Split Hand-Foot and Deafness in a Patient with 7q21.13-q21.3 Deletion Not Including the DLX5/6 Genes.

Split Hand-Foot Malformation (SHFM) is a congenital limb defect characterized by a median cleft of the hands and/or feet due to the absence/hypoplasia of the central rays. It may occur as part of a syndromic condition or as an isolated malformation. The most common of the six genetic loci identified for this condition is correlated to SHFM1 and maps in the 7q21q22 region. SHFM1 is characterized by autosomal dominant transmission, incomplete penetrance and variable expressivity. Associated features often include hearing loss, intellectual disability/developmental delay and craniofacial abnormalities. Disruption of the DLX5/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype. Through SNP array, we analyzed a patient affected by SHFM1 associated with deafness and an abnormality of the inner ear (incomplete partition type I); we identified a deletion in 7q21, not involving the DLX5/6 genes, but including exons 15 and 17 of DYNC1I1, known to act as exonic enhancers (eExons) of the DLX5/6 genes. We further demonstrated the role of DYNC1I1 eExons in regulating DLX5/6 expression by means of showing a reduced expression of the DLX5/6 genes through RT-PCR in a patient-derived lymphoblastoid cell line. Furthermore, our data and a review of published cases do not support the hypothesis that DLX5/6 are imprinted in humans. This work is an example of how the disruption of regulatory elements can be responsible for congenital malformations.

Monitoring of Auditory Function in Newborns of Women Infected by SARS-CoV-2 during Pregnancy.

BACKGROUND: Gestational SARS-CoV-2 infection can impact maternal and neonatal health. The virus has also been reported to cause newborn sensorineural hearing loss, but its consequences for the auditory system are not fully understood. OBJECTIVE: The aim of this study was to evaluate the impact of maternal SARS-CoV-2 infection during pregnancy on newborn' hearing function during the first year of life. METHODS: An observational study was conducted from 1 November 2020 to 30 November 2021 at University Modena Hospital. All newborns whose mother had been infected by SARS-CoV-2 during pregnancy were enrolled and underwent audiological evaluation at birth and at 1 year of age. RESULTS: A total of 119 neonates were born from mothers infected by SARS-CoV-2 during pregnancy. At birth, five newborns (4.2%) presented an increased threshold of ABR (Auditory Brainstem Evoked Response), but the results were confirmed only in 1.6% of cases, when repeated 1 month later, while the ABR thresholds in all other children returned to normal limits. At the 1-year follow-up, no cases of moderate or severe hearing loss were observed, while concomitant disorders of the middle ear were frequently observed. CONCLUSIONS: Maternal SARS-CoV-2 infection, regardless of the trimester in which it was contracted, appears not to induce moderate or severe hearing loss in infants. It is important to clarify the possible effect of the virus on late-onset hearing loss and future research is needed.

Genetic and Non Genetic Hearing Loss and Associated Disabilities: An Epidemiological Survey in Emilia-Romagna Region.

Hearing loss is one of the most common congenital sensory disorders. It can be associated with several comorbidities, in particular developmental disabilities (DD). In Emilia-Romagna (ER), a region in Northern Italy, Child and Adolescent Mental Health Services (CAMHS) provide the diagnostic framework and treatment for these conditions. The aim of the present study is to evaluate the prevalence of hearing loss, both isolated or in association with comorbidities, in the juvenile population. The study draws its data from the ER Childhood and Adolescent Neuropsychiatry Information System (SINPIAER), an Administrative Healthcare Database collecting the clinical data of all those who have attended CAMHS since 2010. The most frequent type of hearing loss was bilateral sensorineural hearing loss, which was present in 69-72% of the cases, while bilateral conductive hearing loss was the second most common type, ranging from 8 to 10%. Among DD, congenital malformations, mental retardation, visual impairment, and cerebral palsy were the most common. In particular, autism spectrum disorders show increasing incidence and prevalence among CAMHS users in ER region. In-depth knowledge of hearing loss epidemiology and related conditions, such as developmental disabilities, in the juvenile population is crucial for disease prevention, health planning, and resource allocation.

Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes.

Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n = 11) and Hennekam syndrome (HS) (n= 40). Both conditions are characterized by a typical facial gestalt and mild to moderate intellectual disability, but differ in the occurrence of neonatal hypotonia and feeding problems, hearing loss, tracheal anomalies, and osteopenia in VMS, and lymphedema in HS. VMS can be caused by autosomal recessive variants in DCHS1 as well, and HS can also be caused by autosomal recessive variants in CCBE1 and ADAMTS3. Here we report two siblings with VMS and one girl with HS, all with FAT4 variants, and provide an overview of the clinical findings in all patients reported with FAT4 variants. Our comparison of the complete phenotypes of patients with VMS and HS indicates a resemblance of several signs, but differences in several other main signs and symptoms, each of marked importance for affected individuals.

Sequential pediatric bilateral cochlear implantation: The effect of time interval between implants.

OBJECTIVE: To examine speech intelligibility in children subjected to sequential bilateral cochlear implants (CI) surgery and to assess the influence of the inter-stage interval duration. INTRODUCTION: Binaural hearing recovery can have additional benefits, especially in speech and language development in patients with congenital profound sensorineural hearing loss; so recently there has been an increase in the number of children receiving bilateral CI. METHODS: Twenty-seven children who underwent sequential bilateral cochlear implant (SBCI) with a short (1-3 yrs), medium (4-6 yrs) and long (7-12 yrs) range interval between both implantations, respectively, were evaluated. All patients underwent periodic speech perception test in quiet and noise after second implant activation in three conditions: with the first or second implant alone and with both implants. Results were examined according to the inter-stage interval. RESULTS: Speech intelligibility in noise was significantly better under bilateral conditions than either ear alone, in all three groups. Small improvements were seen in quiet, especially in the third group (6-12 yrs). CONCLUSION: Benefits of second implant in the early-implanted children and after a short inter-implant delay are more evident. However our study support that, even after a long period of deafness and despite a prolonged inter-stage interval, sequential bilateral cochlear implantation should be considered. LEVEL OF EVIDENCE: Level 4.

Cerebrospinal Fluid Leak in Cochlear Implantation: Enlarged Cochlear versus Enlarged Vestibular Aqueduct (Common Cavity Excluded).

Objective. To share our experience of cerebrospinal fluid gusher in cochlear implantation in patients with enlarged cochlear or vestibular aqueduct. Study Design. Case series with comparison and a review of the literature. Methods. A retrospective study was performed. Demographic and radiological results of patients with enlarged cochlear aqueduct or enlarged vestibular aqueduct in 278 consecutive cochlear implant recipients, including children and adults, were evaluated between January 2000 and December 2015. Results. Six patients with enlarged cochlear aqueduct and eight patients with enlarged vestibular aqueduct were identified. Cerebrospinal fluid gusher occurs in five subjects with enlarged cochlear aqueduct and in only one case of enlarged vestibular aqueduct. Conclusion. Based on these findings, enlarged cochlear aqueduct may be the best risk predictor of cerebrospinal fluid gusher at cochleostomy during cochlear implant surgery despite enlarged vestibular aqueduct.

Original Solution for Middle Ear Implant and Anesthetic/Surgical Management in a Child with Severe Craniofacial Dysmorphism.

We describe the novel solution adopted in positioning middle ear implant in a child with bilateral congenital aural atresia and craniofacial dysmorphism that have posed a significant challenge for the safe and correct management of deafness. A five-year-old child, affected by a rare congenital disease (Van Maldergem Syndrome), suffered from conductive hearing loss. Conventional skin-drive bone-conduction device, attached with a steel spring headband, has been applied but auditory restoration was not optimal. The decision made was to position Vibrant Soundbridge, a middle ear implant, with an original surgical application due to hypoplasia of the tympanic cavity. Intubation procedure was complicated due to child craniofacial deformities. Postoperative hearing rehabilitation involved a multidisciplinary team, showing improved social skills and language development.

[Treatment of sudden sensorineural hearing loss (SSHL) with HELP-apheresis: our experience]. / Trattamento dell'Ipoacusia Acuta Neurosensoriale (SSHL) con help-aferesi: nostra esperienza.

In a specific group of patients affected by sudden sensorineural hearing loss (SSHL) with high plasma levels of LDL-cholesterol and/or fibrinogen, HELP-apheresis treatment makes a difference in hearing recovery and is a further option available in SSHL therapy.