Progressive Conductive Hearing Loss Research Articles

Laser Stapedotomy for Otosclerosis

Otosclerosis can lead to progressive conductive hearing loss, significantly affecting the quality of life. For patients who choose surgery, the tympanic membrane is elevated and middle ear space is explored. If the surgeon confirms that the stapes is fixed in the oval window, either a stapedotomy or stapedectomy can be performed. In the stapedotomy, the surgeon removes the stapes superstructure, creates a fenestration in the footplate, and places a prosthesis from the incus through the fenestration into the vestibule. In this instance, the patient was able to regain nearly all of the hearing that had been lost as a result of stapes fixation.

An uncommon “third window” in retrofenestral otosclerosis

Otosclerosis is an otologic disease characterized by disordered resorption and deposition of the otic capsule bone. It can lead to progressive conductive, mixed or sensorineural Hearing Loss (HL). In rare cases, it manifests itself with a tendency for massive bone resorption with subsequent formation of cavities (“cavitating otosclerosis”). Cavities can sometimes realize communication between the Cerebrospinal Fluid (CSF) at the Internal Auditory Canal (IAC) and the cochlear duct. In these uncommon cases, a “third-window” phenomenon may be established as a concomitant cause of conductive HL. Therefore, the feasibility of stapes surgery should be evaluated, without underestimating the risk of gusher complications. In this report, we discuss the case of a female patient affected by cavitating otosclerosis realizing a connection between IAC and cochlear duct, with mixed hearing loss.

Role of computed tomography in the preoperative diagnosis of otosclerosis

Otosclerosis is an osteodystrophy of the otic capsule and presents with progressive conductive hearing loss. Imaging studies, especially computed tomography (CT) and cone-beam CT, have gained increased relevance in the diagnosis of otosclerosis. This study investigated whether there is acorrelation between the extent of otosclerosis in high-resolution or cone-beam CT and hearing loss in pure-tone audiometry. Based on an existing classification of otosclerotic foci, aclassification was established. Preoperative CT scans of patients undergoing stapedotomy between 2015 and 2019 were evaluated and classified by two independent otorhinolaryngologists. The preoperative pure-tone audiograms were analysed and compared to the results of CT. Atotal of 168CT studies (i.e., 168ears) in 156patients with intraoperatively confirmed otosclerosis were included in our study. Acorrelation between the extent of the otosclerotic focus or the calculated scores and hearing loss in pure-tone audiometry (air conduction, bone conduction and air-bone-gap) could not be proven. Preoperative CT is not obligatory. However, preoperative imaging using CT or cone-beam CT can be helpful to confirm the diagnosis and exclude other middle or inner ear pathologies as well as in planning of the surgical procedure in the overall context of otoscopy and audiometry. Acorrelation with the degree of hearing impairment could not be demonstrated and remains unclear.

Otosclerosis

Otosclerosis is a primary hereditary disorder of the otic capsule, affecting most commonly the area of the oval window. Stapes footplate fixation results in the immobility of the ossicular chain, which leads to progressive conductive hearing loss. Other symptoms include a sensorinerural component of hearing loss, tinnitus, and vestibular symptoms. Clinical otosclerosis occurs more frequently in women, and the first symptoms usually appear after childbirth in the 3rd decade of life. The etiology includes genetic, infectious, inflammatory, autoimmune, and hormonal factors. Audiological diagnostics for otosclerosis involves a battery of tests that complement one another, and the interrelation of their outcomes has a high predictive value. There are a few classifications of the disease, the majority of which are based on radiological criteria. Imaging studies mainly involve temporal bone high-resolution computed tomography, which has a relatively high sensitivity and specificity for detecting otosclerotic foci. Despite the availability of a wide variety of diagnostic techniques, the final diagnosis is still confirmed intraoperatively. Stapedotomy remains a reasonable primary intervention for the majority of patients with otosclerosis.

Bacterial and Fungal Infections Promote the Bone Erosion Progression in Acquired Cholesteatoma Revealed by Metagenomic Next-Generation Sequencing.

