Nueva aplicación móvil para categorización del vértigo en el nuevo milenio / New mobile application for categorization of vertigo in the new millennium

Introducción: El vértigo se define como la distorsión en la sensación de movimiento propio cuando se realiza un movimiento normal de la cabeza, para su estudio y categorización por el médico general, se recomienda el enfoque TiTrATE, que determina el momento de inicio, duración, evolución y los desencadenantes del vértigo. Objetivo: creación de una aplicación web progresiva (PWA) llamada TiTrATEapp y aplicarla en los pacientes que acudan a la emergencia en el mes de febrero 2023. Método: estudio tipo prospectivo, experimental, observacional, de análisis comparativo. Resultado: se creó una aplicación web progresiva (PWA) llamada TiTrATEapp, basada en el algoritmo TiTrATE, comparándose el tiempo de cálculo de la aplicación del algoritmo de forma manual y digital, obteniendo como resultado que la aplicación digital es más rápida y eficaz. Conclusión: Las aplicaciones móviles son una herramienta objetiva que ayuda los profesionales de la salud a diagnosticar y a tomar decisiones clínicas de forma práctica basadas en la evidencia científica, la digitalización del TiTrATE permite a los médicos realizar un diagnóstico acertado de forma rápida y orientan a la referencia del paciente a la especialidad correcta y la eficiencia de recursos. (AU)

Introduction: Vertigo is defined as the distortion in the sensation of self-movement when a normal movement of the head is made, for its study the TiTrATEapproach is recommended for the general practitioner, which determines the moment of onset, duration, evolution and triggers of vertigo for its study and categorization accurately. Objective: to create a progressive web application (PWA) called TiTrATEapp, Method: Prospective, observational, longitudinal study. Result: creation of a progressive web application (PWA) called TiTrATEapp, based on the TiTrATE algorithm, comparing the calculation time of the application of the algorithm manually and digitally, resulting in the digital application being faster and more efficient. Discussion: Vertigo is a difficult symptom to decipher in the emergency room, due to the subjective description of patients and the wide variety of probable causes, the digitization ofTiTrATE allows to rule out potentially dangerous causes, quickly, accurately. At present there are no studies that measure the effectiveness of mobile applications for the study of vertigo. Conclusion: Mobile applications are an objective tool that helps health professionals diagnose and make clinical decisions in a practical way based on scientific evidence, the digitalization of TiTrATE allows resident doctors to make an accurate diagnosis quickly and guide the patient's referral to the correct specialty and resource efficiency. (AU)

Case report: Macrophage activation syndrome in a patient with Kabuki syndrome.

Macrophage activation syndrome (MAS), is a severe and fatal complication of various pediatric inflammatory disorders. Kabuki syndrome (KS), mainly caused by lysine methyltransferase 2D (KMT2D; OMIM 602113) variants, is a rare congenital disorder with multi-organ deficiencies. To date, there have been no reported cases of MAS in patients with KS. This report describes a case of a 22-year-old male with Kabuki syndrome (KS) who developed MAS. This unique case not only deepens the understanding of the involvement of KMT2D in immune regulation and disease, but expands the phenotype of the adult patient to better understand the natural history, disease burden, and management of patients with KS complicated with autoimmune disorders.

Hyperventilation-Induced Nystagmus in Acute Unilateral Vestibulopathy: A Correlation with Vestibulo-ocular Reflex Gain and Clinical Implication.

Hyperventilation-induced nystagmus test (HINT) is capable of generating a response in 77.2% of cases of acute unilateral vestibulopathy (AUVP); both nystagmus toward the affected side (excitatory pattern) and toward the healthy side (inhibitory pattern) have been described. The aim of the study is to investigate the clinical and prognostic role of the test by evaluating its correlation with vestibulo-ocular reflex (VOR) gain. We evaluated 33 AUVP patients by performing the HINT and video head impulse test (V-HIT) during the acute phase and then at 15 and 90 days after the onset of the symptoms. The correlation between the VOR gain of the affected side and test responses was evaluated first, phase by phase, and then considering the pattern shown during the first assessments. Patients with a negative HINT had a higher mean VOR gain than patients with a positive test at both 15 and 90 days. Patients who showed an inhibitory pattern at the first assessment had a continuous improvement in V-HIT performance, while patients with an initial excitatory response had a transient decrease in gain at the subsequent evaluation (P=.001). No difference between these 2 groups emerged at 90 days (P=.09). The finding of a negative HINT during the follow-up correlates with good V-HIT performance and could be an indicator of good recovery. The inhibitory pattern is associated with a subsequent improvement; and it would be indicative of compensation. but, despite this, the prognostic value of the test is limited.

