Charlotte Chiong - Academia.edu (original) (raw)

Conference Presentations by Charlotte Chiong

Research paper thumbnail of THE ELECTRICALLY ELICITED STAPEDIUS REFLEX THRESHOLD AS AN ESTIMATE OF MAXIMUM COMFORT LEVEL IN MedEl COMBI 40 and COMBI 40+ IMPLANTs IN THE PHILIPPINES

THE ELECTRICALLY ELICITED STAPEDIUS REFLEX THRESHOLD AS AN ESTIMATE OF MAXIMUM COMFORT LEVEL IN MedEl COMBI 40 and COMBI 40+ IMPLANTs IN THE PHILIPPINES, 2000

The electrically stimulated middle ear muscle reflex (eSRT) threshold was examined as an estimate... more The electrically stimulated middle ear muscle reflex (eSRT) threshold was examined as an estimate of maximum comfort levels (MCLs) in Med-El Combi 40 and Combi 40+ implant clients in the Philippines. These objective MCLs were compared with the previous behaviourally obtained (subjective) MCLs. There was a moderate positive correlation between the subjective and objective maps. The correlation tended to be stronger for older children and those who had been seen for a greater number of mapping sessions. There was a clear trend showing that as the number of mapping sessions increased, the subjective MCL’s approached the eSRT. For this reason, the eSRT thresholds are considered to be a good first estimate of the true MCLs especially in young children who may have no clear concept of „loudness“ due to both age and lack of experience with auditory input. The eSRT remained stable (low variance) from trial to trial. For practical reasons, it is also recommended that the subjective/observational technique for mapping not be abandoned since some children may not demonstrate a clear eSRT for a variety of reasons. This paper also includes a discussion of various issues that arose during the study which provide both food for thought and a potential basis for further research.

Key words: MCL Maximum Comfort Levels, Stapedius Reflex, Cochlear Implants, Mapping, Dynamic Range, Pediatric Audiology

Papers by Charlotte Chiong

Research paper thumbnail of Auditory Brainstem Implantation Improves Speech Recognition in Neurofibromatosis Type II Patients

Acoustic neuroma · Auditory brainstem implant · Nonauditory side effects · Open-set sentence reco... more Acoustic neuroma · Auditory brainstem implant · Nonauditory side effects · Open-set sentence recognition · Subjective benefits · Vestibular schwannoma This prospective study aimed to determine speech understanding in neurofibromatosis type II (NF2) patients following implantation of a MED-EL COMBI 40+ auditory brainstem implant (ABI). Patients (n = 32) were enrolled postsurgically. Nonauditory side effects were evaluated at fitting and audiological performance was determined using the Sound Effects Recognition Test (SERT), Monosyllable-Trochee-Polysyllable (MTP) test and open-set sentence tests. Sub-jective benefits were determined by questionnaire. ABI activation was documented in 27 pa-tients, 2 patients were too ill for testing and 3 patients were without any auditory perception. SERT and MTP outcomes under auditory-only conditions improved significantly between first fitting and 12-month follow-up. Open-set sentence recognition improved from 5 % at first fit-ting to 37 % after 1...

Research paper thumbnail of Agreement between Human Voice (“Baah”) Test and Otoacoustic Emissions in Screening of Infants for Binaural Hearing Loss

Research paper thumbnail of Agreement between Human Voice (“Baah”) Test and Otoacoustic Emissions in Screening of Infants for Binaural Hearing Loss

Presented at the 16th ASEAN ORL-HNS Congress, November 11, 2015, The Empress Convention Center, C... more Presented at the 16th ASEAN ORL-HNS Congress, November 11, 2015, The Empress Convention Center, Chiang Mai, Thailand, through an educational grant of ADP Pharma Corporation, and as a poster presentation at the 18th Anniversary of the National Institutes of Health, 14th UP Manila Science and Technology Week, and at the 7th Anniversary of the Metro Manila Research and Development Consortium, February 17-18, 2016, SMX Convention Center, Mall of Asia.

Research paper thumbnail of The Cost-Effectiveness and Budget Impact of a Community-based Universal Newborn Hearing Screening Program in the Philippines

Research paper thumbnail of The SLC26A4 c.706C>G (p.Leu236Val) Variant is a Frequent Cause of Hearing Impairment in Filipino Cochlear Implantees

Otology & Neurotology

HYPOTHESIS Variants in SLC26A4 are an important cause of congenital hearing impairment in the Phi... more HYPOTHESIS Variants in SLC26A4 are an important cause of congenital hearing impairment in the Philippines. BACKGROUND Cochlear implantation is a standard rehabilitation option for congenital hearing impairment worldwide, but places a huge cost burden in lower-income countries. The study of risk factors such as genetic variants that may help determine genetic etiology of hearing loss and also predict cochlear implant outcomes is therefore beneficial. METHODS DNA samples from 29 GJB2-negative Filipino cochlear implantees were Sanger-sequenced for the coding exons of SLC26A4. Exome sequencing was performed to confirm results. RESULTS Four cochlear implantees with bilaterally enlarged vestibular aqueducts (EVA) were homozygous for the pathogenic SLC26A4 c.706C>G (p.Leu236Val) variant, which has a minor allele frequency of 0.0015 in Filipino controls. In patients with the SLC26A4 variant there was no association between cochlear implant outcome and age at implantation or duration of implant. There was also no association between the occurrence of the SLC26A4 variant and postsurgical audiometric thresholds and parents' evaluation of aural/oral performance of children (PEACH) scores. On the other hand, the SLC26A4 variant increased presurgical median audiometric thresholds (p = 0.01), particularly at 500 to 2000 Hz. CONCLUSION The SLC26A4 c.706C>G (p.Leu236Val) variant is a frequent cause of congenital hearing impairment in Filipinos and is associated with bilateral EVA and increased presurgical audiometric thresholds, but does not adversely affect post-implant outcomes.

