Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder

Pathogenic variants in the PJVK gene cause the DFNB59 type of autosomal recessive non-syndromic hearing impairment (AR-NSHI). Phenotypes are not homogeneous, as a few subjects show auditory neuropathy spectrum disorder (ANSD), while others show cochlear hearing loss. The numbers of reported cases and pathogenic variants are still small to establish accurate genotype-phenotype correlations. We investigated a cohort of 77 Spanish familial cases of AR-NSHI, in whom DFNB1 had been excluded, and a cohort of 84 simplex cases with isolated ANSD in whom OTOF variants had been excluded. All seven exons and exon-intron boundaries of the PJVK gene were sequenced. We report three novel DFNB59 cases, one from the AR-NSHI cohort and two from the ANSD cohort, with stable, severe to profound NSHI. Two of the subjects received unilateral cochlear implantation, with apparent good outcomes. Our study expands the spectrum of PJVK mutations, as we report four novel pathogenic variants: p.Leu224Arg, p.His294Ilefs*43, p.His294Asp and p.Phe317Serfs*20. We review the reported cases of DFNB59, summarize the clinical features of this rare subtype of AR-NSHI and discuss the involvement of PJVK in ANSD.

Childhood hearing impairment and fertility in Norway

There is a lack of studies assessing how hearing impairment relates to reproductive outcomes. We examined whether childhood hearing impairment (HI) affects reproductive patterns based on longitudinal Norwegian population level data for birth cohorts 1940–1980. We used Poisson regression to estimate the association between the number of children ever born and HI. The association with childlessness is estimated by a logit model. As a robustness check, we also estimated family fixed effects Poisson and logit models. Hearing was assessed at ages 7, 10 and 13, and reproduction was observed at adult ages until 2014. Air conduction hearing threshold levels were obtained by pure-tone audiometry at eight frequencies from 0.25 to 8 kHz. Fertility data were collected from Norwegian administrative registers. The combined dataset size was N = 50,022. Our analyses reveal that HI in childhood is associated with lower fertility in adulthood, especially for men. The proportion of childless individuals among those with childhood HI was almost twice as large as that of individuals with normal childhood hearing (20.8% vs. 10.7%). The negative association is robust to the inclusion of family fixed effects in the model that allow to control for the unobserved heterogeneity that are shared between siblings, including factors related to the upbringing and parent characteristics. Less family support in later life could add to the health challenges faced by those with HI. More attention should be given to how fertility relates to HI.

Recurrent Bilateral Lower Motor Neuron Type of Facial Palsy with Hearing Impairment: Hyperphosphatemic Familial Tumoral Calcinosis

Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg2/mL2) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in FGF23 gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.

Speech-Driven Facial Animations Improve Speech-in-Noise Comprehension of Humans

Understanding speech becomes a demanding task when the environment is noisy. Comprehension of speech in noise can be substantially improved by looking at the speaker’s face, and this audiovisual benefit is even more pronounced in people with hearing impairment. Recent advances in AI have allowed to synthesize photorealistic talking faces from a speech recording and a still image of a person’s face in an end-to-end manner. However, it has remained unknown whether such facial animations improve speech-in-noise comprehension. Here we consider facial animations produced by a recently introduced generative adversarial network (GAN), and show that humans cannot distinguish between the synthesized and the natural videos. Importantly, we then show that the end-to-end synthesized videos significantly aid humans in understanding speech in noise, although the natural facial motions yield a yet higher audiovisual benefit. We further find that an audiovisual speech recognizer (AVSR) benefits from the synthesized facial animations as well. Our results suggest that synthesizing facial motions from speech can be used to aid speech comprehension in difficult listening environments.

Surgical treatment of glossopharyngeal nerve schwannomas: Results of two-center study (14 patients included) and literature review