[Cochleovestibular manifestations in coronavirus infection]. / Kokhleovestibulyarnye proyavleniya pri koronavirusnoi infektsii.

One of the main causes of the of the inner ear pathology is a viral infection including SARS-CoV-2 virus. On the other hand the psycho-emotional state of patients also affects patients with hearing loss, tinnitus and dizziness, and an increase in depression and anxiety was revealed during the period of self-isolation. Goal of our study was to analyze cochleovestibular pathology in patients with COVID-19. The study involved 84 patients and the leading complaint was hearing loss - in 70 patients, tinnitus - in 54 patients, dizziness - in 50 patients. In addition, an increased anxiety background was found in patients, as well as signs of depression. Thus, the 2020 pandemic period was a high risk period for patients with inner ear pathology, which may be associated not only with the actual pathological effect of the virus on the auditory and vestibular system, but also with changes in the psycho-emotional status of patients.

[Test-retest reliability of subjective visual vertical from different head-tilt angles in young healthy adults].

Objective:To establish the normal values of subjective visual vertical （SVV） in different head deflection angles and analyze its test and retest reliability, in order to provide a reference for the clinical application of SVV in the evaluation of vestibular disorders. Methods:Thirty-one healthy young people were selected to wear VR glasses, and the SVV data were tested in five different head-tilt, namely, 0° in the upright head position, 45°in the left head position, 45° in the right head position, 90° in the left head position, and 90° in the right head position, and were re-tested 2 weeks later. Results:①The mean values of SVV at 5 different head-tilt angles of 0°, left 45°, right 45°, left 90°, and right 90° were -0.07±1.71, 4.30±5.39, -6.51±5.58, -3.76±7.42, and 0.40±8.02, respectively, The 95% confidence limits of SVV at 0°, left 45°, right 45°, left 90°, right 90°, and right 90° were （-3.42, 3.28）, （-6.26, 14.86）, （-17.45, 4.43）, （-18.30, 10.78）, and（-15.32, 16.12）, respectively; ②The absolute values of SVV at 4 different head-tilt angles of left 45°, right 45°, left 90°, and right 90° were 5.62±3.96, 6.90±5.07, 6.82±4.70 and 6.48±4.68, respectively. The 95% confidence limits of SVV at left 45°, right 45°, left 90°, right 90°, and right 90° were（0，12.11）,（0，15.21）,（0，14.53）and（0，14.16）, respectively. The asymmetry ratio is 10% for the absolute value of the 45 ° deviation and 3% for the absolute value of the 90° deviation; ③Intra-class correlation coefficients（ICC） for 0°, left 45°, right 45°, left 90°, right 90°were 0.757, 0.673, 0.674, 0.815, and 0.856, respectively. Conclusion:SVV has good retest reliability and high stability, and the SVV normal value data of different head deviation angles established in the present study can be used as a reference for the diagnosis and evaluation of vestibular disorders.

Brazilian Version of the Vestibular Activities and Participation Measure: Cross-Cultural Adaptation, Validity, and Reliability.

