery was performed using the two-flap and three layers suturing technique.<h4>Results</h4>Sixteen patients were enrolled in this study during January and February 2008 . Ten patients were diagnosed with unilateral cleft palate while six patients had bilateral cleft palate. Mean of age was 22.31 ± 5.86 month. Correlation analysis between fistula occurrence and cleft width, cleft width-remnant palate width ratio and cleft width-palate arch width ratio using logistic regression did not show statistical correlation, and the same result was found between fistula occurrence and hemoglobin level, white blood count, nutritional status, cleft type and caries dentis factors (<i>p</i> > 0.05).<h4>Conclusion</h4>Width of the cleft is not a factor associated with fistula occurrence. Two-flap three layers technique could be considered as a simple technique and gives a low rate of fistula occurrence.
Project description:To evaluate the outcomes of care for children by type of oral cleft.Data were collected through structured telephone interviews during 2003 in Iowa with mothers of 2- to 12-year-old children with oral clefts. Interviews with mothers of children with clubfoot and statewide data on Iowa children were used for comparison.Participants included mothers of children in Iowa born between 1990 and 2000 with nonsyndromic oral clefts. Children were identified by the statewide Iowa Registry for Congenital and Inherited Disorders.Rating of cleft care, severity of condition, health status, esthetic outcome, speech, and school performance were evaluated by type of oral cleft.Children with cleft lip and palate were most likely to have their clefts rated as very severe. Children with palatal involvement were reported to have a lower health status and were almost twice as likely to be identified as having a special health care need compared with either children with cleft lip or children statewide. Children with cleft lip had more esthetic concerns; children with palatal involvement had the most speech concerns.Although mothers generally believed their children had received high-quality care, ratings of the children's current health status and outcomes of care varied significantly by type of cleft (cleft lip, cleft palate, and cleft lip and palate). Differences observed in this population-based study support the proposition that cleft type should be considered when examining outcomes of care for children with oral clefts.
Project description:Oral clefts are composed of cleft of the lip, cleft of the lip and palate, or cleft of the palate, and they are associated with a wide range of expression and severity. When cleft of the palate is associated with cleft of the lip with preservation of the primary palate, it defines an atypical phenotype called discontinuous cleft. Although this phenotype may represent 5% of clefts of the lip and/or palate (CLP), it is rarely specifically referred to and its pathophysiology is unknown. We conducted whole exome sequencing (WES) and apply a candidate gene approach to non-syndromic discontinuous CLP individuals in order to identify genes and deleterious variants that could underlie this phenotype. We discovered loss-of-function variants in two out of the seven individuals, implicating FGFR1 and DLG1 genes, which represents almost one third of this cohort. Whole exome sequencing of clinically well-defined subgroups of CLP, such as discontinuous cleft, is a relevant approach to study CLP etiopathogenesis. It could facilitate more accurate clinical, epidemiological and fundamental research, ultimately resulting in better diagnosis and care of CLP patients. Non-syndromic discontinuous cleft lip and palate seems to have a strong genetic basis.
Project description:Infantile hemangiomas can cause significant morbidity during proliferation, yet there is no U.S. Food and Drug Administration-approved treatment. They are believed to form from hemangioma stem cells, which differentiate toward a hemangioma endothelial cell phenotype. Recently, propranolol has demonstrated effectiveness in treating complicated infantile hemangiomas. The authors hypothesize that propranolol facilitates their involution by altering cellular behavior in both hemangioma endothelial and stem cells.Hemangioma endothelial and stem cells were isolated from resected infantile hemangioma specimens. Cells were treated with 100 ?M propranolol for 48 hours, and apoptosis was determined by the presence of annexin V antibody. Proliferation of stem and endothelial cells was assessed after treatment with 50 or 100 ?M propranolol or vehicle, for 72 and 96 hours, respectively. Adipogenesis was induced in stem cells with and without propranolol. Pro-adipogenic genes PPAR?, PPAR?, C/EBP?, C/EBP?, C/EBP?, RXR?, and RXR? were analyzed by quantitative polymerase chain reaction.Annexin V levels were increased in propranolol-treated endothelial cells but not in stem cells. Proliferation of stem and endothelial cells was inhibited by propranolol in a dose-dependent manner. Propranolol-treated stem cells demonstrated accelerated adipogenesis when compared with untreated controls. Transcript levels of C/EBP? (p < 0.05), RXR? (p < 0.05), and PPAR? (p < 0.02) were significantly increased when treated with 50 or 100 ?M propranolol; and C/EBP? (p < 0.05), RXR? (p < 0.05), and PPAR? (p < 0.01) transcripts were increased when treated with 100 ?M propranolol. C/EBP? transcript levels remained unchanged at either dose.Propranolol increased apoptosis of hemangioma endothelial cells, but not stem cells, and accelerated adipogenesis of hemangioma stem cells. Thus, propranolol likely accelerates involution to fibrofatty residuum.
