RESUMEN
BACKGROUND: In patients undergoing transnasal endoscopic sellar surgery, an analysis of risk factors and predictors of intraoperative and postoperative cerebrospinal fluid leak (CSF) would provide important prognostic information. METHODS: A retrospective review of patients undergoing endoscopic sellar surgery for pituitary adenomas or craniopharyngiomas between 2002 and 2014 at 7 international centers was performed. Demographic, comorbidity, and tumor characteristics were evaluated to determine the associations between intraoperative and postoperative CSF leaks. Correlations between reconstructive and CSF diversion techniques were associated with postoperative CSF leak rates. Odds ratios (OR) were identified using a multivariate logistic regression model. RESULTS: Data were collected on 1108 pituitary adenomas and 53 craniopharyngiomas. Overall, 30.1% of patients had an intraoperative leak and 5.9% had a postoperative leak. Preoperative factors associated with increased intraoperative leaks were mild liver disease, craniopharyngioma, and extension into the anterior cranial fossa. In patients with intraoperative CSF leaks, postoperative leaks occurred in 10.3%, with a higher postoperative leak rate in craniopharyngiomas (20.8% vs 5.1% in pituitary adenomas). Once an intraoperative leak occurred, craniopharyngioma (OR = 4.255, p = 0.010) and higher body mass index (BMI) predicted postoperative leak (OR = 1.055, p = 0.010). In patients with an intraoperative leak, the use of septal flaps reduced the occurrence of postoperative leak (OR = 0.431, p = 0.027). Rigid reconstruction and CSF diversion techniques did not impact postoperative leak rates. CONCLUSION: Intraoperative CSF leaks can occur during endoscopic sellar surgery, especially in larger tumors or craniopharyngiomas. Once an intraoperative leak occurs, risk factors for postoperative leaks include craniopharyngiomas and higher BMI. Use of septal flaps decreases this risk.
Asunto(s)
Craneofaringioma/cirugía , Endoscopía/efectos adversos , Complicaciones Intraoperatorias , Neoplasias Hipofisarias/cirugía , Complicaciones Posoperatorias , Adulto , Anciano , Pérdida de Líquido Cefalorraquídeo , Craneofaringioma/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Neoplasias Hipofisarias/epidemiología , Estudios RetrospectivosRESUMEN
IMPORTANCE: Olfactory loss is a frequent symptom of patients with chronic rhinosinusitis (CRS), but our understanding of how inflammatory cytokines affect olfaction is limited. OBJECTIVES: To examine whether inflammatory cytokines are present in the olfactory cleft and whether they correlate with objective olfaction. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, patients with CRS underwent quantitative olfactory testing using the Sniffin Sticks test to calculate a composite threshold discrimination identification (TDI) score from October 21, 2013, to November 12, 2015. Nasal mucus was collected using a sponge placed in the olfactory cleft for 5 minutes, and Cytometric Bead Array was used to measure secreted immunomodulatory products. Correlations between TDI score and secreted mediators were then calculated. Data analysis was performed from October 15, 2015, to December 17, 2015. MAIN OUTCOMES AND MEASURES: Composite TDI scores and mean secreted mediator levels in mucus from the olfactory cleft. RESULTS: Thirty-four patients were enrolled (mean [SD] age, 57.3 [15.7] years; female, 21 [61.8%]; white, 26 [76.5]). The TDI scores were lower in patients with CRS with nasal polyps (CRSwNP) than in patients with CRS without nasal polyps (CRSsNP) (difference, 8.7; 95% CI, 2.5-15.0; P = .007). Interleukin (IL) 5 levels were inversely correlated with TDI scores in patients with CRSwNP and those with CRSsNP (mean [SE] ß estimate, -46.56 [15.11]; P = .005), whereas IL-6, IL-7, and vascular endothelial growth factor A were positively correlated with TDI scores only in the CRSwNP cohort. Subscale olfactory TDI scores followed similar correlations to composite TDI scores. CONCLUSIONS AND RELEVANCE: In this study, inflammatory cytokines were found in mucus collected from the olfactory cleft. Levels of IL-5, in addition to other cytokines, were associated with objective olfactory function. Further inquiry is needed to establish the source of mucous cytokines and establish whether they play a causal role in olfactory loss.