BACKGROUND: Vestibular Activities and Participation Measure (VAP) subscales assess the effect of vestibular disorders on activity and participation. This study aimed to perform the cross-cultural adaptation and assess the validity, internal consistency, reliability, and measurement error of the Brazilian version of VAP subscales. METHODS: The cross-cultural adaptation followed the translation, synthesis, back-translation, review by a committee of experts, and pretesting phases. Structural validity was assessed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), while Spearman's correlation between VAP subscales and the Dizziness Handicap Inventory (DHI) was used to assess construct validity. Cronbach's alpha measured internal consistency. Intraclass correlation coefficient (ICC) assessed intra- and inter-rater reliability, and measurement error was calculated by using the standard error of measurement (SEM) and minimal detectable change (MDC). RESULTS: Additional information was included in the Brazilian version of the Vestibular Activities and Participation measure (VAP-BR) after approval by one of the developers of the instrument to improve the understanding among individuals. One factor was found in the EFA for each subscale with 50% explained variance. Regarding CFA, the subscales 1 (S1) and 2 (S2) presented, respectively, adequate model fit indices (ie, comparative fit index of 0.99 and 0.97, and standardized root mean square residual of 0.04 for both subscales), but a very low factor load in item 6 of S1 (0.08). Chronbach's alpha was 0.80 (S1) and 0.82 (S2). For intra-rater assessment, the S1 and S2 presented an ICC of 0.87 and 0.90, SEM of 0.01 and 1.16, and MDC of 0.39 and 0.46, respectively. When assessed by 2 different raters, SEM values were 1.03 and 1.53, and MDC values were 2.85 and 4.23 for S1 and S2, respectively; both subscales showed an ICC of 0.92. Correlations between DHI and VAP subscales presented coefficients above 0.57. CONCLUSION: The Brazilian version of VAP subscales presents good measurement properties and may assist health professionals in identifying activity limitations and participation restrictions in individuals with vestibular disorders.

Are Vestibuloocular Reflex Gain and Dynamic Visual Acuity Responsible of Oscillopsia After Complete Unilateral Vestibular Loss?

BACKGROUND: Acute and complete unilateral vestibular deafferentation induces a significant change in ipsilateral vestibuloocular reflex gain, making the patient unable to stabilize gaze during active or passive head movements. This inability creates the illusion that the visual environment is moving, resulting in persistent visual discomfort during rapid angular or linear acceleration of the head. This is known as oscillopsia. Our objective was to understand if the spontaneous sensation of oscillopsias after complete unilateral vestibular deafferentation by vestibular neurotomy at 5 days (D5) and at 3 months (M3) is correlated with the loss of vestibuloocular reflex gain and dynamic visual acuity. METHODS: Retrospective cohort study was conducted in an otolaryngology tertiary care center (2019-2022) on patients with complete unilateral vestibular loss by vestibular neurotomy. They were divided into 2 groups according to the presence (group G1) or absence (group G2) of a spontaneous complaint of oscillopsia assessed at M3. Severity of oscillopsias evaluated by Oscillopsia Severity Questionnaire. Vestibuloocular reflex gain based on video head impulse test (vHIT) and the dynamic visual acuity were measured for each group at D5 and M3. Categorical variables were compared using χ2 test and quantitative variables using the nonparametric Wilcoxon-Mann-Whitney test. RESULTS: All patients have a complete vestibular deafferentation at D5 and M3. At D5 (G1 = 8 patients, G2 = 5 patients), there is no significant difference for ipsilateral and contralateral vestibuloocular reflex gains and dynamic visual acuity losses. The Oscillopsia Severity Questionnaire was 2.68 ± 1.03 in G1 and 1.23 ± 1.03 in G2 (P < .05). At M3 (G1 = 9 patients, G2 = 6 patients), there is no significant difference between groups for epidemiologic and clinical data and for vestibuloocular reflex and dynamic visual acuity losses. The Oscillopsia Severity Questionnaire was 2.10 ± 0.63 in G1 and 1.24 ± 0.28 in G2 (P < .05). CONCLUSIONS: The spontaneous disabling sensation of oscillopsia after complete unilateral vestibular loss is well assessed by the Oscillopsia Severity Questionnaire but cannot be explained by objective vestibular tests assessing vestibuloocular reflex gain (vHIT) or dynamic visual acuity loss at D5 or M3. Further studies are needed to measure the sensation of oscillopsia under real-life conditions and to identify the factors responsible for its persistence. TRIAL REGISTRATION: Retrospectively registered.

[The VeSFADS structural classification of vestibular disorders].