An acquired cholesteatoma generally occurs as a consequence of otitis media and eustachian tube dysfunction. Patients with acquired cholesteatoma generally present with chronic otorrhea and progressive conductive hearing loss. There are many microbes reportedly associated with acquired cholesteatoma. However, conventional culture-based techniques show a typically low detection rate for various pathogenetic bacteria and fungi. Metagenomic next-generation sequencing (mNGS), an emerging powerful platform offering higher sensitivity and higher throughput for evaluating many samples at once, remains to be studied in acquired cholesteatoma. In this study, 16 consecutive patients from January 2020 to January 2021 at the Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU) were reviewed. We detected a total of 31 microbial species in patients, mNGS provided a higher detection rate compared to culture (100% vs. 31.25%, p = 0.000034). As the severity of the patient’s pathological condition worsens, the more complex types of microbes were identified. The most commonly detected microbial genus was Aspergillus (9/16, 56.25%), especially in patients suffering from severe bone erosion. In summary, mNGS improves the sensibility to identify pathogens of cholesteatoma patients, and Aspergillus infections increase bone destruction in acquired cholesteatoma.

Fenestral Otosclerosis: A Subtle Lesion Easily Missed

A 29-year-old Filipina of Chinese descent presented with progressive bilateral conductive hearing loss of several years’ duration. While working overseas, she consulted with an otolaryngologist and underwent computerized tomographic (CT) imaging of the temporal bone as part of her evaluation. She was informed that no abnormalities were identified in the imaging exam, and she was offered exploratory middle ear surgery with possible stapes surgery. She then sought a second opinion, with the intention of obtaining a more definitive diagnosis prior to any invasive medical intervention. A review of the CT imaging study, with particular emphasis on looking for radiologic evidence of otosclerosis, revealed the presence of a focal region of bone demineralization in the region of the fissula ante fenestram. (Figure 1) This finding is consistent with a diagnosis of fenestral otosclerosis.
 
 Otosclerosis is one of the main differential diagnoses for a patient presenting with bilateral conductive hearing loss and no other visible evidence of otologic disease. Although it is more common in the Caucasian population,1 it must remain as one of the considerations in the Asiatic population, including Filipinos. High-resolution CT is the imaging technique of choice in the evaluation of conductive hearing loss.2 When evaluating a scan for evidence of otosclerosis, it must be remembered that the most common location of involvement is the bone just anterior to the oval window, in a small cleft known as the fissula ante fenestram. It is this relationship that gives rise to the term fenestral otosclerosis. The fissula is a thin fold of connective tissue extending through the endochondral layer, located in the region between the oval window and the cochleariform process, where the tensor tympani tendon turns laterally toward the malleus.3 (Figure 2) Since the average length of the stapes footplate along its short axis is around 1.5 mm, it is highly recommended that submillimeter image slice thickness be routinely ordered for the CT imaging study, in order to maximize the opportunity to identify the oftentimes small and subtle areas of focal demineralization. At a slice thickness of 0.5 mm, such a lesion might only be identified by an astute clinician in 2-3 sequential axial imaging slices.

Conductive hearing loss after surgical treatment of otosclerosis - long-term observations.

<b>Introduction:</b> For many years, surgical treatment of otosclerosis has been a widely accepted approach. Hearing improvement following stapes surgery is sometimes spectacular, and good treatment results are obtained in many centers in over 90% of patients. However, in the subsequent years after the treatment, some patients develop permanent or progressive conductive hearing loss. <br><b>Aim:</b> The aim of the study is to present a group of patients with conductive hearing loss after the first otosclerosis surgery and to analyze the causes of its occurrence. <br><b>Materials and Methods:</b> The retrospective review covered patients who underwent the initial surgery in the years 2000-2009. We analyzed the patients' medical records from before the end of 2019, which provided results of at least 10 years of postoperative follow-up. The group consisted of 1118 patients aged 14-82, including 802 women and 316 men.<br><b> Results:</b> Reoperations due to conductive hearing loss were performed on 93 patients, who accounted for 8.3% of the originally operated patients. They were much more common in patients after stapedectomies (19.7%) than in patients after stapedotomy (5.5%). Prosthesis dislocation was found to be the most frequent intraoperative observation (44.1%) and was often associated with erosion or necrosis of the long process of incus (28%). Less frequent reasons for hearing loss were: adhesions around the prosthesis (10.8%), too small hole in the stapes footplate (8.6%), too short prosthesis (8.6%), progression of otosclerosis (7.5%), too long prosthesis (6.4%), presence of a granuloma around the prosthesis (5.4 %), and displacement of incus (4.3%). <br>Conclusions:</b> Surgical treatment of otosclerosis is a widely accepted and good method. It allows to achieve an improvement in hearing in the vast majority of patients treated in this way. Unfortunately, over the years some patients develop recurrent conductive hearing loss. Reoperation creates an opportunity for finding the cause and improving hearing in the majority of cases.