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Citocinas/metabolismo , Mucosa Nasal/metabolismo , Trastornos del Olfato/etiología , Rinitis/complicaciones , Sinusitis/complicaciones , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Olfato/metabolismoRESUMEN
BACKGROUND: Olfactory loss affects a majority of patients with chronic rhinosinusitis (CRS). Traditional objective measures of disease severity, including endoscopy scales, focus upon the paranasal sinuses and often have weak correlation to olfaction. METHODS: Adults with CRS were prospectively evaluated by blinded reviewers with a novel Olfactory Cleft Endoscopy Scale (OCES) that evaluated discharge, polyps, edema, crusting, and scarring of the olfactory cleft. Objective olfactory function was assessed using "Sniffin' Sticks" testing, including composite threshold-discrimination-identification (TDI) scores. Olfactory-specific quality of life was evaluated using the short modified version of the Questionnaire of Olfactory Disorders (QOD-NS). Interrater and intrarater reliability was assessed among 3 reviewers for OCES grading. Multivariate linear regression was then used to test associations between OCES scores and measures of olfaction, controlling for potential confounding factors. RESULTS: The OCES score was evaluated in 38 patients and had a high overall reliability (intraclass correlation coefficient [ICC] = 0.92; 95% confidence interval [CI], 0.91 to 0.96). The OCES significantly correlated with objective olfaction as measured by TDI score (p < 0.001), with TDI score falling by 1.13 points for every 1-point increase in OCES score. Similar significant associations were found for threshold, discrimination, and identification scores (p < 0.003 for all) after controlling for age, gender, race, and reviewer/review. The OCES was also highly associated with patient-reported QOD-NS scores (p = 0.009). CONCLUSION: A novel olfactory cleft endoscopy scale, OCES, shows high reliability and correlates with both objective and patient-reported olfaction in patients with CRS. Further studies to determine prognostic value and responsiveness to change are warranted.
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Trastornos del Olfato/diagnóstico , Rinitis/diagnóstico , Sinusitis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Estudios de Cohortes , Progresión de la Enfermedad , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: The goal of this study was to identify preoperative risk factors associated with increased perioperative morbidity after endoscopic pituitary surgery. METHODS: A retrospective review of patients undergoing endoscopic pituitary adenoma surgery between 2002 and 2014 at 6 international centers was performed. Standard demographic and comorbidity data, as well as information regarding tumor extent and treatment were collected. Logistic regression was used to examine risk factors for the following 30-day outcomes: systemic complications, intracranial complications, postoperative cerebrospinal fluid (CSF) leaks, length of hospital stay, readmission, and reoperation. RESULTS: Data was collected on 982 patients with a mean age of 52 years. The median body mass index (BMI) for all patients was 30.9 kg/m(2) with 56% female. The median hospital stay was 5 days and 23.8% of patients suffered a postoperative adverse event. Systemic complications occurred in 3.2% of patients and intraventricular extension was a risk factor (odds ratio [OR] 8.9). Intracranial complications occurred in 7.3% of patients and risk factors included previous radiation (OR 8.6) and intraventricular extension (OR 7.9). Reoperation occurred in 6.5% of patients and intraventricular extension (OR 7.3) and age (<40 years, OR 3.5; 40 to 64 years, OR 3.2) were risk factors. Postoperative CSF leaks occurred in 5.5% of patients and risk factors included female gender (OR 2.4), BMI ≥ 30 (OR 2.1), age (<40 years, OR 5.3; 40 to 64 years, OR, 7.9), and intraventricular extension (OR, 9.5). CONCLUSION: Postoperative endoscopic pituitary adenoma surgery complications are associated with tumors with intraventricular extension, preoperative radiation, as well as common patient comorbidities. Identification of these factors may permit implementation of strategies to reduce postoperative complications.
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Adenoma/cirugía , Cirugía Endoscópica por Orificios Naturales , Neoplasias Hipofisarias/cirugía , Complicaciones Posoperatorias/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Periodo Preoperatorio , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Fibroblasts are implicated in tissue remodeling and recruitment of inflammatory cells in chronic rhinosinusitis (CRS). Populations of fibroblasts remain unquantified in CRS subtypes. The objectives of this study were to measure fibroblast populations in subtypes of CRS, and to investigate the association between fibroblasts and disease severity. METHODS: Patients undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2011 to December 2014. Control subjects included patients undergoing endoscopic surgery for non-inflammatory conditions such as cerebrospinal fluid leak repair or non-hormone-secreting pituitary tumors. Patients completed 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires prior to surgery. Blood and tissue biopsies were taken during surgery. Percent of sinonasal fibroblasts was determined via flow cytometry by selecting fibroblast-specific protein (FSP)-positive and Mucin 1 (MUC1)-negative cells. RESULTS: A total of 69 patients were enrolled: control (n = 24), CRS without nasal polyps (CRSsNP) (n = 13), CRS with nasal polyps (CRSwNP) (n = 22), and allergic fungal rhinosinusitis (AFRS) (n = 10). Patients with CRSwNP had significantly more fibroblasts than both control (p < 0.001) and CRSsNP (p < 0.01). Patients with AFRS had the most fibroblasts when compared to control (p < 0.0001), CRSsNP (p < 0.0001), and CRSwNP (p < 0.05). Atopy and asthma were not associated with increased fibroblasts in CRSwNP (p = 0.21, p = 0.26, respectively). Increased fibroblasts correlated with subjective disease severity as measured by SNOT-22 for CRSwNP (p = 0.003) and AFRS (p = 0.048). CONCLUSION: Sinonasal fibroblasts are increased in CRSwNP and AFRS compared to control and CRSsNP. Increased fibroblasts correlated with worse quality of life in CRSwNP and AFRS.
