Sensorineural hearing loss is one of the important characteristics associated with mitochondrial DNA (mtDNA) mutation. A mtDNA mutation at position 3243 in the tRNALeu (UUR) gene has been found to be associated both with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and with maternally inherited diabetes mellitus and sensorineural hearing loss. In this article, we briefly summarize mitochondrial genetics including maternal inheritance, heteroplasmy, a threshold effect and molecular genetic differences between mtDNA and nuclear DNA, which will be helpful for understanding the mitochondrial diseases. We also present a detection of the 3243 mutation and audiologic characteristics in patients with hearing loss associated with the mutation. Some patients had cochlear characteristics and the other showed signs suggestive of retrocochlear involvement. We hypothesized that the expression of either cochlear or retrocochlear involvement is determined by the threshold effect in the inner ear and central auditory pathway in each cases.
Nonsyndromic genetic deafness is divided into conductive or mixed deafness and sensorineural deafness. The former is mainly comprised of middle ear malformations. Almost all familial cases of middle ear malformations are compatible with autosomal dominant inheritance. The sensorineural form of nonsyndromic genetic deafness is divided according to the mode of inheritance: dominant, recessive, X-linked or mitochondrial. Some genes of nonsyndromic deafness are mapped on chromosomes. Three or four genes are mapped on X chromosome. Familial occurrence of strepromycin-induced deafness was first reported about forty years ago. Since then some pedigrees of streptomycin-induced deafness have been noted. In 1979 we discovered a peculiar mode of inheritance, inferred to be caused by alterations of mitochondrial DNA. Later, apoint mutation at base pair 1555 of mitochondrial DNA was found. Recently we detected this mutation responsible for the aminglyconside-induced deafness easily by using restriction fragment length polymorphism (RFLP). We found 1555 mutations also in a case of sensorineural hearing loss of unknown origin. This means that this mutation also probably causes the hearing loss in cases other than aminoglycoside-induced deafness.
The purpose of the Human Genome Project is to determine the complete genetic information carried in the human genome. This information will then be used to improve the quality of human life. Molecular cytogenetics techniques, including fluorescence in situ hybridization (FISH), chromosome-microdissection-painting method and comparative genome hybridization (CGH), are extremely useful tools for clinical genetics and research for human genome project.
Patterns of symptoms in the auditory system were clinically investigated among 26patients with ‘CATCH 22’ syndrome treated in th e Department of Otolaryngology of Tokyo Women's Medical College between March 1994 and September 1995. Chromosome analysis performed by means of the FISH technique at the Department of Pediatric Cardiology, showed a deletion within chromosome 22 qll in all cases. Typical facial appearance of CATCH22, such as ocular hypertelorism, lateraldisplacement of the inner canthi, narrow eye fissures, puffy eye lids, flat nasal bridge and small mouth was found in all cases. Auricular anomaly was shown most consistently. It was present in 20 cases, or 76.9% of the patients. Half of the 20 cases with auricular anomaly showed lop ear, with their helix folded forward and drooping like rabbit ears. There were 7 satyr ears in 4 cases, 2 macacus ears in l case and 7 other anomalous ears in 6 cases. The frequency of otitis media including acute otitis media and otitis media with effusion was approximately80%, but in most cases the degree was not severe. Conductive hearing loss was observed in 10 cases (38.5%), 5 were bilateral and 5 were unilateral. The severitywas mostly mild. There were neither sensorineural hearing loss nor mixed hearingloss. CT findings of the temporal bone were characterized by dilatation of eustachian tube (15.8%), aplasia or hypoplasia of the lateral semicircular canal (36.8%) and enlargement of the vestibule (36.8%). Caloric nystagmus test on ENG was done in 5 cases. There was no response to caloric stimulation in 4 cases including 2 cases had severe and 2 had moderatecanal paresis. Auditory dysplasia inCATCH22 syndrome was found in the external, middle or innerears. Auricular anomaly was present in 80%, dilatation of eustachian tube in 15% and the vestibular dysplasia in 35%. There was one familial transmission in a mother and her son. The rest of thecases was sporadic.