Research paper thumbnail of Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants

Journal of Medical Genetics

BackgroundOtitis media (OM) susceptibility has significant heritability; however, the role of rar... more BackgroundOtitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.MethodsWe performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues.ResultsA large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the oute...

Research paper thumbnail of In Reply to the Letter to the Editor regarding “Temporal Bone Chondroblastoma: Systematic Review of Clinical Features and Outcomes”

Research paper thumbnail of Cost-Analysis of Universal Newborn Hearing Screening in the Philippines

Research paper thumbnail of Auditory Brainstem Response Latencies of Infants and Maternal Exposure to Environmental Toxic Products

Research paper thumbnail of Baseline Knowledge, Attitudes, and Practices of Healthcare Practitioners in Rizal Province, Philippines toward Implementing the Universal Newborn Hearing Screening Program

Acta Medica Philippina

Objective. The study describes the current knowledge, attitudes, and practices of healthcare prac... more Objective. The study describes the current knowledge, attitudes, and practices of healthcare practitioners in Rizal province regarding the implementation of the universal newborn hearing screening program (UNHSP).Materials and Methods. A descriptive phenomenologic research design through focus group discussions with pediatric and OBGYN consultants in a government hospital, nurses from private primary and secondary hospitals, midwives from private birthing homes, and rural health workers.Results. Attitudes. All participants recognized that they had important roles in implementing the program except the OBGYN consultants as they felt that information about the UNHSP should be provided by pediatricians. Practices. The lack of a screening device, trained personnel, and a referral network were the most common barriers in implementing the program. Knowledge. Most participants lacked specific knowledge about hearing loss and its implications in the UNHSP.Conclusion. Most participants were ...

Research paper thumbnail of A Chronicle of Change: the Core Values We Cherish

Philippine Journal of Otolaryngology Head and Neck Surgery

As we approach the last quarter of the year, it is time that Fellows of the Philippine Society of... more As we approach the last quarter of the year, it is time that Fellows of the Philippine Society of Otolaryngology-Head and Neck Surgery (PSOHNS) receive this report from the President and the Board of Trustees. Following the successful staging of the midyear congress at EDSA Shangrila and distribution of the coffeetable book-- another chronicle of our rich history-- we also witnessed the launching of the advocacy campaign “Change is in the Air” led by Philippine Academy of Rhinology (PAR) Chair Dr. Tony Chua with Drs. Mari Enecilla and Joel Romuladez that even saw print in the newspapers. Despite the challenges, the support we received from our pharmaceutical friends was tremendous and the avowed fund support for advocacy from the proceeds of that congress amounting to a little over P2 million will certainly go a long way for our future campaigns. Our new home and headquarters at 27 Manga Road, Quezon City was finally inaugurated last July 8. Legal ownership with the title of the pro...

Research paper thumbnail of President’s inaugural address Philippine Society of Otolargyngology head and neck Surgery annual Congress December 2, 2015

Philippine Journal of Otolaryngology Head and Neck Surgery

Past Presidents of the PSO-HNS especially founding President Dr. Tierry Garcia, President of the ... more Past Presidents of the PSO-HNS especially founding President Dr. Tierry Garcia, President of the PBO-HNS Dr. Rudy Nonato, Presidents of the chapters and Chairs of the subspecialty groups, co-Fellows of the society, friends, guests, ladies and gentlemen. At the threshold of the 60th anniversary of this venerable society, I stand here today as the humble recipient of your trust and confidence as your President. As a child I have seen the photos of the heroic founders and had been witness to the lasting friendship between them. I was in high school when my father, Dr. Armando T. Chiong, Sr. became the 10th President of the organization. I now follow my brother, President Dr. Armando Chiong, Jr. to continue the programs he started. Such laudable programs started by the past years’ BOT with the advocacy map, public awareness, chapter and institutional initiatives will be continued. With the funding earmarked from the proceeds of the Diamond Jubilee celebration on April 2016, Research and...

Research paper thumbnail of Small - Incision Technique for Med-El Combi 40+™ Implantation

Philippine Journal of Otolaryngology-Head and Neck Surgery

Objectives: 1) To present a technique for implanting the Med-El Combi 40+™ using a small incision... more Objectives: 1) To present a technique for implanting the Med-El Combi 40+™ using a small incision with minimal access. 2) To describe the short term postsurgical outcomes in these patients. Methods: Two patients (1 child and 1 adult) underwent a novel small incision technique for implantation of the Med-El Combi 40+™ cochlear implant device. The short term outcomes in these two patients were described and compared with previous experience using the standard implantation technique citing advantages and possible limitations. As these two patients had bilateral implantation utilizing different techniques on the two sides interesting comparisons could be made on the same individuals. Results: The preliminary experience with a novel small incision technique for the Med-El Combi 40+™ implantation shows encouraging results in terms of healing and initial performance of these patients. Conclusion: This small incision technique may be offered to patients especially to those who wish to...

