Since Carlo Mondini observed the phenomenon of enlarged vestibular aqueduct in the temporal bone of an 8-year-old boy with congenital deafness in the eighteenth century, by the 1960s Valvassori found enlarged vestibular aqueducts in 160 patients during imaging of more than 7000 consecutive patients, almost all of whom had sensorineural deafness and vestibular symptoms, reporting for the first time the The Menière-like clinical phenotype associated with the vestibular aqueduct was first reported. By 1978, Valvassori and Clemis et al. identified 50 enlarged vestibular aqueducts in 3700 patients with auditory or vestibular dysfunction on multitrack tomography of the temporal bones and named them “large vestibular aqueduct (LVA)”. The enlarged vestibular aqueduct was also found to be associated with sensorineural hearing loss and was officially named the large vestibular aqueduct syndrome. Subsequently, in 1989, Jackler et al. retrospectively studied the clinical features of 17 patients with enlarged vestibular aqueduct only and emphasized the importance of separating patients with enlarged vestibular aqueduct only with hearing loss from those with enlarged vestibular aqueduct with other inner ear malformations and proposed the theory of progressive or stepwise hearing loss in patients with large vestibular aqueduct. In the same year, Levenson et al. proposed the concept of “isolated LVAS” for patients with only enlarged vestibular aqueduct and sensorineural deafness, and in 1995, Okumura et al. formally proposed to divide LVAS into two types: LVAS with cochlear malformation and LVAS without cochlear malformation. In 1996, Griffith et al. identified siblings with LVAS and hypothesized that the disease might be autosomal recessive. 1999, Abe and Usami et al. localized the LVAS-related gene at 7q31 and found that it was associated with the SLC26A4 gene in this region, opening up a new era of LVAS genetic research. This opened a new era of genetic research on LVAS. Today, in the 21st century, scholars in China have made a series of meaningful explorations in this area of understanding LVAS, discovering the specific mutation profile of LVAS in the Chinese population, proposing a systematic diagnostic process for clinical diagnosis of LVAS, carrying out clinical genetic diagnosis and prenatal diagnosis of LVAS, and conducting intra-aural scientific treatment of LVAS. We have carried out the clinical genetic diagnosis and prenatal diagnosis of large vestibular aqueduct syndrome, and the treatment of large vestibular aqueduct syndrome in intra-aural science. Therefore, the authors have written this article to discuss and consider the strategies to improve the clinical detection and diagnosis of vestibular aqueduct syndrome, and to make some suggestions and thoughts around this disease. 1. There is a high prevalence of vestibular aqueduct syndrome disease in China, and there is an urgent need to improve the ability to detect and diagnose vestibular aqueduct syndrome disease. Due to the rapid progress of hereditary deafness research in recent years, the understanding of large vestibular aqueduct syndrome disease has gradually reached a new height. Vestibular aqueduct syndrome is a common hearing disorder that accounts for 1-12% of sensorineural hearing loss and varies greatly in frequency by race. The frequency of mutations in the causative SLC26A4 gene in patients with large vestibular aqueduct syndrome was found to vary by ethnicity: Prasad et al. detected the mutation in only 30% of European LVAS patients, while Tsukamoto et al. found that 78.1% of 32 Japanese LVAS patients had the mutation; Park et al. et al. showed that the SLC26A4 gene mutation was detected in 92.3% of Korean LVAS patients. In China, Yali Zhao et al. found that 97.9% of patients with middle LVAS had mutations in this gene. So, what is the prevalence of large vestibular aqueduct syndrome disease in the deaf population? In a survey of deaf schools, 13-16% of patients with large vestibular aqueduct syndrome were found to be deaf. If we count 2780 people with hearing and speech impairment in China, 3.61-4.44 million deaf patients are patients with large vestibular aqueduct syndrome, and the work to identify all patients has not yet been done, so it is not yet known how many such patients exist in China, and their offspring still have a 25% or higher chance of reoccurrence. On the other hand, with the widespread development of newborn hearing screening in China, there are more than 30,000 newborn deaf children in China, and if about 13-16% of them are patients with large vestibular aqueduct syndrome, 3900-4800 new patients with large vestibular aqueduct syndrome should be diagnosed every year. There are 23,000 otorhinolaryngologists in China, so how many of them have the expertise to diagnose vestibular aqueduct syndrome? In recent years, I have been engaged in the research of hereditary deafness and specialized in the diagnosis, treatment and consultation of deafness in children, and so far I have only diagnosed more than 800 patients with the syndrome. So, are new patients diagnosed and counseled in a timely manner every year nationwide? It should be said that it is far from enough. A large number of patients are underdiagnosed, neglected and do not receive timely and effective counseling and rehabilitation, which is an important reason for the rising number of students in deaf schools. Therefore, in the face of the high prevalence characteristics of patients with large vestibular aqueduct syndrome in China, there is an urgent need to improve the consensus and awareness of peers to detect and diagnose large vestibular aqueduct syndrome disease. 