Syndromic Hearing Loss: A Brief Review of Common Presentations and Genetics

AbstractCongenital hearing loss is one of the most common birth defects worldwide, with around 1 in 500 people experiencing some form of severe hearing loss. While over 400 different syndromes involving hearing loss have been described, it is important to be familiar with a wide range of syndromes involving hearing loss so an early diagnosis can be made and early intervention can be pursued to maximize functional hearing and speech-language development in the setting of verbal communication. This review aims to describe the presentation and genetics for some of the most frequently occurring syndromes involving hearing loss, including neurofibromatosis type 2, branchio-oto-renal syndrome, Treacher Collins syndrome, Stickler syndrome, Waardenburg syndrome, Pendred syndrome, Jervell and Lange-Nielsen syndrome, Usher syndromes, Refsum disease, Alport syndrome, MELAS, and MERRF.

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A novel case of concurrent occurrence of demyelinating-polyneuropathy-causing PMP22 duplication and SOX10 gene mutation producing severe hypertrophic neuropathy

BMC Neurology ◽

10.1186/s12883-021-02256-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nozomu Matsuda ◽

Koushi Ootsuki ◽

Shunsuke Kobayashi ◽

Ayaka Nemoto ◽

Hitoshi Kubo ◽

...

Keyword(s):

Hearing Loss ◽

Neuromuscular Disorders ◽

Whole Body ◽

Congenital Hearing Loss ◽

Severe Phenotype ◽

Demyelinating Neuropathy ◽

Magnetic Resonance Neurography ◽

Peripheral Myelin Protein 22 ◽

Hypertrophic Neuropathy

Abstract Background Hereditary motor and sensory neuropathy, also referred to as Charcot–Marie–Tooth disease (CMT), is most often caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. This duplication causes CMT type 1A (CMT1A). CMT1A rarely occurs in combination with other hereditary neuromuscular disorders. However, such rare genetic coincidences produce a severe phenotype and have been reported in terms of “double trouble” overlapping syndrome. Waardenburg syndrome (WS) is the most common form of a hereditary syndromic deafness. It is primarily characterized by pigmentation anomalies and classified into four major phenotypes. A mutation in the SRY sex determining region Y-box 10 (SOX10) gene causes WS type 2 or 4 and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease. We describe a 11-year-old boy with extreme hypertrophic neuropathy because of a combination of CMT1A and WS type 2. This is the first published case on the co-occurrence of CMT1A and WS type 2. Case presentation The 11-year-old boy presented with motor developmental delay and a deterioration in unstable walking at 6 years of age. In addition, he had congenital hearing loss and heterochromia iridis. The neurological examination revealed weakness in the distal limbs with pes cavus. He was diagnosed with CMT1A by the fluorescence in situ hybridization method. His paternal pedigree had a history of CMT1A. However, no family member had congenital hearing loss. His clinical manifestation was apparently severe than those of his relatives with CMT1A. In addition, a whole-body magnetic resonance neurography revealed an extreme enlargement of his systemic cranial and spinal nerves. Subsequently, a genetic analysis revealed a heterozygous frameshift mutation c.876delT (p.F292Lfs*19) in the SOX10 gene. He was eventually diagnosed with WS type 2. Conclusions We described a patient with a genetically confirmed overlapping diagnoses of CMT1A and WS type 2. The double trouble with the genes created a significant impact on the peripheral nerves system. Severe phenotype in the proband can be attributed to the cumulative effect of mutations in both PMP22 and SOX10 genes, responsible for demyelinating neuropathy.

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Neurofibromatosis: part 2 – clinical management

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20150042 ◽

2015 ◽

Vol 73 (6) ◽

pp. 531-543 ◽

Cited By ~ 3

Author(s):

Pollyanna Barros Batista ◽

Eny Maria Goloni Bertollo ◽

Danielle de Souza Costa ◽

Lucas Eliam ◽

Karin Soares Gonçalves Cunha ◽

...

Keyword(s):

Clinical Management ◽

Clinical Manifestations ◽

Neurofibromatosis Type ◽

Cutaneous Manifestations ◽

Wide Range ◽

Reduced Rate ◽

Present Text

Part 1 of this guideline addressed the differential diagnosis of the neurofibromatoses (NF): neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH). NF shares some features such as the genetic origin of the neural tumors and cutaneous manifestations, and affects nearly 80 thousand Brazilians. Increasing scientific knowledge on NF has allowed better clinical management and reduced rate of complications and morbidity, resulting in higher quality of life for NF patients. Most medical doctors are able to perform NF diagnosis, but the wide range of clinical manifestations and the inability to predict the onset or severity of new features, consequences, or complications make NF management a real clinical challenge, requiring the support of different specialists for proper treatment and genetic counseling, especially in NF2 and SCH. The present text suggests guidelines for the clinical management of NF, with emphasis on NF1.