The issuing of International Classification of Vestibular Disorders（ICVD） by Brny society（2015） greatly facilitates the progress of vestibular medicine. The syndromic classification of vestibular disorders by ICVD enable the physician to narrow the spectrum of differential diagnosis for the vestibular disorder in clinical practice. However, the division of vestibular pathway, especially the central vestibular system, has not be classified yet in the ICVD（2015）. Central vertigo, being a group of heterogeneous disorders, may present diverse clinical spectrums. The misdiagnosis of central vestibular as well as peripheral vestibular disorders have been reported in the clinic practice. Therefore, the author by review study proposes a structural classification of vestibular disorders combined the Vestibular System Functional Anatomy Division with Syndromes（VeSFADS）. The VeSFADS classification of vestibular disorders could help the physician in clinical practice to narrow the spectrum of vestibular disorders, in addition to the syndromic classification, by the clinical feature of vestibular disorders from different division of vestibular system. And the VeSFADS classification of vestibular disorders may facilitate to clarify the clinical features of vestibular disorders at different Division of vestibular pathway.

Clinical Assessment of the Nystagmus Fixation Suppression Test: An Experimental Study.

BACKGROUND:  Assessment of nystagmus fixation suppression can be used as an additional diagnostic tool for patients with an acute vestibular syndrome to distinguish between a central or peripheral cause. We investigated the ability of physicians to detect fixation suppression using a nystagmus simulation model. METHODS:  We used a nystagmus simulator to measure the accuracy of the nystagmus fixation suppression test. Fixation suppression was assessed randomly in 6170 trials by 20 otorhinolaryngologists and neurologists, segregated into 2 groups based on their neurootological experience, a beginner and an experienced group. The simulator presented random nystagmus slow velocity (SPV) reductions and presented 3 conditions with either changed nystagmus frequency, amplitude, or both. RESULTS:  The cutoff for the discernment of fixation suppression ranged from 1.2 to 14°/s nystagmus velocity difference. The more intense the baseline nystagmus was, the more difficult was the detection of fixation suppression. There was not significant difference (P >.05) in the cutoff values in the experts group compared to the novices for all 3 different conditions. Both, novices and experts, detected frequency changes easier than differences of the nystagmus amplitude. Test sensitivity was very low (19%-65%) for discernment of small nystagmus velocity differences of <2°/s by experts. CONCLUSION:  In our study, there was no difference between experts and novices in detection of nystagmus suppression by visual fixation. The examiners could only detect large suppression effects at low-intensity baseline nystagmus. Overall, the sensitivity and accuracy of a clinical fixation suppression test is low and the assistance with a video-oculography device is highly recommended.

Clinical experiences, current approaches, opinions and awareness of healthcare professionals regarding the audio-vestibular consequences of individuals with traumatic brain injury: a cross-sectional online survey study.

OBJECTIVE: To explore the experiences, current approaches, opinions and awareness of healthcare professionals (HCPs) caring for adults with traumatic brain injury (TBI) regarding the audio-vestibular consequences. DESIGN/SETTING: Cross-sectional online survey study. PARTICIPANTS: HCPs with experience of caring for adults with TBI, who were not ENT (ear nose throat) specialists or audiologists. METHODS: The study was conducted from May 2022 to December 2022. The online survey consisted of 16 closed and open-text questions in English and Turkish about clinical experience, current approaches and awareness of audio-vestibular consequences following TBI. Frequencies of responses to closed questions and associations between variables were analysed using SPSS V.28. Open-text responses were summarised in Microsoft Excel. RESULTS: Seventy HCPs participated from 17 professions and 14 countries, with the majority from the UK (42.9%). HCPs stated that 'some' to 'all' of their patients had auditory problems such as 'inability to understand speech-in-noise' (66%), 'tinnitus' (64%), 'hyperacusis' (57%) and balance problems such as 'dizziness' (79%) and 'vertigo' (67%). Usually, HCPs asked about the balance status of patients at appointments and when they observed dizziness and/or balance disorder they used screening tests, most commonly finger-to-nose (53%). For auditory impairments, HCPs preferred referring patients with TBI to audiology/ENT services. However, 6% of HCPs felt that audio-vestibular conditions could be ignored on referral because patients with TBI struggled with many impairments. Additionally, 44% would suggest hearing aids to patients with TBI with hearing loss 'if they would like to use' rather than 'definitely'. CONCLUSIONS: Many audio-vestibular impairments are observed by HCPs caring for patients with TBI. The assessment and intervention opinions and awareness of HCPs for these impairments vary. However, non-expert HCPs may not be aware of negative consequences of untreated audio-vestibular impairments following TBI. Therefore, developing a simple framework for screening and indications of audio-vestibular impairments for referral may be helpful for non-audiological specialists regularly seeing these patients.

Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.

Trithorax-related H3K4 methyltransferases, KMT2C and KMT2D, are critical epigenetic modifiers. Haploinsufficiency of KMT2C was only recently recognized as a cause of neurodevelopmental disorder (NDD), so the clinical and molecular spectrums of the KMT2C-related NDD (now designated as Kleefstra syndrome 2) are largely unknown. We ascertained 98 individuals with rare KMT2C variants, including 75 with protein-truncating variants (PTVs). Notably, ∼15% of KMT2C PTVs were inherited. Although the most highly expressed KMT2C transcript consists of only the last four exons, pathogenic PTVs were found in almost all the exons of this large gene. KMT2C variant interpretation can be challenging due to segmental duplications and clonal hematopoesis-induced artifacts. Using samples from 27 affected individuals, divided into discovery and validation cohorts, we generated a moderate strength disorder-specific KMT2C DNA methylation (DNAm) signature and demonstrate its utility in classifying non-truncating variants. Based on 81 individuals with pathogenic/likely pathogenic variants, we demonstrate that the KMT2C-related NDD is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, hypotonia, seizures, short stature, and other comorbidities. The facial module of PhenoScore, applied to photographs of 34 affected individuals, reveals that the KMT2C-related facial gestalt is significantly different from the general NDD population. Finally, using PhenoScore and DNAm signatures, we demonstrate that the KMT2C-related NDD is clinically and epigenetically distinct from Kleefstra and Kabuki syndromes. Overall, we define the clinical features, molecular spectrum, and DNAm signature of the KMT2C-related NDD and demonstrate they are distinct from Kleefstra and Kabuki syndromes highlighting the need to rename this condition.

Vestibular Migraine and Recurrent Vertigo in Children: A Diagnostic Focus From a Tertiary Hospital Study.

BACKGROUND: To improve diagnostic precision in pediatric vertigo, particularly in Vestibular Migraine of Childhood (VMC), probable VMC (pVMC), Recurrent Vertigo of Childhood (RVC), and unspecified categories, by delineating clinical characteristics and prevalence to refine diagnostics and treatments. METHODS: Retrospective analysis of 102 pediatric patients (five to 18 years; 46 females, 56 males) at the Dizziness Center of the Otolaryngology Department in a tertiary-level hospital from January 2019 to December 2023. Patients were classified into VMC, pVMC, RVC, and indeterminate groups. Evaluations included audiometry and vestibular tests (video head impulse test [vHIT] or caloric testing), conducted in the audiology unit and vestibular testing laboratory. Data were analyzed using IBM SPSS 20.0. RESULTS: Diagnoses were 8.8% VMC, 31.4% pVMC, 51.0% RVC, and 8.8% indeterminate. Nausea and vomiting were common in VMC and pVMC; cochlear symptoms like tinnitus and hearing loss predominated in VMC. Although vestibular testing showed no significant group differences, VMC had more vHIT abnormalities and RVC had more caloric test anomalies. CONCLUSIONS: This study highlights the need for comprehensive diagnostics in pediatric vestibular disorders, revealing unique and overlapping traits across VMC, pVMC, and RVC. Insights call for further research to refine diagnostic criteria and improve treatment methods.

Positional End-Point Nystagmus in Patients with Diagnosis of Acute Unilateral Vestibulopathy.

