Biomedical subjects

Margaret Kenna

Publications and source records attributed to Margaret Kenna.

6 recordsLinked to original sources

PubMed2025

ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time.

PURPOSE: The Clinical Genome Resource (ClinGen) Hearing Loss Gene Curation Expert Panel was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen's semiquantitative framework. ClinGen mandates the timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong every 2 to 3 years. METHODS: Thirty-five GDRs met the criteria for recuration within 2 years of original curation. Previous evidence was reevaluated using the latest curation guidelines, and a comprehensive literature review was performed to obtain new evidence. Recurations were approved by the Gene Curation Expert Panel and published on the ClinGen website (www.clinicalgenome.org). RESULTS: Eight of 35 GDRs (22%) changed their classification. Two Moderate and 5 Strong GDRs were upgraded to Definitive because of new case evidence. One Strong was subsumed under another Definitive GDR after evaluation of the lumping/splitting of disease entities. Twenty-seven of 35 patients remained unchanged, with little to no new evidence reported. CONCLUSION: Genes classified as Moderate and Strong were likely to build evidence and change their classification over time, whereas Limited were unlikely to gain evidence. These findings highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most recent evidence into their efforts.

Humans↗

PubMed2006

Pediatric adenoidectomy: what is the effect of obstructive symptoms on the likelihood of future surgery?

OBJECTIVE: Determine if pediatric patients undergoing adenoidectomy for obstruction have an increased likelihood of undergoing eventual tonsillectomy and/or second adenoidectomy over extended follow-up. METHODS: Retrospective cohort study within the ambulatory surgery component of a tertiary children's hospital. Exclusion criteria consisted of the presence of significant co-morbid conditions (obesity, craniofacial syndrome, cerebral palsy, etc.) and less than 1 year of post-adenoidectomy follow-up. The study population included 100 children (mean age=3.9 years, range 0.9-15 years) randomly selected from a financial billing database undergoing adenoidectomy either with pre-operative obstructive symptoms (OB n=52) or without pre-operative obstructive symptoms (NOB n=48) with a minimum of 1 year of retrospective follow-up. Electronic records were searched for subsequent surgery (tonsillectomy and/or revision adenoidectomy). RESULTS: Overall, 29 of 100 children (29%) underwent subsequent surgery (tonsillectomy and/or revision adenoidectomy) over an average of 3.46 years (range 1.0-6.59 years) retrospective follow-up. Children in the OB group were three times more likely (age, sex adjusted odds ratio=3.03, 95% confidence interval =1.18-7.78 p=0.021) than children in the NOB group to require tonsillectomy or second adenoidectomy. Age less than 2 years at time of initial adenoidectomy also suggested an increased likelihood of subsequent surgery. CONCLUSION: Children undergoing adenoidectomy with obstructive symptoms are more likely to require eventual tonsillectomy and/or second adenoidectomy than those undergoing adenoidectomy without obstruction. However, the low absolute likelihood of future surgery precludes a generalized recommendation for tonsillectomy in these children.

Adenoidectomy↗

PubMed2005

The use of perioperative antibiotics in tonsillectomy: does it decrease morbidity?

OBJECTIVE: To assess the efficacy of perioperative antibiotics in decreasing post-operative morbidity among patients undergoing tonsillectomy or adenotonsillectomy. DESIGN: Meta-analysis based on a structured search of the literature, using MEDLINE and the Cochrane database. SUBJECTS: Only articles, which included both treatment and control groups, were included in the final analysis. Studies were limited to ones that involved human subjects, including both children and adults. Studies using steroids and topical antibiotics were excluded. OUTCOMES: Articles were abstracted for patient factors, elements of study design, methods of patient assignment to treatment and control groups, and clinical outcomes. The primary outcome, time required for return to normal oral intake, was analyzed in the final meta-analysis. METHODS: Four hundred and twenty-eight articles were initially identified. There were 23 potentially appropriate articles. Of these, 18 were able to be located in full text form and in English. Seven of these studies directly studied the efficacy of perioperative antibiotics (versus no antibiotics) in decreasing post-operative morbidity. Four studies had sufficient information to calculate effects estimates (xi) and standard deviations (Si) for the primary outcome. Three studies either did not report the outcome of interest or did not report a measure of stability (e.g. p-value or confidence interval). The data available from the first four studies were combined in a quantitative meta-analysis. Statistical analyses were performed using STATA for Windows software. RESULTS: The pooled estimate indicated that the antibiotic group returned to normal oral intake, on average, 1 day sooner than the controls. This difference was found to be statistically significant with a 95% confidence interval of 0.5-1.6 days. An additional assessment of three qualitative reports also suggested the use of perioperative antibiotics for adenotonsillectomy was associated with less post-operative pain. However, studies varied in terms of study quality, sample size, outcome examined, measure used and antibiotic administered. Definitive conclusions regarding the effect of perioperative antibiotics on other outcomes including bleeding, halitosis, fever, activity level and nausea and vomiting could not be drawn due to the small numbers of studies. CONCLUSIONS: In this meta-analysis, the use of perioperative antibiotics in patients who have had tonsillectomy or adenotonsillectomy appears to be associated with a 1-day reduction in the time required for return to normal oral intake. For other potentially important outcomes, such as post operative pain or bleeding, sufficient data were not available to make any definitive conclusions regarding the effect of perioperative antibiotics.