2. How to detect the disease of large vestibular aqueduct syndrome in the implementation of newborn hearing screening work. In 2000, our government affirmed the significance and necessity of conducting newborn hearing screening in the form of the Maternal and Child Health Law of the People’s Republic of China. Hearing screening of newborns has been widely carried out nationwide, which has laid the basic conditions for early detection of children with hearing loss. However, it is a matter of concern if those patients with large vestibular aqueduct syndrome are detected during newborn hearing screening? Large vestibular aqueduct syndrome (LVAS) is a hearing disorder characterized by enlargement of the vestibular aqueduct and sensorineural or mixed hearing loss, which can develop at any age from birth to adolescence. The onset of hearing loss can be sudden or insidious and is often preceded by a cold, fever, minor cranial trauma, pneumatic trauma, or other causes of increased intracranial pressure; hearing loss is progressive and gradual over a long period of time, ranging from near normal to profound deafness, with asymmetric hearing in both ears. One of the most important features of vestibular canal syndrome is that it is congenital but can develop later in life; it is genetic but can be associated with environmental trauma and external factors such as colds; it is a sensorineural hearing loss but can be characterized by low frequency conductive hearing loss. Due to the characteristics of these changes, it is difficult and challenging to detect and diagnose large vestibular canal syndrome in neonates and infants. (1) Some children with large vestibular aqueduct syndrome may show a “pass” in neonatal hearing screening, but hearing impairment is found with growth and development. The reason for this may be closely related to the anatomical features of the embryonic development of the vestibular aqueduct. The vestibular aqueduct occurs during the fourth and fifth weeks of embryonic development and shows continuous nonlinear growth throughout the embryonic period, with similar growth curves for the medial, lateral, midpoint, and length of the vestibular aqueduct. Kodama et al. studied the postnatal development of the vestibular canal and endolymphatic sac in children aged 0 to 13 years and concluded that the pattern of changes in the vestibular canal and endolymphatic sac was as follows: in the first year of life, the vestibular canal and endolymphatic sac were small in the wrinkled part and grew In the first year of life, the vestibular canal and endolymphatic sac are small and grow slowly. Therefore, many parents have not been able to detect the problem of hearing changes in their children. Therefore, newborns who pass the initial newborn hearing screening still need to be rescreened and followed up. If deafness is in the family, the child is at high risk and should undergo combined newborn hearing and genetic screening. (2) Some children with large vestibular aqueduct syndrome present with a “fail” on newborn hearing screening and subsequent diagnostic testing shows mild to moderate hearing loss. Hearing results that show “failure” at both initial (OAE) and repeat (OAE+AABR) newborn screening should be taken very seriously. If a mild to moderate hearing loss is identified at 3 months of age, there are several possibilities for clinical diagnosis: a. Mild to moderate hearing loss due to neurodevelopmental delay, which can be recovered subsequently; b. Infantile secretory otitis media, which has the potential to heal spontaneously; c. Permanent sensorineural hearing loss, which is irreversible; and d. Large vestibular canal syndrome, which has fluctuating and progressive hearing loss. fluctuate and progressive decline, etc. Among these common hearing loss disorders, the diagnosis of large vestibular canal syndrome is easily overlooked in infancy and early childhood, especially in children with mild to moderate hearing loss. The reason for this is that in infants and toddlers between 3 and 6 months of age, parents complain that the child is responsive to sound, and there are sometimes contradictions between the parents’ descriptions and the hearing test results; furthermore, CT scans are not recommended as mandatory in infants and toddlers during this period, so the treatment and rehabilitation of mild