Research paper thumbnail of Audiological Manifestations in Kabuki (Niikawa-Kuroki) Syndrome

Philippine Journal of Otolaryngology-Head and Neck Surgery

Objective: To describe the audiological profile, clinical features and briefly summarize the spee... more Objective: To describe the audiological profile, clinical features and briefly summarize the speech and language development of a child with Kabuki syndrome (KS). KS is a rare malformation syndrome that usually presents with mental retardation and multiple congenital anomalies including ear diseases and hearing loss. Methods: Design: Case report Setting: Tertiary Public University Hospital Subject: One patient Results: A five-year-old female diagnosed with KS at age three presented with moderate to severe conductive hearing loss in the right ear with a drop at the high frequencies and moderate to severe conductive sloping hearing loss in the left ear. She also had fluctuating tympanometric findings. She was fit with binaural hearing aids. Conclusion: Ear diseases and hearing loss should immediately be considered in patients diagnosed with KS. A comprehensive audiological and otolaryngological evaluation should also be performed when presented with a KS case. Keywords: Kabuki...

Research paper thumbnail of Tierry F. Garcia, MD (1919-2016) “The Most Good for the Most People”

Philippine Journal of Otolaryngology-Head and Neck Surgery

Dr. Tierry Garcia was born December 20, 1919 as one of nine children of Dr. Silverio F. Garcia fr... more Dr. Tierry Garcia was born December 20, 1919 as one of nine children of Dr. Silverio F. Garcia from Bocaue, Bulacan (UPCM 1912) and Elisea Trijo Ballesteros (UP Pharmacy) from Sorsogon. He was married to Amanda, wife of 63 years, and the couple was blessed with three children: Tierry, Jr., Sofia Garcia – Buder, M.D. (a third generation UPCM graduate), and Angela. According to Sofia he “led a life of service to God and to his fellowman, both professionally and personally. His greatest professional legacies for posterity include being among the founding fathers and past Chairman of the Department of Ear, Nose and Throat at the UP-PGH; the Philippine Society of Otorhinolaryngology; and the Manila Doctors' Hospital. He was the last of the small group of pioneers over six decades ago who helped pave the way for the delivery of modern day ENT care to the Filipino people whom he loved.” She continues: “like his father before him, a former surgeon and governor of Sorsogon,” he “str...

Research paper thumbnail of Congenital Oval Window Aplasia: An Unusual Cause of Conductive Hearing Loss in an Adult

Philippine Journal of Otolaryngology-Head and Neck Surgery

Objective: To report a case of congenital oval window aplasia (COWA) in a Filipino adult presenti... more Objective: To report a case of congenital oval window aplasia (COWA) in a Filipino adult presenting with unilateral maximal conductive hearing loss and discuss the diagnostic considerations, pathophysiology and management. Methods: Study Design: Case report Subjects: One (1) Setting: Tertiary Public Referral Center Results: Audiometric evaluation showed a maximal unilateral left conductive hearing loss. High resolution temporal bone CT showed absence of the oval window on the left along with facial and stapes abnormalities. Exploratory tympanotomy showed an aberrant facial nerve, monopodal and abnormally located stapes and absent oval window. Postoperative hearing gain achieved after a neo-oval window and Schuknecht piston wire prosthesis remained stable over two years. Conclusion: A congenital minor ear anomaly classified as Cremers Class 4a in which a congenital oval window aplasia was associated with an aberrant facial nerve anomaly and a ...

Research paper thumbnail of Exome sequencing reveals novel variants and unique allelic spectrum for hearing impairment in Filipino cochlear implantees