Adolescent↗

PubMed2005

Pediatric facial nerve paralysis: patients, management and outcomes.

OBJECTIVE: To characterize the causes and treatment of facial nerve paresis (FNP) in pediatric patients. METHOD: Retrospective study in a tertiary care pediatric hospital. Thirty-four patients identified with partial or complete FNP evaluated between 1997 and 2003. A review of the medical records including sex, age, laterality, etiology, therapy, severity of paralysis according to House-Brackman (HB) six-point grading scale, duration, and degree of recovery. RESULTS: Thirty-five cases of FNP. Causes of FNP were infectious (13), traumatic (7), iatrogenic (5), congenital (4), Bell's/Idiopathic (3), relapsing (2) and neoplastic (1). Peak age distributions for both infectious and traumatic etiologies were bimodal: 1-3 and 8-12 years. Of the 13 infectious cases, 11 were associated with acute otitis media with effusion (AOME). Four (4/11) were bacterial-culture negative. Seven (7/11) were bacterial-culture positive, four (4/7) of which required prolonged, broth-medium culture. Bacteria cultured predominantly included Staphylococcus non-aureus species (5/7) and Propionobacterium acnes (3/7). One (1/13) was viral culture positive (Herpes Simplex Virus). All six patients who received intravenous steroids for OME-associated FNP received the doses within the first week of presentation and had complete recovery (HB I/VI); three of five patients who did not receive steroids had complete recovery. There were five iatrogenic cases; two (2/5) were planned surgical sacrifices and three (3/5) were complications of middle ear/mastoid surgery. Facial nerve function associated with infection returned in 0.5-2 months while, when associated with trauma, returned in 0.25-30 months. CONCLUSIONS: In infectious or traumatic FNP, children aged 1-3 and 8-12 years are the primary groups involved. In AOME FNP, culture-identified organisms may not be representative of traditional pathogens. Infectious FNP averaged 1 month for recovery while traumatic FNP averaged 9 months. Intravenous steroid therapy may improve the outcome. Recovery was complete (HB I/VI) in 8/10 infectious and 4/6 traumatic cases.

Adolescent↗

PubMed2003

Use of a multiplex PCR/sequencing strategy to detect both connexin 30 (GJB6) 342 kb deletion and connexin 26 (GJB2) mutations in cases of childhood deafness.

Hearing loss is a common congenital disorder that is frequently associated with mutations in the Cx26 gene (GJB2). Three recent reports that found a large deletion in another DFNB1 gene, Cx30 (GJB6), suggest that this defect may cause nonsyndromic recessive hearing loss through either a homozygous deletion of Cx30, or digenic inheritance of a Cx30 deletion and a Cx26 mutation in trans. We designed a simple diagnostic strategy with multiplex PCR followed by direct sequencing to allow for the simultaneous detection of Cx26 mutations and Cx30 deletions, and evaluated its effectiveness as a clinical genetic test by examining 200 DNA samples. In the 108 samples from deaf subjects, two digenic mutations were identified in Cx26 and Cx30 (E47X/342 kb deletion and 167delT/342 kb deletion); 69 had only Cx26 mutations (29 biallelic, 40 singleton), including two novel frameshift mutations 511-512insAACG and 358-360delAG; and 37 had no detectable mutation in either Cx26 or Cx30. Our deletion mapping suggested that the proximal breakpoint of all reported Cx30 large deletions are between the nucleotide 444 and 627 at the Cx30 coding region within a maximal interval of 78 or 184 bp. This simultaneous examination of Cx26 and Cx30 is a practical and efficient diagnostic approach for patients with nonsyndromic congenital deafness.

Base Sequence↗

PubMedDate not supplied

Effectiveness of sequencing connexin 26 (GJB2) in cases of familial or sporadic childhood deafness referred for molecular diagnostic testing.

PURPOSE: Hearing loss is a common congenital disorder that is frequently associated with mutations in the GJB2 gene encoding the connexin 26 protein (Cx26). We sought to evaluate the effectiveness of direct DNA sequencing for detection of Cx26 mutations as a clinical diagnostic test. METHODS: We designed a clinical assay using a three-step polymerase chain reaction (PCR)-based DNA sequencing strategy to detect all possible mutations in the open reading frame and flanking sequences of Cx26. The results of the first 324 cases of childhood deafness referred for diagnostic testing were analyzed. RESULTS: A total of 127 of the 324 (39.2%) cases had at least one mutant Cx26 allele (36.1% of sporadic cases, 70% of familial cases). Of these 127 case, 57 (44.8%) were homozygotes or compound heterozygotes. Thirty-four different mutations were identified, including 10 novel mutations, 6 of which (T8M, K15T, R32L, M93I, N206S, and 511-512insAACG) may be pathogenic. We also provide new evidence on the pathogenicity or nonpathogenicity of 12 previously reported mutations, and clarify the confusing nomenclature of the 313-326del14 mutation. CONCLUSION: A simple and rigorous method for efficient PCR-based sequence analysis of Cx26 is a sensitive clinical assay for evaluating deaf children. Its widespread use is likely to identify additional pathogenic mutations and lead to a better understanding of the clinical significance of previously identified mutations.

Alleles↗