J. Fredrik Grimmer

Laser eustachian tuboplasty: two-year results.

Objective/Hypothesis: Laser eustachian tuboplasty (LETP) combined with appropriate medical management will eliminate the chronic presence of middle ear effusions in selected patients.

Sleep Disordered Breathing and Obstructive Sleep Apnea in the Cleft Population

Objectives/Hypothesis: Children with cleft deformities have the tendency for multilevel airway obstruction. The incidence of sleep disordered breathing (SDB) in this population has not been well studied. This study attempts to describe the high incidence and the results of intervention.

Update on eustachian tube dysfunction and the patulous eustachian tube

The purpose of this review is to summarize the recent knowledge on eustachian tube dysfunction and the patulous eustachian tube. Recent findingsA clinically useful test for eustachian tube function is still lacking. Narrowing of the isthmus alone was demonstrated to be an insufficient cause of otitis media. Inflammatory mediators identified within the eustachian tube and middle ear cells were causally linked with otitis media with effusion. Increasing evidence was found that allergic disease and reflux may be two of the most important contributors of tubal inflammation causing otitis media with effusion. The adenoid size and proximity to the torus tubaris may also be important in considering which patients with persistent otitis media with effusion may benefit from adenoidectomy. Computed tomography scan has documented loss of soft tissue within the cartilaginous eustachian tube in patients with patulous eustachian tubes. An endoscopic approach to seal the tubal lumen has been found to be effective in relieving patulous symptoms. SummaryThese studies suggest that allergic rhinitis and gastroesophageal reflux should be investigated in patients with eustachian tube dysfunction. Adenoidectomy should also be considered in patients who have adenoids that obstruct the torus tubaris. Patients with a patulous eustachian tube may benefit from an endoscopic closure. Further research is needed to identify a clinically useful test for eustachian tube dysfunction.

RASA1 analysis: clinical and molecular findings in a series of consecutive cases.

RASA1 mutations have been reported to be associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM), arteriovenous fistulas (AVF), or Parkes Weber syndrome. But the number of cases with RASA1 mutations reported to date is relatively small and the spectrum of phenotypes caused by mutations in this gene is not well defined. Mutation results and clinical findings in thirty-five unrelated consecutive cases sent for RASA1 molecular sequencing testing at ARUP Laboratories within the last two years were evaluated. Eight individuals had a pathogenic RASA1 mutation of which six were novel. These eight individuals all had CMs (seven had multifocal CMs; one had multiple CMs), and six also had a brain or facial AVM. Two individuals with multifocal CMs including one with a fast flow lesion had a variant of uncertain significance. All other individuals, including sixteen with CMs and one with a vein of Galen aneurysm, tested negative for a RASA1 mutation. Our data suggest that multifocal CM is the key clinical finding to suggest a RASA1 mutation. The clinical diagnostic mutation detection rate among all samples sent for RASA1 testing was 29% (10/35) which increases to approximately 39% (10/26) if patients without CMs are excluded.

Propranolol use for infantile hemangiomas: American Society of Pediatric Otolaryngology Vascular Anomalies Task Force practice patterns.

IMPORTANCE This study provides multi-institutional practice guidelines for the initiation of propranolol hydrochloride treatment of routine infantile hemangiomas. OBJECTIVE To provide information on current propranolol treatment practices for infantile hemangiomas among a cohort of pediatric otolaryngologists. DESIGN AND SETTING A survey for initiation of propranolol therapy was created by the American Society of Pediatric Otolaryngology Vascular Anomalies Task Force Subcommittee. After an initial pilot of the survey by 4 task force members, the survey was modified and then distributed by e-mail. Results were transferred to spreadsheet format and analyzed. PARTICIPANTS All 51 members of the task force. RESULTS A total of 18 respondents from 15 institutions submitted completed surveys. Data from respondents at the same institution were aggregated and/or averaged to minimize regional bias. Fourteen of 15 responding institutions (93%) treat patients with infantile hemangioma as part of a multidisciplinary vascular anomalies team. Ten institutions (67%) routinely consult cardiology before initiation of propranolol therapy. The median propranolol hydrochloride initiation dosage is 2.00 (mean [SD], 1.65 [0.64]; range, 0.45-2.50) mg/kg/d. Postinitiation monitoring for propranolol therapy includes blood pressure (15 of 15 respondents [100%]), serum glucose levels (7 of 15 [47%]), and pulse oximetry (2 of 15 [13%]). Only 2 institutions routinely admit all patients for initiation of propranolol therapy. Typical duration of therapy ranges from 4 to 8 (5 of 15 [33%]) or 8 to 12 months (10 of 15 [67%]), and cessation of therapy in most cases is based on the clinical response (7 of 14 [50%]) or the age of the patient (6 of 14 [43%]). CONCLUSIONS AND RELEVANCE Propranolol is a commonly used medication for the treatment of infantile hemangiomas among otolaryngologists in the Vascular Anomalies Task Force. Propranolol therapy is commonly initiated in the outpatient setting and continued for as long as 12 months.

Standardized Outcome and Reporting Measures in Pediatric Head and Neck Lymphatic Malformations

Objective To develop general and site-specific treatment effect and outcome measures to standardize the reporting of head and neck lymphatic malformation (HNLM) treatments. Study Design Consensus statement/expert opinion. Setting Multiple tertiary academic institutions. Subjects and Methods The modified Delphi method is an iterative process of collecting expert opinions, refining opinions through discussion and feedback, statistically aggregating opinions, and using these aggregates to generate consensus opinion in the absence of other data. The modified Delphi method was used by a multi-institutional group of otolaryngology and interventional radiology experts in the field of vascular anomalies to formulate a list of recommended reporting outcomes for the study and treatment of head and neck lymphatic malformations. Results Through 3 rounds of iteration, 10 expert panelists refined 98 proposed outcome measures and 9 outcome categories to a final consensus set of 50 recommended outcome measures in 3 global categories (general, demographics, and treatment complications) and 5 site-specific categories (orbit, oral cavity, pharynx, larynx, and neck). Conclusions We propose the first consensus set of standardized reporting measures for clinical and treatment outcomes in studies of HNLMs. Consistent outcome measures across future studies will facilitate comparison of treatment options and allow systematic review. We hope that these guidelines facilitate the design and reporting of subsequent HNLM studies.