Clinical Genetics

To the Editor: Genetic hearing impairment is mostly non-syndromic (80%), and >6000 causal vari... more To the Editor: Genetic hearing impairment is mostly non-syndromic (80%), and >6000 causal variants in >100 genes have been identified. Generally, in hearing-impaired patients of Asian descent, GJB2 variants are most common (36%), followed by variants in SLC26A4 (MIM 605646), MYO15A (MIM 602666) and CDH23 (MIM 605516). Here, we report seven novel variants in Filipino cochlear implantees, suggesting that the allelic spectrum for non-/syndromic hearing impairment in Filipinos is unique. The UP Manila Research Ethics Board approved the study. Adult subjects and parents of pediatric patients provided informed consent. DNA samples and clinical data were obtained from 30 cochlear implantees with bilateral, severe-to-profound, congenital, non-progressive hearing loss as previously described. After excluding one patient with GJB2 c.[35delG];[235delC], 29 DNA samples were submitted for exome sequencing, of which four are homozygous for SLC26A4 c.706C>G (p.(Leu236Val)). For the 25 GJB2-/SLC26A4negative patients, homozygous/heterozygous coding variants within 132 non-/syndromic hearing impairment genes were selected if with minor allele frequency (MAF) < 0.005 in any gnomAD population. Rare variants were selected further if considered damaging by MutationTaster (www.mutationtaster.org) and/or ≥2 dbNSFP (sites.google. com/site/jpopgen/dbNSFP) tools. Eleven Filipino-descent US families with no history of hearing impairment were ascertained for MAF estimation for speech delay (SDFIL) and were Sanger-sequenced for selected exome variants. Variants with zero MAF in the SDFIL cohort were then screened using samples from ≥88 unrelated Filipinos from the Cebu Longitudinal Health and Nutrition Survey, a cohort examined for various health outcomes. Screened exome variants were excluded due to increased MAF, lack of a second rare variant in an autosomal recessive gene and/or poor clinical correlation. Of 30 Filipino cochlear implantees, we identified a genetic cause in half. Seven novel hearing loss variants were discovered (Table 1): CHD7 (MIM 608892) c.7312C>G (p.(Gln2438Glu)); COL4A3 (MIM 120070) c.764C>T (p.(Thr255Met)); DFNA5 (MIM 600994) c.1277_1279delATG (p.(Asp426del)); EYA4 (MIM 603550) c.1109G>A (p.(Arg370His)); MYH14 (MIM 608568) c.2971G>A (p.(Glu991Lys)); MYO15A c.263C>T (p.(Thr88Met)); and OTOA (MIM 607038) c.2301 +1G>T. Patient #28 with the CHD7 variant has microcephaly and seizures, both known features of CHARGE syndrome (MIM 214800). Additionally, he has left superior semicircular canal dehiscence (SSCD) but no vertigo or dizziness. Both DFNA5 c.1277_1279delATG and EYA4 c.1109G>A were previously identified through systematic clinical genetic screening and are annotated in ClinVar (www.ncbi.nlm.nih. gov/clinvar/) as variants of unknown significance. Patient #4 with the EYA4 variant complains of dizziness and balance problems; temporal bone findings include right enlarged vestibular aqueduct and a left jugular bulb diverticulum that impinges onto the ipsilateral vestibular aqueduct. COL4A3 c.764C>T was previously reported for familial kidney disease but not hearing impairment. MYH14 c.2971G>A is cited in the Leiden Open Variation Database (www.lovd.nl/3.0/) as likely benign but was not clarified for non-syndromic DFNA4A (MIM 600652) or peripheral neuropathy, myopathy, hoarseness and hearing loss (PNMHH; MIM 614369). ThisMYH14 variant is the only rare, damaging variant identified in patient #26, who has developmental delay and left foot inversion. Variants CDH23 c.68-3C>T and c.4762C>T (p.(Arg1588Trp)), KCNQ4 (MIM 603537) c.546C>G (p.(Phe182Leu)), and WFS1 (MIM 606201) c.708C>G (p.(Ser236Arg)) have been previously reported for hearing impairment. Patient #10 with the KCNQ4 variant has SSCD on the left but no vestibular symptoms. WFS1 c.708C>G was reported in a patient with compound heterozygous WFS1 variants and autosomal recessive Wolfram syndrome (MIM 222300). Patient #16 has no second WFS1 coding variant but has birth history of cord coil, white matter disease and mild motor delay. Clinical data helped identify the correct gene when multiple potentially causal variants were present. Patients with pathogenic variants had higher pre-surgical audiometric thresholds at ≥1 kHz (Wilcoxon P < 0.05). However, there was no significant difference in post-surgical thresholds, suggesting that carriage of the genetic variants reported here does not determine the outcome of cochlear implantation, with average implant-aided hearing at 38 dB across frequencies. Therefore for carriers of these variants, cochlear implantation remains an excellent option for rehabilitation. Received: 11 December 2018 Revised: 18 January 2019 Accepted: 23 January 2019 DOI: 10.1111/cge.13515

Research paper thumbnail of Genetic counseling in an indigenous Filipino community with a high prevalence of A2ML1-related otitis media

Journal of community genetics, Jan 15, 2018

In this report, we describe the knowledge and beliefs on causes and management of otitis media of... more In this report, we describe the knowledge and beliefs on causes and management of otitis media of an indigenous Filipino community with a high prevalence of otitis media that is associated with an A2ML1 variant. Community lectures and individual genetic counseling were provided as intervention. Knowledge, beliefs, and health care-seeking behavior pertaining to otitis media were assessed pre- and post-genetic counseling. Twenty-five heads of households were interviewed. Beliefs regarding etiology of ear discharge varied widely, with swimming in the sea as the most commonly cited cause of ear discharge. During the post-counseling session, poor personal hygiene, dirty environment, and familial inheritance were mentioned as risk factors for otitis media or ear discharge. Knowledge about the genotypes for the A2ML1 variant and otitis media diagnoses within the household influenced beliefs on the role of hygiene and genetic susceptibility to otitis media and attitudes towards health care-...

Research paper thumbnail of FUT2 Variants Confer Susceptibility to Familial Otitis Media

The American Journal of Human Genetics

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154*) is assoc... more Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154*) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202*) variant co-segregates with otitis media in a Filipino pedigree (LOD ¼ 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p ¼ 1.2 3 10 À5) and US trios (TDT p ¼ 0.01). The c.461G>A (p.Trp154*) variant was also overtransmitted in US trios (TDT p ¼ 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10 À7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p ¼ 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154*, and p.Arg202*-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.