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Fibroblastos/fisiología , Pólipos Nasales/diagnóstico , Rinitis/diagnóstico , Sinusitis/diagnóstico , Adolescente , Adulto , Anciano , Proteínas de Unión al Calcio/metabolismo , Separación Celular , Niño , Enfermedad Crónica , Progresión de la Enfermedad , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/patología , Calidad de Vida , Rinitis/patología , Proteína de Unión al Calcio S100A4 , Sinusitis/patología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: There is a lack of population-based, multi-institutional analyses of factors associated with morbidity and mortality following pituitary tumor excision. METHODS: The American College of Surgeons National Surgical Quality Improvement Project files were used to compile information on patients that had undergone transnasal microscopic pituitary tumor resection from 2006 to 2012. Patient demographics, comorbidities, operative characteristics, and morbidity and mortality in the 30 days following surgery were included. Multivariate logistic regression was used for categorical variables and multivariate linear regression was used for continuous variables to evaluate factors leading to adverse events. RESULTS: A total of 658 patients were included, of which 58 (8.81%) experienced a complication, reoperation or death in the 30 days following surgery. The most common complications were reoperation (3.37%), followed by unplanned reintubation (1.99%), urinary tract infection (1.68%), and transfusion (1.68%). Predictors of any complication, reoperation, or death include preoperative sepsis (odds ratio [OR] = 7.596) and lower preoperative serum albumin (OR = 6.667). Younger age predicted surgical complications (OR = 1.105). Predictors of medical complications include higher body mass index (OR = 1.112), chronic steroid use (OR = 6.568), preoperative sepsis (OR = 15.297), and lower preoperative serum hematocrit (OR = 1.225). Predictors of increased total length of hospital stay were older age (ß = 0.146), higher body mass index (ß = 0.188), chronic steroid use (ß = 0.142), preoperative sepsis (ß = 0.489), and lower preoperative serum albumin (ß = -0.213). CONCLUSION: Although adverse events following pituitary tumor excision are low, awareness of factors associated with morbidity and mortality in the early postoperative period may allow for improved patient monitoring and outcomes.
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Endoscopía , Senos Paranasales/cirugía , Neoplasias Hipofisarias/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/mortalidad , Neoplasias Hipofisarias/cirugía , Complicaciones Posoperatorias/mortalidad , Reoperación , Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Aspergillus fumigatus and Alternaria alternata are ubiquitous environmental fungal allergens that can exacerbate airway inflammation and contribute to the disease process in patients with chronic rhinosinusitis (CRS). These antigens have been shown to induce human sinonasal epithelial cells (HSNECs) to promote a proinflammatory response, but what is unclear is a means by which to reduce these effects. Inhaled pathogens can induce HSNECs to produce reactive oxygen species (ROS) that trigger cytokine production. OBJECTIVE: This study aimed to determine whether the free radical scavenger superoxide dismutase (SOD) could reduce HSNEC-derived inflammation, as measured by interleukin (IL)-6 and IL-8 production, in response to Aspergillus or Alternaria exposure. METHODS: Sinus tissue explants were collected at the time of surgery from control patients (n = 7) and patients with CRS with nasal polyps (CRSwNP) (n = 9). HSNECs were cultured from the explants and treated with Aspergillus, Alternaria, and SOD for 24 hours. Cell supernatants and lysates were collected, and IL-6 and IL-8 concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: In control and CRSwNP HSNECs, Aspergillus and Alternaria both increased cytokine production (p < 0.05), as measured by IL-6 and IL-8 concentration. SOD treatment reduced the inflammatory response to fungal antigen exposure from CRSwNP HSNECs but not control HSNECs. In CRSwNP patients, SOD significantly decreased IL-6 and IL-8 production after Alternaria exposure and IL-8 after Aspergillus exposure (p < 0.05). CONCLUSIONS: When HSNECs from CRSwNP patients are treated with SOD concurrently with Aspergillus or Alternaria, SOD treatment decreases the fungal antigen-induced inflammatory response. The ability to attenuate inflammation induced by common fungal allergens with SOD treatment could provide a novel therapeutic or preventative approach for patients with CRS or other allergic inflammatory airway diseases.