Candidate Locus Analysis for PHACE Syndrome

PHACE syndrome (OMIM #606519) is a neurocutaneous syndrome of unknown etiology and pathogenesis. We report on an individual with PHACE syndrome with a complete deletion of SLC35B4 on 7q33. In order to further analyze this region, SLC35B4 was sequenced for 33 individuals with PHACE syndrome and one parental set. Common polymorphisms with a possible haplotype but no disease causing mutation were identified. Sixteen of 33 samples of the PHACE syndrome patients were also analyzed for copy number variations using high‐resolution oligo‐comparative genomic hybridization (CGH) microarray. A second individual in this cohort had a 26.5 kb deletion approximately 80 kb upstream of SLC35B4 with partial deletion of the AKR1B1 on 7q33. The deletions observed on 7q33 are not likely the singular cause of PHACE syndrome; however, it is possible that this region provides a genetic susceptibility to phenotypic expression with other confounding genetic or environmental factors.

Cochlear abnormalities associated with enlarged vestibular aqueduct anomaly

OBJECTIVES The objective of this study is to examine the correlation between enlarged vestibular aqueduct (EVA) anomaly and other inner ear anomalies such as cochlear dysplasia, vestibulocochlear dysplasia and modiolar hypoplasia. METHODS Retrospective chart review, with institutional review board approval, of patients with EVA who received treatment at Primary Childrens Medical Center or University Hospital at the University of Utah, between 1997 and 2006. Review of radiographs was done to evaluate for the presence of EVA and other inner ear anomalies. RESULTS Twenty patients (40 ears) were included in the study, 17 patients had bilateral EVA and three patients had unilateral EVA. There were 10 females and 10 males. The average age of all patients at the time of initial diagnosis was 1.7 years (0-6 years). Thirty-seven ears were shown to have EVA (92.5%). Of those ears with EVA, 29 (78.4%) had one or more inner ear anomalies. Twenty-three (62.2%) ears had cochlear dysplasia, six (16.2%) had vestibulocochlear dysplasia, and 18 (48.7%) had modiolar hypoplasia. CONCLUSIONS Using small field of view, thin section CT and/or MR imaging, cochleovestibular abnormalities are commonly identified in association with EVA.

Genetic Variants Associated with Port-Wine Stains

Background Port-wine stains (PWS) are capillary malformations, typically located in the dermis of the head and neck, affecting 0.3% of the population. Current theories suggest that port-wine stains are caused by somatic mutations that disrupt vascular development. Objectives Understanding PWS genetic determinants could provide insight into new treatments. Methods Our study used a custom next generation sequencing (NGS) panel and digital polymerase chain reaction to investigate genetic variants in 12 individuals with isolated port-wine stains. Importantly, affected and healthy skin tissue from the same individual were compared. A subtractive correction method was developed to eliminate background noise from NGS data. This allowed the detection of a very low level of mosaicism. Results A novel somatic variant GNAQ, c.547C>G, p.Arg183Gly was found in one case with 4% allele frequency. The previously reported GNAQ c.548G>A, p.Arg183Gln was confirmed in 9 of 12 cases with an allele frequency ranging from 1.73 to 7.42%. Digital polymerase chain reaction confirmed novel variants detected by next generation sequencing. Two novel somatic variants were also found in RASA1, although neither was predicted to be deleterious. Conclusions This is the second largest study on isolated, non-syndromic PWS. Our data suggest that GNAQ is the main genetic determinant in this condition. Moreover, isolated port-wine stains are distinct from capillary malformations seen in RASA1 disorders, which will be helpful in clinical evaluation.

The effect of age on pediatric tympanoplasty outcomes: A comparison of preschool and older children

OBJECTIVES Determine whether the outcome of tympanoplasty in preschool children is different from that of older children. STUDY DESIGN Retrospective case series. METHODS Retrospective review of children having undergone a primary tympanoplasty by 4 surgeons for a tympanic membrane perforation between 2002 and 2013. RESULTS Data from 50 children age 2-4, 130 children age 5-7 and 105 children age 8-13 years old were reviewed. Median follow-up was 7.5 months. On crude analysis, the incidence of anatomical success was not significantly different between the different age groups (p=0.38), the success rate was respectively 69.4%, 68.5% and 79.1% with an overall rate of 72.5%. 5.9% of all children required later insertion of tympanostomy tubes, 10.2% in preschool children. The post-operative audiology results were similar for all groups with a mean improvement of 9dB in the air-bone gap. When limiting the analysis to the 155 children having at least 6 months of follow-up, the rate of success was respectively 50.0%, 60.8% and 74.0% (p=0.10). After multivariate analysis controlling for the effect of surgeon, approach and etiology, the odds ratio of perforation was respectively 5.48, 2.27 and 1.00 for the different age groups. CONCLUSION Children younger than 4 years of age have the worst outcome after tympanoplasty. It remains uncertain whether the benefits of hearing improvement and quality of life may outweigh that of a high rate of a residual, usually smaller, perforation. Prospective studies are needed to confirm these results and delineate the patient characteristics and technique most likely to lead to successful results.