Research paper thumbnail of THE ELECTRICALLY ELICITED STAPEDIUS REFLEX THRESHOLD AS AN ESTIMATE OF MAXIMUM COMFORT LEVEL IN MedEl COMBI 40 and COMBI 40+ IMPLANTs IN THE PHILIPPINES

THE ELECTRICALLY ELICITED STAPEDIUS REFLEX THRESHOLD AS AN ESTIMATE OF MAXIMUM COMFORT LEVEL IN MedEl COMBI 40 and COMBI 40+ IMPLANTs IN THE PHILIPPINES, 2000

The electrically stimulated middle ear muscle reflex (eSRT) threshold was examined as an estimate... more The electrically stimulated middle ear muscle reflex (eSRT) threshold was examined as an estimate of maximum comfort levels (MCLs) in Med-El Combi 40 and Combi 40+ implant clients in the Philippines. These objective MCLs were compared with the previous behaviourally obtained (subjective) MCLs. There was a moderate positive correlation between the subjective and objective maps. The correlation tended to be stronger for older children and those who had been seen for a greater number of mapping sessions. There was a clear trend showing that as the number of mapping sessions increased, the subjective MCL’s approached the eSRT. For this reason, the eSRT thresholds are considered to be a good first estimate of the true MCLs especially in young children who may have no clear concept of „loudness“ due to both age and lack of experience with auditory input. The eSRT remained stable (low variance) from trial to trial. For practical reasons, it is also recommended that the subjective/observational technique for mapping not be abandoned since some children may not demonstrate a clear eSRT for a variety of reasons. This paper also includes a discussion of various issues that arose during the study which provide both food for thought and a potential basis for further research.

Key words: MCL Maximum Comfort Levels, Stapedius Reflex, Cochlear Implants, Mapping, Dynamic Range, Pediatric Audiology

Research paper thumbnail of Auditory Brainstem Implantation Improves Speech Recognition in Neurofibromatosis Type II Patients

Acoustic neuroma · Auditory brainstem implant · Nonauditory side effects · Open-set sentence reco... more Acoustic neuroma · Auditory brainstem implant · Nonauditory side effects · Open-set sentence recognition · Subjective benefits · Vestibular schwannoma This prospective study aimed to determine speech understanding in neurofibromatosis type II (NF2) patients following implantation of a MED-EL COMBI 40+ auditory brainstem implant (ABI). Patients (n = 32) were enrolled postsurgically. Nonauditory side effects were evaluated at fitting and audiological performance was determined using the Sound Effects Recognition Test (SERT), Monosyllable-Trochee-Polysyllable (MTP) test and open-set sentence tests. Sub-jective benefits were determined by questionnaire. ABI activation was documented in 27 pa-tients, 2 patients were too ill for testing and 3 patients were without any auditory perception. SERT and MTP outcomes under auditory-only conditions improved significantly between first fitting and 12-month follow-up. Open-set sentence recognition improved from 5 % at first fit-ting to 37 % after 1...

Research paper thumbnail of Agreement between Human Voice (“Baah”) Test and Otoacoustic Emissions in Screening of Infants for Binaural Hearing Loss

Research paper thumbnail of Agreement between Human Voice (“Baah”) Test and Otoacoustic Emissions in Screening of Infants for Binaural Hearing Loss

Presented at the 16th ASEAN ORL-HNS Congress, November 11, 2015, The Empress Convention Center, C... more Presented at the 16th ASEAN ORL-HNS Congress, November 11, 2015, The Empress Convention Center, Chiang Mai, Thailand, through an educational grant of ADP Pharma Corporation, and as a poster presentation at the 18th Anniversary of the National Institutes of Health, 14th UP Manila Science and Technology Week, and at the 7th Anniversary of the Metro Manila Research and Development Consortium, February 17-18, 2016, SMX Convention Center, Mall of Asia.

Research paper thumbnail of The Cost-Effectiveness and Budget Impact of a Community-based Universal Newborn Hearing Screening Program in the Philippines

Research paper thumbnail of The SLC26A4 c.706C>G (p.Leu236Val) Variant is a Frequent Cause of Hearing Impairment in Filipino Cochlear Implantees

Otology & Neurotology

HYPOTHESIS Variants in SLC26A4 are an important cause of congenital hearing impairment in the Phi... more HYPOTHESIS Variants in SLC26A4 are an important cause of congenital hearing impairment in the Philippines. BACKGROUND Cochlear implantation is a standard rehabilitation option for congenital hearing impairment worldwide, but places a huge cost burden in lower-income countries. The study of risk factors such as genetic variants that may help determine genetic etiology of hearing loss and also predict cochlear implant outcomes is therefore beneficial. METHODS DNA samples from 29 GJB2-negative Filipino cochlear implantees were Sanger-sequenced for the coding exons of SLC26A4. Exome sequencing was performed to confirm results. RESULTS Four cochlear implantees with bilaterally enlarged vestibular aqueducts (EVA) were homozygous for the pathogenic SLC26A4 c.706C>G (p.Leu236Val) variant, which has a minor allele frequency of 0.0015 in Filipino controls. In patients with the SLC26A4 variant there was no association between cochlear implant outcome and age at implantation or duration of implant. There was also no association between the occurrence of the SLC26A4 variant and postsurgical audiometric thresholds and parents' evaluation of aural/oral performance of children (PEACH) scores. On the other hand, the SLC26A4 variant increased presurgical median audiometric thresholds (p = 0.01), particularly at 500 to 2000 Hz. CONCLUSION The SLC26A4 c.706C>G (p.Leu236Val) variant is a frequent cause of congenital hearing impairment in Filipinos and is associated with bilateral EVA and increased presurgical audiometric thresholds, but does not adversely affect post-implant outcomes.