INTRODUCTION: Recently, end-point nystagmus, traditionally observed in an upright position, has been identified in the Dix-Hallpike position among healthy subjects, suggesting a physiological origin.However, its characteristics in individuals with vestibular hypofunction remain unexplored. OBJECTIVE: To elucidate the impact of vestibular hypofunction on the characteristics of positional end-point nystagmus. METHODS: Thirty-one patients diagnosed with acute unilateral vestibulopathy according to Bárány Society criteria were selected. A video head impulse test was conducted in all participants, followed by McClure and Dix-Hallpike maneuvers with and without gaze fixation, and with the initial position of the eye in the straight-ahead position or in the horizontal end-point position. Nystagmus direction, sense, latency, slow-phase velocity, and duration were recorded. The relationship between these characteristics and video head impulse test values was analyzed. RESULTS: Positional end-point nystagmus was observed in 92.6% of subjects with vestibular hypofunction, significantly more than in healthy individuals. Nystagmus direction varied depending on the performed positional test and on the vestibulo-ocular reflex gains. Gaze occlusion and the initial horizontal end-point position increased its frequency. CONCLUSION: Vestibular hypofunction influences the manifestation of positional end-point nystagmus. Recognizing this nystagmus can aid in resolving diagnostic uncertainties and preventing the misdiagnosis of benign paroxysmal positional vertigo in subjects with acute unilateral vestibulopathy.

[Advances in vestibular function and rehabilitation of large vestibular aqueduct syndrome].

Large vestibular aqueduct syndrome（LVAS） is a common recessive hereditary hearing loss disease, and some patients may also experience vestibular dysfunction. With the wide application of cochlear implant（CI） and the development of vestibular medicine, the pathophysiological mechanism of LVAS and the influence mechanism of CI on vestibular function are gradually elucidated. Consequently, the evaluation and rehabilitation of vestibular dysfunction function have also become research hotspots. This article reviews studies on vestibular function and related rehabilitation in patients with large vestibular aqueduct syndrome.

The altered functional status in vestibular migraine: A meta-analysis.

PURPOSE: Vestibular migraine (VM) is a disorder with prominent vestibular symptoms that are causally correlated with migraine and is the most prevalent neurological cause of episodic vertigo. Nevertheless, the functional underpinnings of VM remain largely unclear. This study aimed to reveal concordant alteration patterns of functional connectivity (FC) in VM patients. METHODS: We searched literature measuring resting-state FC abnormalities of VM patients in PubMed, Embase, Cochrane, and Scopus databases before May 2023. Furthermore, we applied the anisotropic effect size-signed differential mapping (AES-SDM) to conduct a whole-brain voxel-wise meta-analysis to identify the convergence of FC alterations in VM patients. RESULTS: Nine studies containing 251 VM patients and 257 healthy controls (HCs) were included. Relative to HCs, VM patients showed reduced activity in the left superior temporal gyrus and left midcingulate/paracingulate gyri, and increased activity in the precuneus, right superior parietal gyrus, and right middle frontal gyrus. Jackknife's analysis and subgroup analysis further supported the generalization and robustness of the main results. Furthermore, meta-regression analyses indicated that the Dizziness Handicap Inventory (DHI) ratings were positively correlated with the activity in the precuneus, while higher Headache Impact Test-6 and DHI scores were associated with lower activity within the left midcingulate/paracingulate gyri. CONCLUSIONS: The study indicates that VM is associated with specific functional deficits of VM patients in crucial regions involved in the vestibular and pain networks and provides further information on the pathophysiological mechanisms of VM.

Latent class analysis of migraine associated vestibular-auditory symptoms.

OBJECTIVE: This study aimed to identify the potential subgroups of migraines based on the patterns of migraine associated symptoms, vestibular and auditory symptoms using latent class analysis and to explore their characteristics. METHOD: A total of 555 patients with migraine participated in the study. Symptoms such as nausea, vomiting, photophobia, phonophobia, osmophobia, visual symptoms, vestibular symptoms (dizziness, vertigo), and auditory symptoms (tinnitus, hearing loss, aural fullness) were assessed. Latent class analysis was performed to identify subgroups of migraines. Covariates such as gender, age of migraine onset, frequency of migraine attacks per month, and family history were also considered. RESULTS: The analysis revealed four latent classes: the Prominent Vestibular; Prominent Nausea; Presenting Symptoms but not prominent or dominant; and Sensory Hypersensitivity groups. Various covariates, such as gender, age of migraine onset, and frequency of migraine attacks, demonstrated significant differences among the four groups. The Sensory Hypersensitivity group showed the presence of multiple sensory symptoms, earlier age of migraine onset, and higher proportion of females. The Prominent Vestibular group had the highest probability of dizziness or vertigo but lacked the presence of auditory symptoms. The Prominent Nausea group exhibited prominent nausea. The Presenting Symptoms but not prominent or dominant group comprised individuals with the highest migraine attacks per month and proportion of chronic migraine. CONCLUSION: This study identifies four subgroups of migraines based on the patterns of symptoms. The findings suggest potential different but overlapped mechanisms behind the vestibular and auditory symptoms of migraine. Considering the different patterns of migraine-related symptoms may provide deeper insights for patients' prognosis and clinical decision-making.