Waardenburg syndrome is characterized by dystopia canthorum, pigmentary disturbances and sensorineural deafness. This disorder is inherited in an autosomal dominant mode with incomplete penetrance and variable expression. The human paired-box homeotic gene 3 (PA3)3, a candidate for Waardenburg syndrome type I (WS I) was isolated by means of the rapid amplification of cDNA ends (RACE) procedure. Fluorescence in situ hybridization using a cosmid clone containing PAX3 as a probe demonstrated that the gene is located to chromosome 2q35. Analysis of gene expression in various human adult tissues by reverse transcriptase-based polymerase chain reaction (RT-PCR) revealed tissue-specific expression of this gene. A 684-bp transcript was generated only from the cerebellum and skeletal muscle by alternative splicing. Analysis of 17 WS families by PCR-SSCP and subsequent sequencing revealed that in one family, affected members had a point mutation, A to T transversion, which leads to an Ile to Phe substitution at codon 59.Another family had an A to T transversion, at the splice acceptor site at the intron 1-2 boundary. The gene product of PAX3 is a transcription factor that is active in early embryogenesis. However, little has been known about the target gene (s) of the product. Although several different mutations in PAX3 have been reported in WS I patients, no relationship was demonstrated between individual PAX3 mutations and particular clinical phenotypes. This unusual phenomenon in WS I may be explained by “haploinsufficiency with dosagesensitivity”: different tissues show differential sensitivity to the dose of PAX3 gene product. Alternatively, the phenomenon is due to dominant negative effect of the mutant gene.
Autoinflation therapy using a rubber balloon reported by Stangerup et al. was applied to 74 ears of 47 pediatric patients with secretory otitis media, resultingin improvement of tympanograms in 73% of the ears. There were no serious complications except for acute otitis media at a rate of 0.46 times per ear per year. However, there were 22 ears of recurrence. Our findings indicate that the thrapyusing a balloon is efficacious in the treatment of secretory otitis media in children.
Hearing results of 130 ears operated on by type III tympanoplasty were reviewed. Postoperative air-bone gap was less than 10dB in 70 ears (53.8%) and less than 20dB in 105 ears (80.8%). There was no statistical difference in hearing results between chronic middle otitis with and without cholesteatoma. There was statistical difference in mean postoperative air-bone gap between the cases used ossicles and the cases used cortical temporal bone chips (Post-hoc test, p<0.05).
From 1992 to 1994, at Osaka Saiseikai Izuo hospital, 24 tympanoplasties with stage operation were performed. Subjects were 15 ears suffering from otitis media with cholesteatoma and 9 ears with adhesion. The average duration was 9.2 months from the first tympanoplasty to the second stage surgery, and follow-up study was made in 6 to 40 months after the second operation. Bone pate which is mixed bone powder and fibrin glue, auricular cartilage, cortical bone and Guilford flap as a reconstruction material for the external auditory canal wall were investigated. There was no recurrence of cholesteatoma and otorrhea. The incidence of deformation of the auditory canal was 16.6%. The prostheses was fitted 100% in the case with bone pate, 88.2% with cartilage and none with cortical bone. Histopathological findings in bone pate specimens from the second look operation showed bone tissues with osteoid tissue structure forming spongy bone contained fibrous stroma. For the reconstruction of the canal wall defect, bone pate, cartilage, cortical bone and Guilford flap are either useful materials because are viable autograft receiving blood supply via the periosteal pedicle and well adapted into the surrounding tissues. This technique is effective for the reconstruction of the canal wall defect after canal down procedure.
Recently, incidence of acute mastoiditis decreased markedly, but we experienced five cases of acute mastoiditis over the last three years. The five, patients presented with various clinical courses; findings, symptoms, and/or treatments. The diagnosis of the acute mastoiditis was made based on individual findings and symptoms. Especially, computed tomography of mastoid could play a reliable role to make the diagnosis. Acute mastoiditis with cholesteatoma should be treated more carefully, because cholesteatoma could often extended to the intracranial area. However, acute mastoiditis was not necessarily treated by surgical intervention in the first choice. Five patients in this report had different treatments including conservative tretment according to each clinical course.
Traumatic perilymphatic fistula due to an earpick producing luxation of the stapesinto the vestibuleis extremely rare. A 20-year-old male presented with severe vertigo and hearing loss in the right side after he used an earpick which injured the ear drum. Traumatic perilymphatic fistula was suspected. Two weeks later, vertigo and sensorineural hearing loss were almost improved but mild dizziness and conductive hearing loss were still remained. Exploratory tympanotomy was performed under general anesthesia, and the dislocated stapes into the vestibule was found. A strut of auricular cartilage was placed between the stapes and the incus, and the piece of fascia temporalis was placed around the stapes. The postoperative course was satisfactory. The patient has been free from dizziness and hearing loss, and no recurrece was found to date.