Steven Goudy

Conductive hearing loss and otopathology in cleft palate patients

OBJECTIVES: Assess incidence of conductive hearing loss, ear pathology, and associated communicative disorders in cleft palate patients. STUDY DESIGN: Retrospective chart review of 101 patients all treated at a tertiary facility since birth. RESULTS: The median patient age was 19 years old (range 8–25) at last follow-up, 35% female. Median age of cleft palate repair was 16 months (range 12–60). Median number of myringotomy tubes was 3 (range 1–7). Conductive hearing loss (CHL) greater than 20 db PTA was found in 25% of patients at last follow-up. Severity of CHL was mild in 75%, moderate in 21%, and severe in 4%. Cholesteatoma was identified in 5.9%. The mean age at resolution of CHL was 5 years (range 3–19). Risk factors associated with CHL at last follow-up included middle ear surgery (P = 0.016), cholesteatoma (P = 0.003), and 4 or more myringotomy tube insertions (P = 0.030). Associations between CHL and age at cleft repair, speech impairment, or learning disabilities were not found. CONCLUSIONS: Children requiring increased number of myringotomy tubes and middle ear surgery and found to have cholesteatoma are at increased risk for long-standing CHL. EBM rating: C-4 SIGNIFICANCE: Cleft palate children requiring multiple tube insertions should be monitored closely for CHL.

Neck Crepitance : Evaluation and Management of Suspected Upper Aerodigestive Tract Injury

Objective To determine safe criteria for the management of patients with crepitance of the neck.

Gli3-deficient mice exhibit cleft palate associated with abnormal tongue development

Palatogenesis depends on appropriate growth, elevation, and fusion of the palatal shelves and aberration in these processes can lead to palatal clefting. We observed a high incidence of palate clefting in mice deficient in Gli3, known for its role as a repressor in the absence of Shh signaling. In contrast with several current mouse models of cleft palate, Meckels cartilage extension, cranial neural crest migration, palatal shelf proliferation, apoptosis, and key signaling components mediated by Shh, Bmp, Fgf, and Tgfβ, appeared unaffected in Gli3−/− mice. Palatal clefting in Gli3−/− mice was consistently associated with tongue abnormalities such as failure to flatten and improper positioning, implicating a critical role of Gli3 and normal tongue morphogenesis for timely palatal shelf elevation and joining. Furthermore, Gli3−/− palatal shelves grown in roller cultures without tongue can fuse suggesting that the abnormal tongue is likely an impediment for palatal shelf joining in Gli3−/− mutants. Developmental Dynamics 237:3079–3087, 2008.

Beyond adenotonsillectomy: Outcomes of sleep endoscopy-directed treatments in pediatric obstructive sleep apnea

OBJECTIVES In this study we determine the subjective and objective outcomes of pediatric patients with refractory OSA undergoing drug-induced sleep endoscopy (DISE)-directed surgical treatment. METHODS 31 consecutive children with OSA following TA underwent DISE. 26 completed DISE-directed operative management of the level(s) of ongoing upper airway obstruction. Pre- and postoperative OSA were assessed through a detailed history (of nighttime symptoms (NS) and daytime symptoms (DS)), physical examination, and polysomnography. RESULTS Age ranged 5-18 years (mean 9.7 ± 3.4). Fourteen of 26 had trisomy 21 (51%). Operations were performed in the following frequencies: lingual tonsillectomy (LT) (22), midline posterior glossectomy (MPG) (16), revision adenoidectomy (11), inferior turbinate submucosal resection (7), uvulopalatoplasty (2), and supraglottoplasty (2). Overall, 92% reported subjective improvement. NS improved from 5.8 ± 2.9 preoperatively to 2.1 ± 2.5 postoperatively (p<0.05), while DS improved from 2.1 ± 1.3 preoperatively to 0.6 ± 1.1 postoperatively (p<0.05). Seventeen patients completed preoperative polysomnography, while only 11 of them also completed postoperative polysomnography. Mean OAHI fell from 7.0 (±5.8) events/hr to 3.6 (±1.8) events/hr (t-test, p=0.09). CONCLUSIONS Individualized, multilevel, DISE-directed operative therapy was associated with substantial improvement in subjective measures of sleep.

Secondary Alveolar Bone Grafting: Outcomes, Revisions, and New Applications

Introduction: Cleft lip and palate deformities are one of the most common birth defects. The alveolar cleft requires bony repair to allow proper eruption of dentition. The purpose of this study is to evaluate success in the repair of alveolar clefts and examine whether the addition of allogenic materials improves outcomes. Materials and Methods: One hundred three patients with cleft lip and palate were identified retrospectively after institutional review board approval was obtained. The authors reviewed their medical records, surgical complication rate, need for revision surgery, and whether allogenic materials were used. The data were then compared using analysis of variance. Results: The average patient age was 16.6 years (range, 7 to 25 years). There were 59% unilateral clefts and 41% bilateral clefts identified. The average age at palate repair was 17.5 months. The average age at alveolar bone grafting (ABG) was 8.9 years (range, 5 to 15 years). Allogenic material was used in 22 primary ABGs and 10 revision ABGs. The revision rate of unilateral ABGs was 18%, which was statistically different from the 32% revision rate of bilateral ABGs. The use of allogenic material during ABG repair did not affect the revision rate. Conclusion: Secondary alveolar bone grafting is necessary for complete rehabilitation of the cleft alveolus. The patients undergoing ABG had an overall 23% revision rate, 18% for unilateral and 32% for bilateral clefts. The use of allogenic materials during ABG did not show a statistical benefit in this study, but future review including more patients may be useful.