Clinical and molecular characteristics of Korean patients with Kabuki syndrome.

INTRODUCTION: Kabuki syndrome (KS) is a rare disorder characterized by typical facial features, skeletal anomalies, fetal fingertip pad persistence, postnatal growth retardation, and intellectual disabilities. Heterozygous variants of the KMT2D and KDM6A genes are major genetic causes of KS. This study aimed to report the clinical and genetic characteristics of KS. METHODS: This study included 28 Korean patients (14 boys and 14 girls) with KS through molecular genetic testing, including direct Sanger sequencing, whole-exome sequencing, or whole-genome sequencing. RESULTS: The median age at clinical diagnosis was 18.5 months (IQR 7-58 months), and the median follow-up duration was 80.5 months (IQR 48-112 months). Molecular genetic testing identified different pathogenic variants of the KMT2D (n = 23) and KDM6A (n = 3) genes, including 15 novel variants. Patients showed typical facial features (100%), such as long palpebral fissure and eversion of the lower eyelid; intellectual disability/developmental delay (96%); short stature (79%); and congenital cardiac anomalies (75%). Although 71% experienced failure to thrive in infancy, 54% of patients showed a tendency toward overweight/obesity in early childhood. Patients with KDM6A variants demonstrated severe genotype-phenotype correlation. CONCLUSION: This study enhances the understanding of the clinical and genetic characteristics of KS.

Postural Sway Velocity of Deaf Children with and without Vestibular Dysfunction.

BACKGROUND: Sensory information obtained from the visual, somatosensory, and vestibular systems is responsible for regulating postural control, and if damage occurs in one or more of these sensory systems, postural control may be altered. OBJECTIVE: To evaluate and compare the postural sway velocity between children with normal hearing and with sensorineural hearing loss (SNHL), matched by sex and age group, and to compare the postural sway velocity between children with normal hearing and with SNHL, with and without vestibular dysfunction. METHODS: Cross-sectional study that evaluated 130 children (65 with normal hearing and 65 with SNHL), of both sexes and aged between 7 and 11 years, from public schools of the city of Caruaru, Pernambuco state, Brazil. The postural sway velocity of the center of pressure (COP) was assessed by a force platform, in two directions, anteroposterior (AP) and mediolateral (ML)), in three positions, namely bipedal support with feet together and parallel (parallel feet (PF)), bipedal support with one foot in front of the other (tandem foot (TF)), and single-leg support (one foot (OF)), evaluated with the eyes open and closed. RESULTS: Children with SNHL demonstrated greater postural sway velocity compared to children with normal hearing in all the positions evaluated, with significant differences in the AP direction, with the eyes open (PF: p = 0.001; TF: p = 0.000; OF: p = 0.003) and closed (PF: p = 0.050; TF: p = 0.005). The same occurred in the ML direction, with the eyes open (PF: p = 0.001; TF: p = 0.000; OF: p = 0.001) and closed (PF: p = 0.002; TF: p = 0.000). The same occurred in relation to vestibular function, where the children with SNHL with an associated vestibular dysfunction demonstrated greater postural sway velocity compared to children with normal hearing in all the positions evaluated, demonstrating significant differences in the AP direction, with the eyes open (TF: p = 0.001; OF: p = 0.029) and eyes closed (PF: p = 0.036; TF: p = 0.033). The same occurred in the ML direction, with the eyes open (TF: p = 0.000) and with the eyes closed (PF: p = 0.008; TF: p = 0.009). CONCLUSIONS: Children with SNHL demonstrated greater instability of postural control than children with normal hearing in all the directions assessed. Children with SNHL and an associated vestibular dysfunction demonstrated the greatest instability of postural control in this study.

Human Genetics of Semilunar Valve and Aortic Arch Anomalies.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.