Triploidy that escaped diagnosis using chromosomal microarray testing in early pregnancy loss: Two cases and a literature review

About 15% to 20% of all clinically recognized pregnancies result in spontaneous abortion or miscarriage, and chromosomal anomalies can be identified in up to 50% of first trimester miscarriages. Chromosomal microarray analysis (CMA) is currently considered first-tier testing for detecting fetal chromosomal abnormalities and is supported by the absence of cell culture failure or erroneous results due to cell contamination in pregnancy loss. Triploidy is a lethal chromosome number abnormality characterized by an extra haploid set of chromosomes. Triploidy is one of the most common chromosomal aberrations in first trimester spontaneous abortions. Here, we report two cases of triploidy abortion that were not detected using array comparative genomic hybridization-based CMA. The aim of this report was to remind clinicians of the limitations of chromosomal testing and the misdiagnosis that can result from biased test selection.

Clinicopathological features of premature ovarian insufficiency associated with chromosome abnormalities

PURPOSE: The aim of this study was to investigate the clinicopathological features of premature ovarian insufficiency (POI) associated with chromosomal abnormalities. MATERIALS AND METHODS: This was a retrospective study of POI patients with chromosomal abnormalities diagnosed between January 2009 and December 2017. The definition of POI is based on hypergonadotropinism of 40 or greater in follicle stimulating hormone (FSH) measurements at age 40 years or less. FSH was measured twice at least 4 weeks apart. Karyotyping using peripheral blood for chromosomal testing was conducted in all patients diagnosed with POI. We analyzed the clinical characteristics and genetic causes of patients who were diagnosed with POI. RESULTS: Forty patients were diagnosed with POI including 9 (22.5%) with identified chromosomal abnormalities. The mean age at diagnosis was 23.1±7.8 years (ranging between 14 and 39). Three patients did not experience menarche. The presenting complaints were short stature in one case, one case of amenorrhea with ambiguous external genitals, one case of infertility, and six related to menstruation such as oligomenorrhea or irregular rhythm. Turner syndrome was diagnosed in four cases, Xq deletion in one case, trisomy X in two cases, and 46,XY disorder of sexual development in two other patients. CONCLUSION: Patients diagnosed with POI carrying the same type of chromosomal abnormality manifest different phenotypes. The management protocol also needs to be changed depending on the diagnosis. A karyotype is indicated for accurate diagnosis and proper management of POI in patients, with or without stigmata of chromosomal abnormalities.

Split hand/foot malformation with long-bone deficiency and BHLHA9 duplication: A prenatal diagnosis report

Distal limb deformities are congenital malformations with phenotypic variability and high genetic heterogeneity. Split hand/foot malformation, also known as ectrodactyly, is a congenital limb malformation characterized by a defect of the central rays of the hands and/or feet. Split hand/foot malformation with long-bone deficiency (SHFLD) is a rare condition related to a 17p13.3 duplication. Recently, genomic duplications encompassing BHLHA9 have been associated with SHFLD. We report a case of SHFLD presenting with campomelia of the right femur, bilateral agenesis of fibulae, bilateral club feet, and oligosyndactyly of the hands and feet, that was associated with a 17p13.3 duplication, as determined prenatally using array comparative genomic hybridization.

Analysis of increased nuchal translucency: Chorionic villi sampling and second-trimester level II sonography

PURPOSE: To assess the outcomes of increased fetal nuchal translucency (NT), to aid in prenatal counseling and management in our practice. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent first trimester fetal karyotyping using chorionic villi sampling (CVS) and second trimester level II sonography for a fetal NT thickness > or =3.0 mm between 11 weeks and 13 weeks 6 days' gestation, at Gyeongsang National University Hospital. Pediatric medical records and a telephone interview were used to follow-up live-born children. Exclusion criteria included incomplete data and CVS for other indications. RESULTS: Seventy cases met the inclusion criteria (median NT thickness, 4.7 mm; range, 3.0-16.1 mm). Twenty-nine cases (41.4%) were aneuploid. The prevalence of chromosomal defects increased with NT thickness: NT 3.0-3.4 mm, 16.7%; NT 3.5-4.4 mm, 27.3%; NT 4.5-5.4 mm, 66.7%; NT 5.5-6.4 mm, 37.5%; NT > or =6.5 mm, 62.5%. The most common karyotype abnormality was trisomy 18 (n=12), followed by trisomy 21 (n=9). In chromosomally normal fetuses (n=41), fetal death occurred in 2 cases (4.9%), and structural malformations were found in 11 cases (26.8%). In chromosomally and anatomically normal fetuses (n=28), one child had neurodevelopmental delay (3.6%). Twenty-eight infants who had a prenatal increased NT were alive and well at follow-up (40%). CONCLUSION: Outcomes of increased fetal NT might help inform prenatal counseling and management. The high prevalence of chromosomal defects associated with increased fetal NT implies that CVS should be performed in the first trimester, particularly considering the stress associated with an uncertain diagnosis.