to moderate hearing loss is mainly based on waiting and family intervention. So, how to detect a child with large vestibular aqueduct syndrome? A combined audiogenetic screening of the newborn is one way to do this. If the hearing screen is not passed, a genetic screen for heterozygous or compatible with heterozygosity for SLC26A4 as well as pure heterozygosity is highly suggestive of large vestibular aqueduct syndrome. An abnormal negative waveform ASNR (acous. tically evoked short latency negative response, ASNR) on ABR is highly suggestive of large vestibular aqueduct syndrome. If necessary, a CT scan of the child can reveal enlarged vestibular canals. (3) Some children with large vestibular aqueduct syndrome present with a “fail” newborn hearing screening, and subsequent diagnostic hearing tests show severe hearing loss. The diagnosis is usually very severe sensorineural deafness. Not only is a high-resolution CT scan performed, but MRI of the internal auditory canal water is also desirable. One side misses the diagnosis of large vestibular aqueduct syndrome or malformation disease of the inner ear. (4) Combining newborn hearing screening with deafness susceptibility gene screening can detect suspected children at the first time: newborn deafness susceptibility gene screening refers to the concept of incorporating deafness susceptibility gene screening at the molecular level based on the widely conducted newborn hearing screening and performing newborn umbilical cord blood or heel blood collection at birth or within 3 days after birth to screen for deafness susceptibility and common genes. In March 2007, based on a large number of previous studies on deafness genetics combined with clinical newborn hearing screening, the authors found that simple hearing screening does have major shortcomings, and therefore were the first in China to advocate the introduction of genetic screening in newborn hearing screening. Therefore, the new concept of genetic screening was firstly advocated in China, and the combined newborn hearing and genetic screening model was firstly explored in the international arena. In ten provinces and cities in China (Beijing, Gansu, Guangxi, Guangdong, Hunan, Hubei, Yunnan, Fujian, Liaoning, Xinjiang), 14,343 newborns were screened for combined hearing and deafness susceptibility genes. The cumulative positive carrier rate is 20.2‰. These hidden genes are the bottleneck of deafness prevention and control in China, and the only way to detect deafness patients and high-risk groups is to conduct combined hearing and genetic screening in newborns. Therefore, through the combined model of newborn hearing and genetic screening, firstly, drug-sensitive deaf individuals are identified, which cannot be detected in conventional hearing screening; secondly, deaf patients are detected and diagnosed earlier. The combined hearing and genetic screening will bring forward this time to within 7 days of birth and avoid the interference of uncertainties, thus improving the efficiency of diagnosis. This new screening model will undoubtedly elevate newborn hearing screening to a new level! 3.Popularize the knowledge of large vestibular canal syndrome disease among marriageable couples. The popularization of the knowledge of the disease of large vestibular canal syndrome among couples of marriageable age can further advance the warning time of large vestibular canal syndrome, which can not only minimize the impact on the language development of children with large vestibular canal syndrome, but also avoid the birth of children with large vestibular canal syndrome. When a hearing couple has a child with Vestibular Patience Syndrome, the chances of them having a child with the same condition are 25%, with equal chances for both sexes, and a 50% chance of having a child with the same mutation as the parents, and a 25% chance of having a child with normal hearing. Therefore, it is important to spread awareness of the greater vestibular aqueduct syndrome among couples of marriageable age. For couples with no family history of deafness hearing normal marriage couples are tested for this gene to find out if they are carriers; for couples with a family history of deafness, especially those who have had a child with large vestibular aqueduct syndrome, they need to be tested for this gene mutation and genetic counseling is provided through prenatal diagnosis to prevent the birth of an affected child. 