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Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma

Journal of Clinical Oncology ◽

10.1200/jco.19.01367 ◽

2019 ◽

Vol 37 (35) ◽

pp. 3446-3454 ◽

Cited By ~ 13

Author(s):

Scott R. Plotkin ◽

Dan G. Duda ◽

Alona Muzikansky ◽

Jeffrey Allen ◽

Jaishri Blakeley ◽

...

Keyword(s):

Hearing Loss ◽

Growth Factor ◽

Phase Ii ◽

Standard Dose ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

High Dose ◽

Radiographic Response ◽

Bevacizumab Treatment

PURPOSE Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS. PATIENTS AND METHODS Bevacizumab was given for 6 months at 10 mg/kg every 2 weeks, followed by 18 months at 5 mg/kg every 3 weeks. The primary end point was hearing response defined by word recognition score (WRS) at 6 months. Secondary end points included toxicity, radiographic response, quality of life (QOL), and plasma biomarkers. RESULTS Twenty-two participants with NF2 (median age, 23 years) with progressive hearing loss in the target ear (median baseline WRS, 53%) were enrolled. Nine (41%) of 22 participants achieved a hearing response at 6 months (1 of 7 children and 8 of 15 adults; P = .08). Radiographic response was seen in 7 (32%) of 22 patients with VS at 6 months (7 of 15 adults and 0 of 7 children; P = .05). Common mild to moderate adverse events included hypertension, fatigue, headache, and irregular menstruation. Improvement in NF2-related QOL and reduction in tinnitus-related distress were reported in 30% and 60% of participants, respectively. Paradoxically, high-dose bevacizumab treatment was not associated with a significant decrease in free vascular endothelial growth factor but was associated with increased carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell-derived factor 1α, and basic fibroblast growth factor concentrations in plasma. CONCLUSION High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in QOL during induction. Novel approaches using bevacizumab should be considered for children with NF2.

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Establishment of nomograms for the prediction of useful hearing loss in patients with neurofibromatosis type 2

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03889-2 ◽

2021 ◽

Author(s):

Shi-wei Li ◽

Jing Zhang ◽

Han-lu Tang ◽

Peng Li ◽

Bo Wang ◽

...

Keyword(s):

Hearing Loss ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2

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A Complete Constellation of Nervous System Lesions of NF2: Imaging Evaluation

Case Reports in Radiology ◽

10.1155/2012/353179 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4

Author(s):

Kiran Gangadhar ◽

Sandeep Kumar ◽

Lovekesh Bhatia ◽

Arjit Agarwal

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Hearing Loss ◽

Neurofibromatosis Type ◽

Radiological Findings ◽

Case Patient ◽

Cutaneous Lesions ◽

Imaging Evaluation ◽

The Central Nervous System

The radiological findings fulfilling the criteria of neurofibromatosis type 2 (NF2) were reviewed. NF2 is a rare disease with few cutaneous but frequent, typical radiological findings in the central nervous system. The presenting symptom is most commonly hearing loss due to acoustic schwannomas, although symptoms emanating from other intracranial or tumors are not uncommon. The discovery of multiple spinal neurofibromas or multiple meningiomas without cutaneous lesions should initiate a search for acoustic schwannomas even when the patient has normal hearing as in our case patient who actually presented for weakness of all four limbs.

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The Birmingham bone anchored hearing aid programme: paediatric experience and results

The Journal of Laryngology & Otology ◽

10.1017/s0022215100136230 ◽

1996 ◽

Vol 110 (21) ◽

pp. 21-29 ◽

Cited By ~ 35

Author(s):

R. H. Powell ◽

S. P. Burrell ◽

H. R. Cooper ◽

D. W. Proops

Keyword(s):

Hearing Loss ◽

Otitis Media ◽

Hearing Aid ◽

Treacher Collins Syndrome ◽

Chronic Suppurative Otitis Media ◽

Congenital Hearing Loss ◽

Suppurative Otitis Media ◽

Subjective Data ◽

Bone Anchored Hearing Aid

AbstractOver a five-year period, 34 patients have been referred to the Birmingham bone anchored hearing aid programme, paediatric section, of whom 21 are now wearing the bone anchored hearing aid (BAHA) and four are awaiting surgery for fitting of the BAHA. Of the patients assessed, found to be suitable and who proceeded to surgery for the BAHA, 44 per cent had Treacher Collins syndrome, 28 per cent had bilateral atresia or microtia, 16 per cent had Goldenhaar's syndrome, four per cent (one patient) had branchio-oto-renal syndrome and eight per cent had chronic suppurative otitis media. This paper presents objective and subjective data collected from these patients. It is shown that the BAHA is a very effective hearing aid for children with congenital hearing loss.