Isolated Incudostapedial Cholesteatomas: Unique Radiologic and Surgical Features

Congenital cholesteatomas originate from epithelial tissue present within the middle ear in patients with an intact tympanic membrane, no history of otologic surgery, otorrhea, or tympanic membrane perforation. They are diagnosed by a pearl-like lesion on otoscopy and computed tomography (CT) scan showing an expansile soft-tissue mass. We describe a series of patients with no prior otologic history presenting with progressive unilateral conductive hearing loss and normal otoscopy. The CT scans showed ossicular erosion without obvious soft-tissue mass. Surgery confirmed incudostapedial erosion found to be cholesteatoma. In this study, we characterize the clinical course of patients diagnosed with isolated incudostapedial cholesteatoma (IIC) and review possible pathologic mechanisms. Retrospective review of IIC cases treated by the Department of Pediatric Otolaryngology, Rady Children's Hospital, San Diego, 2014 to 2020. Data included patient demographics, clinical features, imaging, surgical findings, and audiologic data. Five patients were diagnosed with IIC (3 [60%] female; mean age at presentation 10.7 years [range 5.5-16.0]). All patients presented with postlingual unilateral conductive hearing loss and normal otoscopy without any past otologic history; delay in diagnosis ranged from 4 months to several years. The CT scans showed ossicular chain erosion with an absent long process of the incus and/or stapes superstructure. All patients underwent middle ear exploration, revealing a thin layer of cholesteatoma in the incudostapedial region, confirmed by histopathology. Mean preoperative speech reception threshold was 55 dB and improved to a mean of 31 dB in the 4 patients who underwent ossicular chain reconstruction. Isolated incudostapedial cholesteatoma should be included as a possible etiology in pediatric patients with insidious onset of unilateral conductive hearing loss with normal otoscopy, unremarkable otologic history, and a CT scan showing ossicular abnormality/disruption without notable middle ear mass. These patients should be counseled preoperatively regarding the possibility of cholesteatoma and should undergo middle ear exploration with possible ossiculoplasty.

Hearing Screening in Preschool Children of a Rural Community in Portugal - A 10-year Experience

Abstract Introduction Preschool hearing screening programmes would identify later onset or progressive hearing losses and conductive hearing loss, due to the high prevalence of otitis media with effusion in childhood. Hearing loss associated with otitis media with effusion can have a great impact on reading, writing, central auditory processing and balance. Objectives The present study aims at characterising the audiological alterations found in preschool children screened in a rural community in Portugal, and the correlation between audiological findings and otoscopy. Methodology This is an observational study using the results obtained in a ten year audiological and otological screening of preschool children. Otoscopy, Tympanometry and Audiometry (1, 2 and 4 KHz presented at 40 and 20 dB intensity) were performed at the first stage of the screening and the results were classified as “pass” or “refer”. Every non-normal result of any category would imply a second stage consisting of observation by an ENT specialist at the site and the establishing of a follow-up plan. Written Informed Consent was obtained from the parents prior to initiating the study. Results 595 children aged 5 and 6 years were screened between 2007 and 2017, of whom 192 (32.3%) required referral to the second stage. The most frequent alteration was found in the tympanogram. The tympanograms showed a significant correlation with the otoscopy performed by the ENT doctor, mainly type B tympanograms. The pass/refer audiometry also showed a statistically significant correlation with the medical otoscopy, although weak in all frequencies studied. Conclusion It’s extremely important to perform a hearing screening in the age range of 5-6 years (with a high predisposition to middle ear problems), with the main objective of identifying and referring for treatment children who present alterations in order to reduce the consequences of the hearing impairment.

Otosclerosis Revisited

Introduction: Otosclerosis usually manifests as a progressive conductive or mixed hearing loss occurring clinically to varying degrees in 0.5% - 1% of the general population. Stapedectomy /stapedotomy is the current treatment of choice for conductive component of Otosclerosis.
 Materials and Methods: Sixty patients attending the department of ENT of a Medical College Hospital in Bangalore between October 2012 and October 2017 were included in the study.
 Results: The incidence of otosclerosis is highest in the 3rd and 4th decade. Bilateral symptoms were present in 25% and 75% had unilateral symptoms, right side being more common in our study. Tinnitus and vertigo with deafness are seen in 60% and 25 % of the patients respectively.
 Ninety percent of the patients presented with moderate to moderately severe hearing loss. Twenty four (40%) out of 60 audiograms studied showed Carhart's notch. Postoperativeclosure of a-b gap to within 10dB could be achieved in 65% cases. The p value calculated comparing pre and post op results is <0.0001 and significant.
 Vertigo was found to be most common post-operative complication (35%) followed by sensorineural hearing loss (6.6%). Other complications observed during the study include - tympanic membrane tears, foot plate extrusion, lax long process of incus, perilymph leak.
 Conclusion: From the assessment of the postoperative hearing gain and postoperative complications, it can be concluded that small fenestra stapedotomy gives satisfactory post-operative outcome and may be appropriatein the Indian scenario.