Research paper thumbnail of Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants

Journal of Medical Genetics

BackgroundOtitis media (OM) susceptibility has significant heritability; however, the role of rar... more BackgroundOtitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.MethodsWe performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues.ResultsA large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the oute...

Research paper thumbnail of In Reply to the Letter to the Editor regarding “Temporal Bone Chondroblastoma: Systematic Review of Clinical Features and Outcomes”

Research paper thumbnail of Cost-Analysis of Universal Newborn Hearing Screening in the Philippines

Research paper thumbnail of Auditory Brainstem Response Latencies of Infants and Maternal Exposure to Environmental Toxic Products

Research paper thumbnail of Baseline Knowledge, Attitudes, and Practices of Healthcare Practitioners in Rizal Province, Philippines toward Implementing the Universal Newborn Hearing Screening Program

Acta Medica Philippina

Objective. The study describes the current knowledge, attitudes, and practices of healthcare prac... more Objective. The study describes the current knowledge, attitudes, and practices of healthcare practitioners in Rizal province regarding the implementation of the universal newborn hearing screening program (UNHSP).Materials and Methods. A descriptive phenomenologic research design through focus group discussions with pediatric and OBGYN consultants in a government hospital, nurses from private primary and secondary hospitals, midwives from private birthing homes, and rural health workers.Results. Attitudes. All participants recognized that they had important roles in implementing the program except the OBGYN consultants as they felt that information about the UNHSP should be provided by pediatricians. Practices. The lack of a screening device, trained personnel, and a referral network were the most common barriers in implementing the program. Knowledge. Most participants lacked specific knowledge about hearing loss and its implications in the UNHSP.Conclusion. Most participants were ...

Research paper thumbnail of A Chronicle of Change: the Core Values We Cherish

Philippine Journal of Otolaryngology Head and Neck Surgery

As we approach the last quarter of the year, it is time that Fellows of the Philippine Society of... more As we approach the last quarter of the year, it is time that Fellows of the Philippine Society of Otolaryngology-Head and Neck Surgery (PSOHNS) receive this report from the President and the Board of Trustees. Following the successful staging of the midyear congress at EDSA Shangrila and distribution of the coffeetable book-- another chronicle of our rich history-- we also witnessed the launching of the advocacy campaign “Change is in the Air” led by Philippine Academy of Rhinology (PAR) Chair Dr. Tony Chua with Drs. Mari Enecilla and Joel Romuladez that even saw print in the newspapers. Despite the challenges, the support we received from our pharmaceutical friends was tremendous and the avowed fund support for advocacy from the proceeds of that congress amounting to a little over P2 million will certainly go a long way for our future campaigns. Our new home and headquarters at 27 Manga Road, Quezon City was finally inaugurated last July 8. Legal ownership with the title of the pro...

Research paper thumbnail of President’s inaugural address Philippine Society of Otolargyngology head and neck Surgery annual Congress December 2, 2015

Philippine Journal of Otolaryngology Head and Neck Surgery

Past Presidents of the PSO-HNS especially founding President Dr. Tierry Garcia, President of the ... more Past Presidents of the PSO-HNS especially founding President Dr. Tierry Garcia, President of the PBO-HNS Dr. Rudy Nonato, Presidents of the chapters and Chairs of the subspecialty groups, co-Fellows of the society, friends, guests, ladies and gentlemen. At the threshold of the 60th anniversary of this venerable society, I stand here today as the humble recipient of your trust and confidence as your President. As a child I have seen the photos of the heroic founders and had been witness to the lasting friendship between them. I was in high school when my father, Dr. Armando T. Chiong, Sr. became the 10th President of the organization. I now follow my brother, President Dr. Armando Chiong, Jr. to continue the programs he started. Such laudable programs started by the past years’ BOT with the advocacy map, public awareness, chapter and institutional initiatives will be continued. With the funding earmarked from the proceeds of the Diamond Jubilee celebration on April 2016, Research and...

Research paper thumbnail of Small - Incision Technique for Med-El Combi 40+™ Implantation

Philippine Journal of Otolaryngology-Head and Neck Surgery

Objectives: 1) To present a technique for implanting the Med-El Combi 40+™ using a small incision... more Objectives: 1) To present a technique for implanting the Med-El Combi 40+™ using a small incision with minimal access. 2) To describe the short term postsurgical outcomes in these patients. Methods: Two patients (1 child and 1 adult) underwent a novel small incision technique for implantation of the Med-El Combi 40+™ cochlear implant device. The short term outcomes in these two patients were described and compared with previous experience using the standard implantation technique citing advantages and possible limitations. As these two patients had bilateral implantation utilizing different techniques on the two sides interesting comparisons could be made on the same individuals. Results: The preliminary experience with a novel small incision technique for the Med-El Combi 40+™ implantation shows encouraging results in terms of healing and initial performance of these patients. Conclusion: This small incision technique may be offered to patients especially to those who wish to...