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Age at Onset and Presenting Symptoms of Neurofibromatosis Type 2 as Prognostic Factors for Clinical Course of Vestibular Schwannomas

Cancers ◽

10.3390/cancers12092355 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2355

Author(s):

Isabel Gugel ◽

Florian Grimm ◽

Julian Zipfel ◽

Christian Teuber ◽

Ulrike Ernemann ◽

...

Keyword(s):

Hearing Loss ◽

Clinical Course ◽

Age At Onset ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Vestibular Schwannomas ◽

Speech Discrimination ◽

Predictive Values ◽

Presenting Symptoms

The presenting symptoms of the tumor suppressor gene syndrome neurofibromatosis type 2 (NF2) are often non-specific and unrelated to the disease hallmark bilateral vestibular schwannomas (VS). However, age at onset and presenting symptoms may have predictive values for the clinical course of VS. In this retrospective single-center study, we addressed this issue by reviewing 106 patients with 194 VS. Presenting symptoms attributable to VS commonly occur in 87% of adults and 31% of children. Age at onset significantly correlates with tumor volumes at presentation (p = 0.034). In addition, age at onset significantly correlates with pure-tone average (p = 0.0001), speech discrimination scores (p = 0.001), age at beginning of hearing loss (p = 0.0001), age at deafness (p = 0.0001), and age at first surgery (p = 0.0001). Patients presenting with VS related symptoms had significantly (p < 0.05) worse hearing values at presentation and after surgery. These patients also exhibited higher growth rates and tumor volumes compared to patients with non-VS related presenting symptoms, but this difference did not reach the significance level of p < 0.05. Due to the late appearance of these symptoms, the time of beginning hearing loss, surgery and deafness is significantly delayed (p < 0.05) compared to patients not presenting with VS. In summary, age at onset and type of presenting symptom provide excellent prognostic parameters for predicting VS- and hearing-related clinical course.

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Family with neurofibromatosis type 2 and autosomal dominant hearing loss: identification of carriers of the mutated NF2 gene

Human Genetics ◽

10.1007/bf00214177 ◽

1995 ◽

Vol 96 (1) ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

E. K. Bijlsma ◽

P. Merel ◽

P. Fleury ◽

C. J. van Asperen ◽

A. Westerveld ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Dominant ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Nf2 Gene

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Internal Auditory Canal Decompression for Hearing Maintenance in Neurofibromatosis Type 2 Patients

Neurosurgery ◽

10.1227/neu.0000000000001125 ◽

2015 ◽

Vol 79 (3) ◽

pp. 370-377 ◽

Cited By ~ 7

Author(s):

Daniele Bernardeschi ◽

Matthieu Peyre ◽

Michael Collin ◽

Mustapha Smail ◽

Olivier Sterkers ◽

...

Keyword(s):

Hearing Loss ◽

Internal Auditory Canal ◽

Neurofibromatosis Type ◽

Early Postoperative Period ◽

Neurofibromatosis Type 2 ◽

Hearing Level ◽

Speech Discrimination ◽

Unilateral Deafness

Abstract BACKGROUND: In neurofibromatosis type 2 (NF2), multiple therapeutic options are available to prevent bilateral hearing loss that significantly affects the quality of life of patients. OBJECTIVE: To evaluate the morbidity and functional results of internal auditory canal (IAC) decompression in NF2 patients with an only hearing ear. METHODS: Twenty-one NF2 patients operated on for IAC decompression in a 3-year period with a minimum follow-up of 1 year were included in this retrospective study. They presented unilateral deafness due to previous contralateral vestibular schwannoma removal in 16 patients or contralateral hearing loss due to the tumor in 5 patients. Hearing level was of class A (American Academy of Otolaryngology-Head and Neck Surgery classification) in 7 patients, B in 8 patients, C in 1 patient, and D in 5 patients. Pure-tone average and speech discrimination score evaluations were performed at 6 days, 1 year, and during the follow-up. Eight patients had postoperative chemotherapy. RESULTS: No case of facial nerve palsy was observed. In the early postoperative period; all patients maintained the hearing class of the preoperative period. At 1-year follow-up, all but 3 patients maintained their hearing scores; at last follow-up (mean follow-up, 23 + 8 months; range, 12-44 months), hearing classes remained stable with only 1 patient worsening from class B to C and 1 patient improving from class D to B. CONCLUSION: Decompression of IAC seems to be a useful procedure for hearing maintenance in NF2 patients, with very low morbidity. Ideal timing and association with chemotherapy should be evaluated in the future.

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