Adenomatous Neuroendocrine Tumors of the Middle Ear: A Multi-institutional Investigation of 32 Cases and Development of a Staging System.

To date, less than 150 cases of middle ear adenomatous neuroendocrine tumors (MEANTs) have been reported in the English literature. The objective of this study was to provide a contemporary analysis of these rare lesions and develop a consensus-driven staging system. Multi-institutional retrospective histopathologic, radiologic, and clinical review. Six tertiary referral centers. Thirty-two patients with pathologically confirmed MEANT. Surgical resection, adjuvant therapy. Clinical manifestations, outcomes, staging system. Patients commonly presented with progressive conductive or mixed hearing loss (90%), aural fullness (50%), and tonal tinnitus (46%). Pulsatile tinnitus (16%), carcinoid syndrome (4%), and facial nerve paresis (4%) were less commonly observed. MEANTs frequently mimicked temporal bone paraganglioma (31%) and cholesteatoma (15%) at presentation. According to a novel T/N/M/S staging system (S = secretory tumor) proposed herein, there were 6 (19%) T1, 19 (59%) T2, and 7 (22%) T3 MEANTs. T3 tumors were significantly more likely to undergo subtotal or near total resection compared with lower staged tumors secondary to adherence to critical neurovascular structures such as the petrous internal carotid artery and facial nerve (p = 0.027). Patients with T3 MEANTs were more likely to experience multiple recurrences, require adjuvant therapy with a somatostatin analogue, or develop permanent facial nerve paresis compared with lower staged tumors. At last follow up, no patients with T1 MEANTs had developed recurrence, whereas 37% (7/19) of patients with T2 MEANT and 57% (4/7) of patients with T3 MEANT experienced either disease recurrence after gross total resection (GTR) or regrowth of known residual tumor requiring additional surgery at a median duration of 72 months (95% CI, 24-84). Patients with MEANTs can present with nonspecific symptomatology that overlaps with more commonly encountered middle ear lesions. MEANT exhibits a proclivity for recurrence according to T-stage and long-term clinical follow up is necessary, particularly for advanced stage tumors.

Degree of tinnitus improvement with stapes surgery - a review.

IntroductionOtospongiosis is temporal bone osteodystrophy, characterized by disordered bone resorption and neoformation in genetically predisposed individuals. Clinically, otospongiosis is characterized by progressive conductive and/or mixed hearing loss and by tinnitus.ObjectiveA review of the last two decades of publications that report the degree of tinnitus improvement with stapes surgery.Methods125 articles published in the last 20 years mentioning the relationship between otosclerosis and tinnitus. Literature has always shown that the hearing improvement after stapes surgery was the main result sought and found. However, recent articles has reinforced the need for surgery for the tinnitus improvement. The ideal time to assess tinnitus through different scales is in the sixth month post-operative. The estimated average hearing improvement is 93% and tinnitus is 85.52%.ResultsSummaries of 12 articles were reviewed which fulfilled the search criteria of the survey, and 8 studies were included in the study according the selection criteria. This studies investigating the degree of tinnitus improvement with stapes surgery, using different scales as: tinnitus functional index, visual analog scale, tinnitus functional index and visual analog scale, visual analog scale and “questionnaire asking about tinnitus”, Newman's method and Tinnitus Score Advocated by the Japan Audiological Society. The total of the samples of the evaluated articles was of 254 participants.ConclusionWe conclude that stapes surgery is effective for the treatment of tinnitus (average improvement is 85.52%), and hearing loss (average improvement is 93%). When deciding about the surgical indication in patients with otosclerosis, the presence and level tinnitus should be considered as well as the level of hearing.

Risk of progressive hearing loss in untreated superior semicircular canal dehiscence.