Research paper thumbnail of Audiological Manifestations in Kabuki (Niikawa-Kuroki) Syndrome

Philippine Journal of Otolaryngology-Head and Neck Surgery

Objective: To describe the audiological profile, clinical features and briefly summarize the spee... more Objective: To describe the audiological profile, clinical features and briefly summarize the speech and language development of a child with Kabuki syndrome (KS). KS is a rare malformation syndrome that usually presents with mental retardation and multiple congenital anomalies including ear diseases and hearing loss. Methods: Design: Case report Setting: Tertiary Public University Hospital Subject: One patient Results: A five-year-old female diagnosed with KS at age three presented with moderate to severe conductive hearing loss in the right ear with a drop at the high frequencies and moderate to severe conductive sloping hearing loss in the left ear. She also had fluctuating tympanometric findings. She was fit with binaural hearing aids. Conclusion: Ear diseases and hearing loss should immediately be considered in patients diagnosed with KS. A comprehensive audiological and otolaryngological evaluation should also be performed when presented with a KS case. Keywords: Kabuki...

Research paper thumbnail of Tierry F. Garcia, MD (1919-2016) “The Most Good for the Most People”

Philippine Journal of Otolaryngology-Head and Neck Surgery

Dr. Tierry Garcia was born December 20, 1919 as one of nine children of Dr. Silverio F. Garcia fr... more Dr. Tierry Garcia was born December 20, 1919 as one of nine children of Dr. Silverio F. Garcia from Bocaue, Bulacan (UPCM 1912) and Elisea Trijo Ballesteros (UP Pharmacy) from Sorsogon. He was married to Amanda, wife of 63 years, and the couple was blessed with three children: Tierry, Jr., Sofia Garcia – Buder, M.D. (a third generation UPCM graduate), and Angela. According to Sofia he “led a life of service to God and to his fellowman, both professionally and personally. His greatest professional legacies for posterity include being among the founding fathers and past Chairman of the Department of Ear, Nose and Throat at the UP-PGH; the Philippine Society of Otorhinolaryngology; and the Manila Doctors' Hospital. He was the last of the small group of pioneers over six decades ago who helped pave the way for the delivery of modern day ENT care to the Filipino people whom he loved.” She continues: “like his father before him, a former surgeon and governor of Sorsogon,” he “str...

Research paper thumbnail of Congenital Oval Window Aplasia: An Unusual Cause of Conductive Hearing Loss in an Adult

Philippine Journal of Otolaryngology-Head and Neck Surgery

Objective: To report a case of congenital oval window aplasia (COWA) in a Filipino adult presenti... more Objective: To report a case of congenital oval window aplasia (COWA) in a Filipino adult presenting with unilateral maximal conductive hearing loss and discuss the diagnostic considerations, pathophysiology and management. Methods: Study Design: Case report Subjects: One (1) Setting: Tertiary Public Referral Center Results: Audiometric evaluation showed a maximal unilateral left conductive hearing loss. High resolution temporal bone CT showed absence of the oval window on the left along with facial and stapes abnormalities. Exploratory tympanotomy showed an aberrant facial nerve, monopodal and abnormally located stapes and absent oval window. Postoperative hearing gain achieved after a neo-oval window and Schuknecht piston wire prosthesis remained stable over two years. Conclusion: A congenital minor ear anomaly classified as Cremers Class 4a in which a congenital oval window aplasia was associated with an aberrant facial nerve anomaly and a ...

Research paper thumbnail of Exome sequencing reveals novel variants and unique allelic spectrum for hearing impairment in Filipino cochlear implantees