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Alternaria/inmunología , Antígenos Fúngicos/inmunología , Aspergillus fumigatus/inmunología , Células Epiteliales/efectos de los fármacos , Pólipos Nasales/cirugía , Senos Paranasales/patología , Rinitis/cirugía , Sinusitis/cirugía , Superóxido Dismutasa/farmacología , Células Cultivadas , Enfermedad Crónica , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Senos Paranasales/cirugíaRESUMEN
OBJECTIVES/HYPOTHESIS: To assess for the safety of intranasal steroid injections. STUDY DESIGN: Retrospective chart review and review of the medical literature. METHODS: Seventy-eight patients with chronic rhinitis or sinusitis underwent 237 intraturbinate or intrapolyp triamcinolone acetonide injections between April 2008 and June 2013 at a single, private, outpatient otolaryngology clinic. A retrospective chart review was performed to evaluate for treatment complications, symptom improvement, and demographic data. A PubMed literature search was performed for all case series extracting the incidence of visual complications following intranasal steroid injections. All published reports of visual complications from these series and independent case reports were compiled and analyzed. RESULTS: Of the 237 injections performed, 152 were intraturbinate and 85 were intrapolyp. One of the intrapolyp injections resulted in a transient visual change that resolved spontaneously. Nine other case series meeting the search criteria were found. Of the reported 117,669 injections performed, three resulted in visual complications yielding an estimated visual complication rate of 0.003%. All three of these events resolved spontaneously and resulted in no permanent visual deficits. A total of 19 reports of visual complications following intranasal steroid injections were discovered. Of these, the majority have insufficient detail regarding the injection technique or cite gross deviation from the correct injection protocol. CONCLUSION: Intranasal steroid injections are a safe treatment for chronic rhinitis and sinusitis patients. When performed correctly, there is evidence to justify the use of methylprednisolone acetate or triamcinolone acetonide injections into the inferior turbinates and nasal polyps.
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Ceguera/inducido químicamente , Glucocorticoides/efectos adversos , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Triamcinolona Acetonida/efectos adversos , Administración Intranasal , Adulto , Anciano , Anciano de 80 o más Años , Ceguera/epidemiología , Enfermedad Crónica , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Incidencia , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Estudios Retrospectivos , Rinitis/diagnóstico , Medición de Riesgo , Sinusitis/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Triamcinolona Acetonida/administración & dosificación , Adulto JovenRESUMEN
OBJECTIVES/HYPOTHESIS: When combined with local sphenopalatine (SP) injection and moderate hypotension, transoral or transcutaneous local injection of the anterior palatine (AP) vessels reduces intraoperative bleeding in hereditary hemorrhagic telangiectasia (HHT) patients undergoing nasal surgery. STUDY DESIGN: Retrospective chart review of 55 consecutive HHT patients undergoing a bevacizumab injection for recalcitrant epistaxis. Nineteen patients received local injections to only the SP vasculature, and 36 patients received AP and SP injections. METHODS: Main outcome variable was estimated blood loss during nasal surgery. Independent variables included sex, age, epistaxis severity score, surgical techniques (including laser), and blood pressure parameters (baseline, preinduction, and postintubation). RESULTS: The mean blood loss in HHT patients receiving SP injections alone was 111 mL, whereas it was 22 mL for those receiving both AP + SP injections. This difference between groups approached statistical significance (P = .075). Blood pressure parameters were similar in both groups with no appreciable difference between intraoperative systolic and mean arterial blood pressure. CONCLUSIONS: The addition of either sublabial or transcutaneous AP injection to the standard SP block markedly reduces blood loss in HHT epistaxis nasal surgery.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Pérdida de Sangre Quirúrgica/prevención & control , Epistaxis/etiología , Epistaxis/prevención & control , Procedimientos Quírurgicos Nasales , Telangiectasia Hemorrágica Hereditaria/complicaciones , Bevacizumab , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Hueso Paladar , Estudios RetrospectivosRESUMEN