Tbx1 is necessary for palatal elongation and elevation.

The transcription factor TBX1 is a key mediator of developmental abnormalities associated with DiGeorge/Velocardiofacial Syndrome. Studies in mice have demonstrated that decreased dosage of Tbx1 results in defects in pharyngeal arch, cardiovascular, and craniofacial development. The role of Tbx1 in cardiac development has been intensely studied; however, its role in palatal development is poorly understood. By studying the Tbx1-/- mice we found defects during the critical points of palate elongation and elevation. The intrinsic palate defects in the Tbx1-/- mice were determined by measuring changes in palate shelf length, proliferation, apoptosis, expression of relevant growth factors, and in palate fusion assays. Tbx1-/- embryos exhibit cleft palate with failed palate elevation in 100% and abnormal palatal-oral fusions in 50%. In the Tbx1-/- mice the palate shelf length was reduced and tongue height was greater, demonstrating a physical impediment to palate elevation and apposition. In vitro palate fusion assays demonstrate that Tbx1-/- palate shelves are capable of fusion but a roller culture assay showed that the null palatal shelves were unable to elongate. Diminished hyaluronic acid production in the Tbx1-/- palate shelves may explain failed palate shelf elevation. In addition, cell proliferation and apoptosis were perturbed in Tbx1-/- palates. A sharp decrease of Fgf8 expression was detected in the Tbx1-/- palate shelves, suggesting that Fgf8 is dependent on Tbx1 in the palate. Fgf10 is also up-regulated in the Tbx1-/- palate shelves and tongue. These data demonstrate that Tbx1 is a critical transcription factor that guides palatal elongation and elevation and that Fgf8 expression in the palate is Tbx1-dependent.

Microvessel Density in Head and Neck Squamous Cell Carcinoma Primary Tumors and Its Correlation with Clinical Staging Parameters

Objective: Our objective was to assess angiogenesis in head and neck squamous cell primary tumors and measure its correlation with tumor site and clinical and pathologic staging parameters.

Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders

The popliteal pterygia syndromes are a distinct subset of the hundreds of Mendelian orofacial clefting syndromes. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. Heterozygous mutations in IRF6 cause popliteal pterygium syndrome (PPS) while homozygous mutations in RIPK4 or CHUK (IKKA) cause the more severe Bartsocas–Papas syndrome (BPS) and Cocoon syndrome, respectively. In this study, we report mutations in six pedigrees with children affected with PPS or BPS. Using a combination of Sanger and exome sequencing, we report the first case of an autosomal recessive popliteal pterygium syndrome caused by homozygous mutation of IRF6 and the first case of uniparental disomy of chromosome 21 leading to a recessive disorder. We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS‐BPS spectrum and that mutations in IKKA can cause a range of features along the BPS‐Cocoon spectrum. Our findings have clinical implications for genetic counseling of families with pterygia syndromes and further implicate IRF6, RIPK4, and CHUK (IKKA) in potentially interconnected pathways governing epidermal and craniofacial development.

Jagged1 is essential for osteoblast development during maxillary ossification

Maxillary hypoplasia occurs due to insufficient maxillary intramembranous ossification, leading to poor dental occlusion, respiratory obstruction and cosmetic deformities. Conditional deletion of Jagged1 (Jag1) in cranial neural crest (CNC) cells using Wnt1-cre; Jagged1(f/f) (Jag1CKO) led to maxillary hypoplasia characterized by intrinsic differences in bone morphology and density using μCT evaluation. Jag1CKO maxillas revealed altered collagen deposition, delayed ossification, and reduced expression of early and late determinants of osteoblast development during maxillary ossification. In vitro bone cultures on Jag1CKO mouse embryonic maxillary mesenchymal (MEMM) cells demonstrated decreased mineralization that was also associated with diminished induction of osteoblast determinants. BMP receptor expression was dysregulated in the Jag1CKO MEMM cells suggesting that these cells were unable to respond to BMP-induced differentiation. JAG1-Fc rescued in vitro mineralization and osteoblast gene expression changes. These data suggest that JAG1 signaling in CNC-derived MEMM cells is required for osteoblast development and differentiation during maxillary ossification.

Prevention of pressure ulcers after pediatric tracheotomy using a Mepilex Ag dressing

Skin irritation and ulceration beneath the tracheostomy tube or ties secondary to pressure and shearing forces on the skin frequently complicate pediatric tracheotomy in the immediate postoperative period. The aim of this study is to determine the effectiveness of Mepilex Ag dressings in reducing posttracheotomy wound complications.