Clinical Genetics

To the Editor: Genetic hearing impairment is mostly non-syndromic (80%), and >6000 causal vari... more To the Editor: Genetic hearing impairment is mostly non-syndromic (80%), and >6000 causal variants in >100 genes have been identified. Generally, in hearing-impaired patients of Asian descent, GJB2 variants are most common (36%), followed by variants in SLC26A4 (MIM 605646), MYO15A (MIM 602666) and CDH23 (MIM 605516). Here, we report seven novel variants in Filipino cochlear implantees, suggesting that the allelic spectrum for non-/syndromic hearing impairment in Filipinos is unique. The UP Manila Research Ethics Board approved the study. Adult subjects and parents of pediatric patients provided informed consent. DNA samples and clinical data were obtained from 30 cochlear implantees with bilateral, severe-to-profound, congenital, non-progressive hearing loss as previously described. After excluding one patient with GJB2 c.[35delG];[235delC], 29 DNA samples were submitted for exome sequencing, of which four are homozygous for SLC26A4 c.706C>G (p.(Leu236Val)). For the 25 GJB2-/SLC26A4negative patients, homozygous/heterozygous coding variants within 132 non-/syndromic hearing impairment genes were selected if with minor allele frequency (MAF) < 0.005 in any gnomAD population. Rare variants were selected further if considered damaging by MutationTaster (www.mutationtaster.org) and/or ≥2 dbNSFP (sites.google. com/site/jpopgen/dbNSFP) tools. Eleven Filipino-descent US families with no history of hearing impairment were ascertained for MAF estimation for speech delay (SDFIL) and were Sanger-sequenced for selected exome variants. Variants with zero MAF in the SDFIL cohort were then screened using samples from ≥88 unrelated Filipinos from the Cebu Longitudinal Health and Nutrition Survey, a cohort examined for various health outcomes. Screened exome variants were excluded due to increased MAF, lack of a second rare variant in an autosomal recessive gene and/or poor clinical correlation. Of 30 Filipino cochlear implantees, we identified a genetic cause in half. Seven novel hearing loss variants were discovered (Table 1): CHD7 (MIM 608892) c.7312C>G (p.(Gln2438Glu)); COL4A3 (MIM 120070) c.764C>T (p.(Thr255Met)); DFNA5 (MIM 600994) c.1277_1279delATG (p.(Asp426del)); EYA4 (MIM 603550) c.1109G>A (p.(Arg370His)); MYH14 (MIM 608568) c.2971G>A (p.(Glu991Lys)); MYO15A c.263C>T (p.(Thr88Met)); and OTOA (MIM 607038) c.2301 +1G>T. Patient #28 with the CHD7 variant has microcephaly and seizures, both known features of CHARGE syndrome (MIM 214800). Additionally, he has left superior semicircular canal dehiscence (SSCD) but no vertigo or dizziness. Both DFNA5 c.1277_1279delATG and EYA4 c.1109G>A were previously identified through systematic clinical genetic screening and are annotated in ClinVar (www.ncbi.nlm.nih. gov/clinvar/) as variants of unknown significance. Patient #4 with the EYA4 variant complains of dizziness and balance problems; temporal bone findings include right enlarged vestibular aqueduct and a left jugular bulb diverticulum that impinges onto the ipsilateral vestibular aqueduct. COL4A3 c.764C>T was previously reported for familial kidney disease but not hearing impairment. MYH14 c.2971G>A is cited in the Leiden Open Variation Database (www.lovd.nl/3.0/) as likely benign but was not clarified for non-syndromic DFNA4A (MIM 600652) or peripheral neuropathy, myopathy, hoarseness and hearing loss (PNMHH; MIM 614369). ThisMYH14 variant is the only rare, damaging variant identified in patient #26, who has developmental delay and left foot inversion. Variants CDH23 c.68-3C>T and c.4762C>T (p.(Arg1588Trp)), KCNQ4 (MIM 603537) c.546C>G (p.(Phe182Leu)), and WFS1 (MIM 606201) c.708C>G (p.(Ser236Arg)) have been previously reported for hearing impairment. Patient #10 with the KCNQ4 variant has SSCD on the left but no vestibular symptoms. WFS1 c.708C>G was reported in a patient with compound heterozygous WFS1 variants and autosomal recessive Wolfram syndrome (MIM 222300). Patient #16 has no second WFS1 coding variant but has birth history of cord coil, white matter disease and mild motor delay. Clinical data helped identify the correct gene when multiple potentially causal variants were present. Patients with pathogenic variants had higher pre-surgical audiometric thresholds at ≥1 kHz (Wilcoxon P < 0.05). However, there was no significant difference in post-surgical thresholds, suggesting that carriage of the genetic variants reported here does not determine the outcome of cochlear implantation, with average implant-aided hearing at 38 dB across frequencies. Therefore for carriers of these variants, cochlear implantation remains an excellent option for rehabilitation. Received: 11 December 2018 Revised: 18 January 2019 Accepted: 23 January 2019 DOI: 10.1111/cge.13515

Research paper thumbnail of Genetic counseling in an indigenous Filipino community with a high prevalence of A2ML1-related otitis media

Journal of community genetics, Jan 15, 2018

In this report, we describe the knowledge and beliefs on causes and management of otitis media of... more In this report, we describe the knowledge and beliefs on causes and management of otitis media of an indigenous Filipino community with a high prevalence of otitis media that is associated with an A2ML1 variant. Community lectures and individual genetic counseling were provided as intervention. Knowledge, beliefs, and health care-seeking behavior pertaining to otitis media were assessed pre- and post-genetic counseling. Twenty-five heads of households were interviewed. Beliefs regarding etiology of ear discharge varied widely, with swimming in the sea as the most commonly cited cause of ear discharge. During the post-counseling session, poor personal hygiene, dirty environment, and familial inheritance were mentioned as risk factors for otitis media or ear discharge. Knowledge about the genotypes for the A2ML1 variant and otitis media diagnoses within the household influenced beliefs on the role of hygiene and genetic susceptibility to otitis media and attitudes towards health care-...

Research paper thumbnail of FUT2 Variants Confer Susceptibility to Familial Otitis Media

The American Journal of Human Genetics

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154*) is assoc... more Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154*) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202*) variant co-segregates with otitis media in a Filipino pedigree (LOD ¼ 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p ¼ 1.2 3 10 À5) and US trios (TDT p ¼ 0.01). The c.461G>A (p.Trp154*) variant was also overtransmitted in US trios (TDT p ¼ 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10 À7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p ¼ 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154*, and p.Arg202*-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.

Research paper thumbnail of Hearing Preservation in Acoustic Neuroma Surgery: Value of Monitoring Cochlear Nerve Action Potentials

Otolaryngology-Head and Neck Surgery