OBJECTIVE/HYPOTHESIS: Bevacizumab delivered as a submucosal and topical intranasal therapy effectively controls hereditary hemorrhagic telangiectasia (HHT)-associated epistaxis. STUDY DESIGN: Prospective institutional review board-approved study. METHODS: Between December 2009 and December 2010, 19 patients with HHT-associated epistaxis were treated with 100 mg of intranasal submucosal bevacizumab. Following treatment, patients were contacted monthly to report their epistaxis severity score (ESS) for 9 or more months after their initial treatment. If a patient had a significant increase in their ESS, they were offered treatment with 100 mg of topical bevacizumab, administered via a metered dose atomizer. All treatments were recorded. RESULTS: All 19 patients had a postinjection ESS documented through 9 months, whereas 17 patients had completed ESS data between months 10 and 12. Six of the 19 patients received eight additional 100 mg of topical bevacizumab treatments because they had an increase in their ESS. Results demonstrated a mean preinjection ESS of 8.12, with an ESS nadir of 2.00 reached at 2 months following submucosal injection (P < 0.0001). Over the following 12 months, the mean ESS steadily increased back to a maximum of 3.6 reached at 11 months following injection (P < .0001). CONCLUSIONS: Intranasal submucosal bevacizumab effectively treats HHT-associated epistaxis for up to 12 months following treatment.
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Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Administración Intranasal , Adulto , Anciano , Anciano de 80 o más Años , Bevacizumab , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Mucosa Nasal , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Resultado del Tratamiento , Factor A de Crecimiento Endotelial VascularRESUMEN
OBJECTIVES/ HYPOTHESIS: Intranasal Bevacizumab is an effective therapy for epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: Retrospective chart review. METHODS: In 32 successive patients presenting with recurrent HHT epistaxis 25-100 mg of Bevacizumab was applied intranasally either as a submucosal injection or as a topical spray between November 2008 and May 2010. In many of the injected patients, the Potassium Titanyl Phosphate (KTP) laser was used adjunctively for vessel photocoagulation. A phone interview was performed in July 2010 to assess for treatment efficacy. RESULTS: All 32 treated patients were contacted with pre- and posttreatment epistaxis severity scores (ESS) compared. Seventeen patients received topical Bevacizumab, 10 patients received a submucosal injection, and 5 patients received both. In addition, 12 patients were also treated with the KTP laser at the time of their submucosal injection. In the pretreatment period the average ESS was 7.0 (SD = 2.1), whereas in the posttreatment group the average ESS was 2.9 (SD = 1.7). This represents a significant improvement in epistaxis severity (P < .0001). CONCLUSIONS: In HHT patients intranasal Bevacizumab, applied as a topical spray or a submucosal injection, significantly improves epistaxis as measured by the Epistaxis Severity Score.
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Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Epistaxis/tratamiento farmacológico , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Administración Intranasal , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados , Bevacizumab , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inyecciones , Coagulación con Láser , Láseres de Estado Sólido/uso terapéutico , Masculino , Persona de Mediana Edad , Mucosa Nasal/efectos de los fármacos , Rociadores Nasales , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES/HYPOTHESIS: Interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome (VWS), is a candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) because a number of studies have supported an association between NSCLP and single nucleotide polymorphisms (SNPs) in IRF6 in several populations. This project investigated the contribution of IRF6 to NSCLP in the Honduran population, a previously unstudied group with a high prevalence of NSCLP. STUDY DESIGN: Family-based joint linkage and association study. METHODS: A set of five SNPs in and around IRF6 previously reported to be associated with NSCLP were tested for association with NSCLP in 276 affected and unaffected Honduran individuals from 59 families with at least two members affected by clefting and at least one member with confirmed NSCLP. RESULTS: We observed support of linkage for three SNPs-rs1856161, rs2235371, and rs2235377-under a dominant model (log of odds [LODs] = 1.97, 1.56, 1.73, respectively). Subsequent single-point, haplotype, and joint linkage and association analyses continued to support the association with NSCLP (P < or = .05) at these three SNPs. When analysis was restricted to NSCLP cases, excluding cleft palate only cases, support for association strengthened. CONCLUSIONS: This is the first study to demonstrate that three candidate SNPs within IRF6 are significantly associated with NSCLP in the Honduran population, providing the first genetic clue to NSCLP observed in the Honduran population and confirming findings from populations in other parts of the world. Further studies are needed to identify the putative variant(s).