A Case of Nasopharyngeal Carcinoma Presenting as Middle Ear Tumor / 대한이비인후과학회지

Nasopharyngeal carcinoma (NPC) evolves most commonly from the pharyngeal recess posteromedial to the medial crura of the Eustachian tube opening in the nasopharynx. Therefore unilateral middle ear effusion with hearing loss is a common presenting symptom of NPC, and its presence in adult patients make physicians suspect NPC. Recently, we experienced a 72- year-old female patient with advanced NPC which invaded Eustachian tube and middle ear cavity. She had long standing chronic otitis media with large perforation of tympanic membrane. Because of tympanic membrane perforation, she did not have any Eustachian tube-related symptoms such as newly developing ear fullness or hearing loss and even the physician had overlooked the diagnosis of NPC. Her NPC was diagnosed at a very advanced stage after performing biopsy of middle ear tumor. This case report shows that NPC can present with very unusual findings like middle ear tumor.

A Case of Temporomandibular Joint Disorder Accompanied with Ear Bleeding / 대한이비인후과학회지

Temporomandibular joint disorder (TMD) is a generic term used for any problem concerning the jaw joint. The clinical signs of TMD are crepitus associated with movement, restriction of jaw movements, and pain within the joint cavity. But ear bleeding and an external auditory canal (EAC) mass as presenting symptoms are rare. We report the case of 78-year-old man with TMD, whose initial symptoms were ear bleeding, and temporomandibular pain intensifying when he is chewing, accompanied by an EAC mass. Physical examination revealed a reddish mass that originated from the anterior wall of EAC and bled when touched. Computed tomography showed a mass with soft tissue density and a bony defect in the anterior EAC wall. After conducting arthrocentesis and lavage repetitively, the wound was healed completely. It is likely that the patient's ear bleeding was due to patent foramen of Huschke or erosion of the anterior wall of EAC due to temporomandibular joint inflammation.

Expression Profile of Fas-Fas Ligand in Spiral Ganglion Cells During Apoptosis

OBJECTIVES: To examine the expression profile of Fas-Fas ligand (FasL) during glutamate (Glu)-induced spiral ganglion cell (SGC) apoptosis. METHODS: Cultured SGCs were treated with 10-mM, 25-mM, and 50-mM concentrations of Glu and incubated for 24 or 48 hours. The expression intensity of FasL, Fas, caspase 3, and morphology of single SGC were evaluated using immunofluorescence staining. RESULTS: In semiquantitative analysis of the Glu-treated SGC, FasL, and caspase 3 expression intensity were increased with concentration- and time-dependent manner. Fas expression intensity did not change with different concentration at 48 hours. In morphologic analysis of the Glu-treated SGC, number of apoptotic cells were increased with concentration- and time-dependent manner. CONCLUSION: FasL was expressed in apoptotic SGCs, suggesting that the Fas-FasL signaling pathway may be involved in the Glu-induced apoptosis of dissociated SGCs.

Clinical Value of Persistent but Downgraded Vesicoureteral Reflux after Dextranomer/Hyaluronic Acid Injection in Children

We aimed to investigate the clinical value of persistent but downgraded vesicoureteral reflux (VUR) after dextranomer/hyaluronic acid (Dx/HA) injection in children. The medical records of 128 children (195 ureters) who underwent Dx/HA injections for VUR were reviewed. The incidences of pre- and post-operative febrile urinary tract infections (UTIs) were analyzed in children with or without persistent VUR on voiding cystourethrography (VCUG) 3 months postoperatively. The surgical results of VUR persistent children who underwent a single additional injection were assessed. The VUR resolved completely in 100 ureters (51.3%), was persistent in 95 ureters, and newly developed in 2 ureters. The incidence of pre/post-operative febrile UTIs were 0.35 +/- 0.39 per year and 0.07 +/- 0.32 per year in VUR resolved children (P < 0.001), and 0.76 +/- 1.18 per year and 0.20 +/- 0.61 per year in VUR persistent children (P < 0.001). A single additional Dx/HA injection (44 ureters) resolved VUR in 29 ureters (65.9%), and also reduced the VUR to grade I in 7 ureters (15.9%), II in 4 (9.1%), and III in 4 (9.1%). Even in children with persistent VUR after Dx/HA injection, the incidence of febrile UTIs decreased markedly. The VUR grade significantly decreases after single additional Dx/HA injection.