Objective: This study is aimed to analyze the outcomes of surgical treatment of glossopharyngeal schwannomas based on pre- and postoperative neurological status assessment. Materials and methods: This paper is a retrospective analysis of examination and surgical treatment of 14 patients who were operated on in two large clinics from 2018 to 2021 inclusive. When analyzing the collected data, gender, age, disease symptoms, tumor size and location, surgical approach, tumor to cranial nerves (CN) ratio, jugular foramen (JF) condition, and tumor removal volume were taken into account. All tumors were divided into groups depending on tumor location relative to the JF. Particular attention was paid to assessing cranial nerves functions. Facial nerve function was assessed as per House-Brackmann Scale (HBS), hearing function as per Gardner-Robertson Scale (GRS). Results: 3 (21.4%) patients had total tumor removal: 2 patients had type A tumors and one had type B tumor. Subtotal resection took place in 7 (50%) cases. In 4 cases, a tumor was partially removed: 3 patients had type D tumors and one had type B tumor. 3 (21.4%) patients had preoperative FN deficit (HBS Grade II) and mild dysfunction. 5 (35.7%) patients had postoperative facial nerve deficit: HBS ІІ, 2; ІІІ, 1; V, 2. Preoperative sensorineural type hearing impairment on the affected side was diagnosed in 13 (92.6%) patients. Before surgery, 6 patients had non-serviceable hearing, which remained at the same level after surgery. None of the patients with grade I or II hearing before surgery had any hearing impairment postoperatively. In 2 (14.3%) cases, hearing improved from grade V to grade III after surgery. 6 (42.9%) patients developed new neurological deficit in the caudal group CN. Postoperative deficit of the caudal group CN occurred in type D tumors in 3 patients, type A tumors 2 patients, and type B tumors one patient. Conclusions: Applying a retrosigmoid approach only makes it possible to achieve total tumor removal in case of type A tumors. To remove other tumor types, it is necessary to select approaches that enable access to the jugular foramen and infratemporal fossa. Intraoperative neurophysiological monitoring is an extremely important tool in glossopharyngeal schwannoma surgery. The most common postoperative complication is a developed or increased deficit of the caudal CN group, which can lead to persistent impairments in the patients’ quality of life. Preservation of the CN VII and VIII function in most cases is a feasible task and shall be ensured as a standard for this pathology.

Como me Tornei um Estudante Universitário, apesar das Limitações da Deficiência Auditiva Bilateral / How I Became a College Student Despite the Limitations of Bilateral Hearing Impairment

Resumo: Esse artigo é baseado no relato pessoal de um estudante, de Pedagogia, com deficiência auditiva bilateral, dando ênfase aos desafios e superações da pessoa com deficiência no ambiente educacional. Ademais, o presente texto aborda as principais características da deficiência auditiva e suas dificuldades no Ensino Tradicional. Segundo o Instituto Brasileiro de Geografia e Estatística (IBGE), em 2020, cerca de 10 milhões de pessoas apresentavam deficiência auditiva, representando 5% da população brasileira. Além disso, é possível observar que existem causas biológicas que determinam diferentes níveis de audição, que impactam, diretamente, no desenvolvimento psicossocial e na interação social. De acordo com uma revisão de artigo da deficiência auditiva de alterações genéticas ou mutações no DNA mitocondrial, foi possível observar que, a grande maioria das pessoas com deficiência auditiva apresenta essa condição por causas genéticas. Nesse contexto, será contada a trajetória de um estudante de Pedagogia, desde o Ensino Fundamental até o Ensino Superior. Será ressaltado como o teatro mudou completamente sua vida e será mostrado como esse pensamento foi construído apesar das dificuldades de ouvir. Nesse âmbito, a pessoa com deficiência auditiva precisa mostrar as principais barreiras que dificultam sua interação social, promovendo inclusão, identificando crianças com deficiência auditiva e proporcionando estratégias pedagógicas e empoderando sua identidade. Além disso, minha experiência sendo pessoa com deficiência auditiva será essencial para ser futuramente um educador com deficiência auditiva. Apesar das limitações, é possível aprender e educar. Vale destacar a importância da pessoa com deficiência auditiva na formação do professor, motivando outras pessoas com deficiência como também as pessoas que não possuem nenhuma deficiência.Palavras-chaves: Deficiência auditiva, ambiente educacional e fonética. Abstract: This article is based on the personal report of a student of Pedagogy, with bilateral hearing loss, emphasizing the challenges and overcoming of people with disabilities in the educational environment. Furthermore, this text addresses the main characteristics of hearing loss and its difficulties in Traditional Education. According to the Brazilian Institute of Geography and Statistics (IBGE), in 2020, around 10 million people had hearing loss, representing 5% of the Brazilian population. Furthermore, it is possible to observe that there are biological causes that determine different levels of hearing, which directly impact psychosocial development and social interaction. According to a review of an article on hearing loss due to genetic alterations or mutations in mitochondrial DNA, it was possible to observe that the vast majority of people with hearing loss have this condition due to genetic causes. In this context, the trajectory of a Pedagogy student will be told, from Elementary School to Higher Education. It will highlight how theater completely changed his life and it will be shown how this thought was built despite the difficulties of hearing. In this context, the person with hearing impairment needs to show the main barriers that hinder their social interaction, promoting inclusion, identifying children with hearing impairment and providing pedagogical strategies and empowering their identity. Furthermore, my experience as a person with a hearing impairment will be essential to being a future hearing impaired educator. Despite the limitations, it is possible to learn and educate. It is worth highlighting the importance of the person with hearing impairment in teacher training, motivating other people with disabilities as well as people who do not have any disability.Keywords: Hearing impairment, educational and phonetic environment.