4. How to screen for patients with large vestibular aqueduct syndrome disease in schools for the deaf. Deaf students are a large group that needs more care and attention to help them return to social life. About 13-16% of the pre-deaf students are caused by the mutation of the gene of the large vestibular aqueduct syndrome, which shows that the deaf patients with large vestibular aqueduct syndrome have a relatively high proportion of deaf students. The detection of SLC26A4 gene mutation in deaf students in deaf schools can make the diagnosis of large vestibular aqueduct syndrome at the molecular level, and thin layer temporal bone CT can further clarify the clinical diagnosis. Although the majority of deaf students have severe hearing loss or more, further definitive diagnosis for them is still of great importance. Because of the special circumstances and conditions often seen in marriages between deaf patients, and the percentage of children born who are deaf is significantly higher than normal. A marriage between two patients with a large vestibular aqueduct will produce children who will all be patients with a large vestibular aqueduct. If a marriage between a patient with a large vestibular aqueduct and a non-patient with a large vestibular aqueduct, the likelihood of having a deaf child is reduced, and with genetic counseling prenatal diagnosis, a child with normal hearing can be conceived. Therefore, SLC26A4 genetic screening test among students in deaf schools can effectively guide future marriages of these deaf students and target guidance to conceive a normal hearing newborn, thus reducing the incidence of deaf population. 5. To develop the ability to rapidly detect and diagnose the disease of large vestibular aqueduct syndrome among clinical professionals. Current advances in research on the greater vestibular aqueduct syndrome prove that the diagnosis of the disease has entered a new phase. This is marked by the development of a systematic diagnostic process that combines characteristic clinical audiological findings with imaging and mutational testing of the causative genes. Through this diagnostic process, clinicians can use the following ideas to detect and diagnose the disease, which can help to detect large vestibular plumbing disease at all levels of hospitals with different conditions: (1) First, pure tone hearing or behavioral audiometry, which can reveal low frequency “conductive hearing loss” in 70-80% of patients with normal middle ear function “This hearing curve cannot be explained by classical conductive deafness due to middle ear abnormalities in the external ear, but is snail “conductive deafness”. When this low-frequency hearing air-bone conduction difference is found, the diagnosis of large vestibular aqueduct syndrome should be considered. (2) The presence of an abnormal negative wave – ASNR – in 76% of patients during routine ABR testing is particularly important because this negative wave is elicited under the conditions of routine ABR testing, which is emphasized because the ASNR can be elicited in normal subjects when the test parameters are changed, whereas the ASNR found during routine ABR testing has 76% may suggest the presence of an enlarged vestibular aqueduct in the patient. (3) Imaging: Although advances in clinical audiology and genetic studies are important in the diagnosis of large vestibular aqueduct syndrome, imaging remains the current gold standard for the diagnosis of enlarged vestibular aqueduct. The understanding of the greater vestibular aqueduct syndrome has evolved with the development of imaging. Current imaging tests include high-resolution CT (HRCT) examination of the temporal bone and nuclear magnetic examination (MRI) of the temporal bone. These two examinations are the gold standard for diagnosing enlarged vestibular canal: enlarged vestibular canal is diagnosed when the diameter of the common pedicle of the semicircular canal to the outer orifice 1/2 of the vestibular canal is greater than 1.5 mm. (4) Genetic examination: The large vestibular aqueduct syndrome caused by the mutation of SLC26A4 gene is an autosomal recessive disease. Carriers of the SLC26A4 mutation, i.e., heterozygotes, usually have no clinical symptoms, and the mutated gene is silently inherited until two carriers combine, when their offspring may show symptoms; recessive disorders often occur in families of consanguineous parents, especially when the mutation is rare; when the frequency of a mutation in a population is very high, a patient and a carrier have an increased chance of combining, and their children may When the frequency of a mutation is very high in the population, the combination of a patient and a carrier increases the chance that the child may also be a patient, making the disease appear in two consecutive generations and showing pseudodominant inheritance. Therefore, it is important to analyze the audiological and genetic results to advise and guide the future and offspring of the patient. Conclusion: The high prevalence of vestibular aqueduct syndrome in China and the presence of a large number of patients with vestibular aqueduct syndrome in newborns, children and deaf schools requires an urgent improvement in the level of care provided by professionals. It is recommended to strengthen the learning and updating of new knowledge and new practice, to publicize the characteristics and diagnostic points of the large vestibular aqueduct syndrome, and to improve the overall understanding of the disease and the intervention and guidance of treatment for all professionals.