Project description:Van der Woude syndrome (VWS; OMIM 119300) is an autosomal-dominant condition associated with clefts of the lip and/or palate and lower lip pits and is caused by mutations in interferon regulatory factor 6 (IRF6). The standard of practice for children born with cleft lip/palate is surgical repair, which requires proper wound healing. We tested the hypothesis that children with VWS are more likely to have wound complications after cleft repair than children with nonsyndromic cleft lip/palate (NSCLP). Furthermore, we hypothesized that children with VWS have more surgical procedures. A retrospective, case-controlled study was performed. Seventeen children with VWS and 68 matched controls with NSCLP were scored for the presence of wound complications after cleft repair, for the severity of complications, and for number of surgeries from age 0 to 10. Of the 17 children with VWS, 8 had wound complications. Of 68 controls, 13 had wound complications (P = 0.02). Of 8 wound complications in the VWS group, 6 were major, whereas of 13 complications in the control group, 9 were major (P = 0.04). Most wound complications were fistulae and occurred in isolated cleft palate and bilateral cleft lip. The mean number of surgeries in the VWS group was 3.0 compared with 2.8 in the control group (P = 0.67). Our studies suggest that children with VWS have an increased risk for wound complications after cleft repair compared with children with NSCLP. Furthermore, these data support a role for IRF6 in wound healing.
Project description:The decision for lip revision surgery in patients with repaired cleft lip/palate is based on surgeons' subjective evaluation of lip disability. An objective evaluation would be highly beneficial for the assessment of surgical outcomes. In this study, the effects of lip revision on circumoral movements were objectively quantified. The hypothesis was that lip revision increases scarring and impairment. The study was a non-randomized clinical trial that included patients with cleft lip who had revision, patients with cleft lip who did not, and non-cleft control individuals. Three-dimensional facial movements were measured. Revision patients were measured before and after surgery. Other individuals were measured at similar intervals. Regression models were fit to summary measurements, and changes were modeled. Patients with repaired cleft lip/palate had fewer mean movements than control individuals. Lip revision did not worsen mean movements; however, individual patients' movements varied from 'improvement' to 'no change' to 'worse' relative to those of control individuals.
Project description:Propranolol is an approved non-selective ?-adrenergic blocker that is first line therapy for infantile hemangioma. Despite the clinical benefit of propranolol therapy in hemangioma, the mechanistic understanding of what drives this outcome is limited. Here, we report successful treatment of pericardial edema with propranolol in a patient with Hypotrichosis-Lymphedema-Telangiectasia and Renal (HLTRS) syndrome, caused by a mutation in SOX18. Using a mouse pre-clinical model of HLTRS, we show that propranolol treatment rescues its corneal neo-vascularisation phenotype. Dissection of the molecular mechanism identified the R(+)-propranolol enantiomer as a small molecule inhibitor of the SOX18 transcription factor, independent of any anti-adrenergic effect. Lastly, in a patient-derived in vitro model of infantile hemangioma and pre-clinical model of HLTRS we demonstrate the therapeutic potential of the R(+) enantiomer. Our work emphasizes the importance of SOX18 etiological role in vascular neoplasms, and suggests R(+)-propranolol repurposing to numerous indications ranging from vascular diseases to metastatic cancer.
Project description:No consensus exists on the optimal treatment protocol for orofacial clefts or the optimal timing of cleft palate closure. This study investigated factors influencing speech outcomes after two-stage palate repair in adults with a non-syndromal complete unilateral cleft lip and palate (UCLP).This was a retrospective analysis of adult patients with a UCLP who underwent two-stage palate closure and were treated at our tertiary cleft centre. Patients ?17 years of age were invited for a final speech assessment. Their medical history was obtained from their medical files, and speech outcomes were assessed by a speech pathologist during the follow-up consultation.Forty-eight patients were included in the analysis, with a mean age of 21 years (standard deviation, 3.4 years). Their mean age at the time of hard and soft palate closure was 3 years and 8.0 months, respectively. In 40% of the patients, a pharyngoplasty was performed. On a 5-point intelligibility scale, 84.4% received a score of 1 or 2; meaning that their speech was intelligible. We observed a significant correlation between intelligibility scores and the incidence of articulation errors (P<0.001). In total, 36% showed mild to moderate hypernasality during the speech assessment, and 11%-17% of the patients exhibited increased nasalance scores, assessed through nasometry.The present study describes long-term speech outcomes after two-stage palatoplasty with hard palate closure at a mean age of 3 years old. We observed moderate long-term intelligibility scores, a relatively high incidence of persistent hypernasality, and a high pharyngoplasty incidence.