A Case of Image-Guided Posterior Tympanotomy in Chronic Otitis Media / 대한이비인후과학회지

Posterior tympanotomy is a procedure performed to access the posterior mesotympanum through a mastoid exposure while preserving the posterior external auditory canal wall. It is dangereous to drill the the site of procedure, as it is surrounded by incuidal fossa superiorly, facial nerve posteriomedially, and chorda tympani nerve anterolaterally, and forms a very narrow pathway. There is always a risk of surgical trauma involving important surgical structures, especially facial nerve and chorda tympani nerve. The development of image-guided surgery (IGS) has significantly improved the performance of many surgical procedures by aiding the identification of surgical landmarks, improving surgical outcomes, rendering the procedure safer and more efficient, especially for beginner otologic surgery, in revision operations, in cases of massive bleeding and tumor of complex anatomy. To see how IGS could help otologic surgeons to identify fine, important structures during posterior tympanotomy, we report a case of posterior tympanotomy in chronic otitis media, which was done using the image-guided surgical technique.

A Case of Image-Guided Surgery in Congenital Aural Atresia / 대한이비인후과학회지

The repair of congenital aural atresia remains one of the most challenging otologic procedures because of the scarcity of surgical landmarks, the complexity and the variety of the temporal bone anatomy, and the limited space for reconstruction. The risks of facial nerve injury and profound sensorineural hearing loss following atresia surgery are common concerns. Furthermore, the rarity of the disease makes it difficult to improve surgical learning. Image-guided surgery may aid otologic surgeons in repairing atresia as it allows identifying the exact position of surgical instruments in relation to the specific anatomy. To our knowledge, there have been no published reports on image-guided atresia surgery in Korea. Herein, we report a case of congenital aural atresia, which was repaired using image-guided surgical technique.

Changes in the Hearing Thresholds of Infants Who Failed the Newborn Hearing Screening Test and in Infants Treated in the Neonatal Intensive Care Unit

OBJECTIVES: The aim of this study was to investigate changes in the hearing thresholds during the first year of life in infants who failed the newborn hearing screening (NHS) test and of infants treated in the neonatal intensive care unit (NICU). METHODS: From March 2007 to November 2010, 193 healthy infants who failed the NHS test and 51 infants who were treated in the NICU were referred for evaluation of hearing acuity. Their hearing was evaluated using impedance audiometry, auditory brainstem response (ABR), and otoacoustic emission before 6 months of age, and follow-up hearing tests were administered before 12 months of age. Changes in their hearing thresholds were then analyzed. RESULTS: Of the 193 healthy infants who failed the NHS test, 60 infants (31%) had normal hearing acuity, 126 infants (65%) had sensorineural hearing loss (SNHL, ABR threshold > or =40 dB) and 7 infants (4%) had auditory neuropathy (AN). On the follow-up hearing tests, which were conducted in 65 infants, 6 infants showed a hearing threshold deterioration of more than 20 dB, and 19 infants showed a hearing threshold improvement of more than 20 dB. Of the 51 infants who were treated in the NICU, 38 infants (75%) had normal hearing acuity, 12 infants (24%) had SNHL, and one infant (2%) had AN. In the follow-up hearing tests, which were performed in 13 infants, one infant with normal hearing progressed to severe hearing loss. Five infants who had SNHL showed a hearing threshold improvement of more than 20 dB, and 4 infants recovered to normal hearing. CONCLUSION: The hearing thresholds of infants with congenital SNHL can change during the first year of life; therefore, the importance of administration of follow-up hearing tests is emphasized. Irreversible intervention such as cochlear implantation should be considered with great caution within the first year after birth.

Rat Mastoid Bullae Obliteration with Hydroxyapatite: Histopathologic Results with Various Size of Hydroxyapatite / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mastoid obliteration is the technique developed to reduce cavity problems after canal wall down mastoidectomy. Different materials have been explored for the technique, and of the variety of materials that have been used for mastoid obliteration, hydroxyapatite has gained particular attention. Hydroxyapatite can be made into a specific particle size, which affects the postoperative result. The aim of this study is to evaluate the histopathologic findings of mastoids obliterated with various particle sizes of hydroxyapatite in the temporal bullae of rat. Materials and Method: Rat bullaes were obliterated with hydroxyapatite and diversified into different particle sizes. In group 1, the mastoids were obliterated with Mimix(R) powder and in groups 2, 3, 4 with Bongros(R). The particle sizes were 0.3-0.6 mm, 0.6-1.0 mm and 1.0-3.0 mm each. After 3 months, the mastoids were examined under the microscope. RESULTS: In group 1, a new bone was formed in a consecutive fashion from the mastoid wall toward the center of the mastoid; there was no inflammation, with the new bone formation constituting 15%. In group 2, 3, 4, the proportion of new bone formation was higher than in the group 1, and constituted 40%, 55% and 60%, respectively. Inflammation was more severe when the particle size became larger. CONCLUSION: New bone formation was faster if larger hydroxyapatite particles were used; however, inflammation also increased. The powder form of hydroxyapatite was slow in new bone formation, but there was little inflammation. We therefore think that the hydroxyapatite is a very safe material.