Patients with incidental or minimally symptomatic superior semicircular canal dehiscence (SSCD) are usually observed, without surgical repair. However, it remains unknown whether a labyrinthine fistula of the superior semicircular canal is associated with progressive conductive or sensorineural hearing loss over time. Retrospective review at two tertiary care academic referral centers. Adults analyzed were diagnosed with SSCD by high-resolution temporal bone computed tomography and vestibular evoked myogenic potential testing and observed with a minimum of two sequential audiograms. Patients with other potential causes of hearing impairment were excluded. A total of 40 ears in 30 adult patients (median age: 59 years; 63% female) were analyzed. Median audiometric follow-up was 23 months (range 1-136 months). None experienced a sudden hearing loss over the follow-up period. In patients with audiometric follow-up of at least 20 months (median 34 months), the median change in air-conduction pure tone average and air-bone gap was 0.9 decibels (dB) per year (interquartile range [IQR] 0-2.1) and 0.7 dB per year (IQR 0-2.0), respectively. Speech discrimination scores did not differ when comparing median initial (100%) and median final (98%) scores (P = 0.77). There was no statistically significant change in bone-conduction thresholds at 0.5, 1, 2, and 4 kHz over the period of observation. The risk of progressive hearing loss with observed SSCD is low during short- and intermediate-term follow-up. Further studies are necessary to determine whether late hearing loss occurs. Such information may be critical toward patient counseling regarding the need for and timing of surgery. 4. Laryngoscope, 127:1181-1186, 2017.

Update on the imaging diagnosis of otosclerosis

Otosclerosis is a primary osteodystrophy of the temporal bone that causes progressive conductive hearing loss. The diagnosis is generally clinical, but multidetector CT (MDCT), the imaging technique of choice, is sometimes necessary. The objective of this article is to systematically review the usefulness of imaging techniques for the diagnosis and postsurgical assessment of otosclerosis, fundamentally the role of MDCT, to decrease the surgical risk.

Actualización en el diagnóstico radiológico de la otosclerosis

Otosclerosis is a primary osteodystrophy of the temporal bone that causes progressive conductive hearing loss. The diagnosis is generally clinical, but multidetector CT (MDCT), the imaging technique of choice, is sometimes necessary. The objective of this article is to systematically review the usefulness of imaging techniques for the diagnosis and postsurgical assessment of otosclerosis, fundamentally the role of MDCT, to decrease the surgical risk.

Teflon Implants Versus Titanium Implants in Stapes Surgery.

Otosclerosis is the most common cause of bilateral gradually progressive conductive hearing loss with normal tympanic membrane and Eustachian tube. Otosclerosis surgical treatment is one of the most gratifying operations in Otorhinolaryngology. It is not only the surgical techniques but also the prosthesis which are evolving in the attempt of providing best hearing results. Teflon piston is the most commonly employed prosthesis in stapes surgery. Titanium pistons are relatively the new development in the evolution of stapes prosthesis. The aim of this review article is to know and compare the surgical technicalities and postoperative outcomes including hearing improvement after the use of Teflon and titanium stapes piston. The adverse reactions occurred during follow-up were taken into consideration. The data in this article are supported by a Medline search. The use of both the prosthesis gave good results in cases of otosclerosis. The placement of titanium soft clip design was found easier than the earlier àWengen design of clip piston.

Disrupted Bone Remodeling Leads to Cochlear Overgrowth and Hearing Loss in a Mouse Model of Fibrous Dysplasia

Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG) that can prevent cochlear bone remodeling. Accordingly, diseases that affect bone regulation can also result in hearing loss. Patients with fibrous dysplasia develop trabecular bone overgrowth resulting in hearing loss if the lesions affect the temporal bones. Unfortunately, the mechanisms responsible for this hearing loss, which could be sensorineural and/or conductive, remain unclear. In this study, we used a unique transgenic mouse model of increased Gs G-protein coupled receptor (GPCR) signaling induced by expression of an engineered receptor, Rs1, in osteoblastic cells. These ColI(2.3)+/Rs1+ mice showed dramatic bone lesions that histologically and radiologically resembled fibrous dysplasia. We found that ColI(2.3)+/Rs1+ mice showed progressive and severe conductive hearing loss. Ossicular chain impingement increased with the size and number of dysplastic lesions. While sensorineural structures were unaffected, ColI(2.3)+/Rs1+ cochleae had abnormally high osteoclast activity, together with elevated tartrate resistant acid phosphatase (TRAP) activity and receptor activator of nuclear factor kappa-B ligand (Rankl) mRNA expression. ColI(2.3)+/Rs1+ cochleae also showed decreased expression of Sclerostin (Sost), an antagonist of the Wnt signaling pathway that normally increases bone formation. The osteocyte canalicular networks of ColI(2.3)+/Rs1+ cochleae were disrupted and showed abnormal osteocyte morphology. The osteocytes in the ColI(2.3)+/Rs1+ cochleae showed increased expression of matrix metalloproteinase 13 (MMP-13) and TRAP, both of which can support osteocyte-mediated peri-lacunar remodeling. Thus, while the ossicular chain impingement is sufficient to account for the progressive hearing loss in fibrous dysplasia, the deregulation of bone remodeling extends to the cochlea as well. Our findings suggest that factors regulating bone remodeling, including peri-lacunar remodeling by osteocytes, may be useful targets for treating the bony overgrowths and hearing changes of fibrous dysplasia and other bony pathologies.

Bilateral schwartze sign, decision-making for surgery.

Otosclerosis is an otic capsule disorder that leads to progressive conductive and/or sensorineural hearing loss due to stapes footplate fixation and cochlear bone involvement. The disorder is bilateral in 70% of patients and it usually starts between the third and fifth decade. One of its characteristic clinical findings is Schwartze sign which refers to a reddish discoloration over the promontory seen beyond the intact tympanic membrane. Schwartze sign, also known as Flemingo's flush sign or Rising sun sign is believed to be associated with otospongiosis which is the active phase of the disease. The prevalence of Schwartze sign is estimated to be 10%. The prevalence of bilateral sign has not been reported, but it is presumed to be too low. Herein, we introduce a patient with bilateral positive Schwartze sign. A twenty two year old woman with bilateral hearing loss came to our clinic. She also complained from non pulsating tinnitus in both ears since one year ago. On physical examination, bilateral schwartze sign with an intact tympanic membrane was noted (Fig.1). The audiometric evaluation showed a conductive hearing loss with speech reception threshold of 50 dB and 30 dB for the right and left ear respectively. Sodium fluoride 8mg every 8 hours was prescribed for three months. She noticed partial improvement during the treatment and on her otoscopic exam, the Schwartze sign was reduced. Then stapedotomy was scheduled for the right ear (the worse ear in regard to the hearing & tinnitus). The surgery went uneventful and she proved to be much better afterwards. Her right ear tinnistus has gone completely and the speech reception threshold has changed from 45 dB preoperatively to 10 dB postoperatively. It seems that the surgery remains a therapeutic option, when the active phase of the disease is stabilized even following a short course of pharmacologic therapy.

Undiagnosed Severe Cochlear Otosclerosis as a Cause of Profound Hearing Loss

Otosclerosis is a disease of the human otic capsule1. Otosclerosis is well known to the otologist, as it is the most common cause for progressive conductive hearing loss in early adulthood. As hearing loss progresses, a sensorineural component is sometimes seen, resulting in a mixed hearing loss. In 1% of cases the disease is considered purely cochlear, presenting with a sensorineural hearing loss only, as the otosclerosis involves areas other than the footplate1.

The Brittle Cornea Syndrome: Study of a family with five affected siblings

AbstractPurpose To define the natural history,genotype‐phenotype correlation and differential diagnosis of the Brittle Cornea Syndrome (BCS),or Ehlers Danlos Syndrome (EDS) type VIB,caused by mutations in ZNF469 and PRDM5Methods We evaluated one family in which 5 out of 8 siblings suffered from BCS. We performed complete eye and systemic evaluations of the siblings and their parents. We sequenced the candidate gene,ZNF469Results On ocular evaluation we found keratoglobus and thinned corneas that tended to perforate spontaneously,as well as refractive errors caused by high myopia and irregular astigmatism. Progressive thinning of the corneas with keratoglobus led to visual deterioration due to spontaneous perforations and scarring. K readings were above 60 D and corneal thickness below 300um in 4 eyes that had not developed perforation. Systemic manifestations included joint hypermobility,increased elasticity of the skin but no cigarette paper scars, kyphoscoliosis,and progressive conductive hearing loss. Cardiovascular disease was not observed.The systemic findings overlap the kyphoscoliotic type of EDS VIA,the ocular manifestations of which consist of flattened corneal curvatures,fluid vitreous,radial perivascular lattice. Patients with BCS are often diagnosed as having the Marfan syndrome,even though spontaneous perforation of the cornea is not a feature of the latter condition. A 14bp insertion was found in exon 2 of ZNF469Conclusion EDS VIB is a connective tissue disease referred to as BCS; it is characterized by keratoglobus,thinned corneas and Marfanoid body habitus. Two causative genes for BCS have been identified to date,ZNF469 and PRDM5. A 14bp insertion was found in exon 2 of ZNF469. It is possible to provide genetic counseling in the extended family