Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes.

Boston Children's Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Children's Rare Disease Collaborative (CRDC), the hospital offers CLIA-grade exome and genome sequencing, along with other sequencing types, to patients enrolled in specialized rare disease research studies. The data, consented for broad research use, are harmonized and analyzed with CRDC-supported variant interpretation tools.

Management of Prenatal Expanded Genetic Carrier Screening Results for Autosomal Recessive Sensorineural Hearing Loss.

Objective: Expanded carrier screening (ECS) identified couples at-risk to have a baby with an autosomal recessive genetic condition. Several genes implicated in sensorineural hearing loss (SNHL) are included in prenatal or preconception genetics ECS testing. Early identification of SNHL risk may enable prognostication of hearing loss, early educational intervention, and minimization of unnecessary diagnostic testing.

Microbial DNA extraction method for avian feces and preen oil from diverse species.

As DNA sequencing technology continues to rapidly improve, studies investigating the microbial communities of host organisms (i.e., microbiota) are becoming not only more popular but also more financially accessible.

Chromosomal structural rearrangements implicate long non-coding RNAs in rare germline disorders.

In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is long non-coding RNAs (lncRNAs), which has recently been implicated in the regulation of diverse molecular processes. However, because lncRNAs do not encode protein, there is uncertainty regarding what constitutes a pathogenic lncRNA variant, and thus annotating such elements is challenging.

Rare germline disorders implicate long non-coding RNAs disrupted by chromosomal structural rearrangements.

In recent years, there has been increased focus on exploring the role the non-protein-coding genome plays in Mendelian disorders. One class of particular interest is long non-coding RNAs (lncRNAs), which has recently been implicated in the regulation of diverse molecular processes. However, because lncRNAs do not encode protein, there is uncertainty regarding what constitutes a pathogenic lncRNA variant, and thus annotating such elements is challenging.

PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss.

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing. PKHD1L1 was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants in PKHD1L1 also cause hearing loss in humans.

, A Gene Involved in the Stereocilia Coat, Causes Autosomal Recessive Nonsyndromic Hearing Loss.

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing. was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants in also cause hearing loss in humans.

Vestibular Preservation in Pediatric Cochlear Implantation.

Objectives: Evaluate the rate of preserved vestibular function in pediatric cochlear implant surgery.

Study Design: Retrospective case review.

Methods: Pre- and post-operative vestibular tests were compared in children who underwent cochlear implantation at a tertiary level pediatric hospital over a 4-year period.

Programming Levels and Speech Perception in Pediatric Cochlear Implant Recipients With Enlarged Vestibular Aqueduct or GJB2 Mutation.

Objective: To determine the relationship between hearing loss etiology, cochlear implant (CI) programming levels, and speech perception performance in a large clinical cohort of pediatric CI recipients.

Study Design: Retrospective chart review.

Setting: Tertiary care hospitals.

Otolaryngologic Manifestations of Trisomy 13 and Trisomy 18 in Pediatric Patients.

Objective: The survival rate of patients with trisomy 13 and trisomy 18 has increased dramatically over the past two decades. We sought to comprehensively describe the otolaryngologic clinical characteristics and procedures required for these patients at our institution.

Methods: We performed algorithmic identification of patients with a diagnosis of trisomy 13 and trisomy 18 for whom the otolaryngology service provided inpatient or outpatient care at our institution between the dates of February 1997 and March 2021.

Models of Classroom Assessment for Course-Based Research Experiences.

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment - 1) Assessing Laboratory Work and Scientific Thinking; 2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; 3) Appraising Forms of Scientific Communication; and 4) Metacognition of Learning - along with a set of practices for each aim.

Congenital Cytomegalovirus Screening in Massachusetts Birth Hospitals: A Statewide Survey.

This study sought to assess the current state of screening for congenital cytomegalovirus infection in newborns among birth hospitals and newborn nurseries in the state of Massachusetts. A survey assessing hospital protocols for cytomegalovirus testing in newborns was distributed to all birth hospitals and newborn nurseries in Massachusetts from November 2020 to February 2021. 73.

Exome Sequencing Expands the Genetic Diagnostic Spectrum for Pediatric Hearing Loss.

Objectives: Genetic testing is the standard-of-care for diagnostic evaluation of bilateral, symmetric, sensorineural hearing loss (HL). We sought to determine the efficacy of a comprehensive genetic testing method, exome sequencing (ES), in a heterogeneous pediatric patient population with bilateral symmetric, bilateral asymmetric, and unilateral HL.

Methods: Trio-based ES was performed for pediatric patients with confirmed HL including those with symmetric, asymmetric, and unilateral HL.

Genetic testing for pediatric hearing loss: no time to waste.

Since the discovery of the first human deafness gene a quarter of a century ago, our approach to clinical evaluation of children with hearing loss has changed dramatically. What was once a low-yield scattershot approach has changed to a clearly definable pathway involving genetic testing, imaging, and congenital cytomegalovirus testing. There still however is a great deal of work to be done to expand the correct use of this testing, particularly genetic testing.

Hearing Stability in Patients With Unilateral Hearing Loss Due to Congenital CMV.

Objective: To determine the incidence and severity of progressive hearing loss in both ears in a population of longitudinally-tracked patients with unilateral hearing loss due to congenital cytomegalovirus (cCMV). By determining the natural history of unilateral hearing loss due to cCMV infection, we aim to facilitate therapeutic recommendations.

Study Design: Retrospective chart review.

Pain at the Cochlear Implant Site Requiring Device Removal in Pediatric Patients.

Objectives: Idiopathic pain at the cochlear implant (CI) site outside of the immediate postoperative period is an uncommon occurrence but may necessitate device explantation. Our objective was to describe the clinical course for pediatric patients with CI site pain who ultimately required device explantation.

Study Design: Retrospective chart review.

Evaluation of copy number variants for genetic hearing loss: a review of current approaches and recent findings.

Structural variation includes a change in copy number, orientation, or location of a part of the genome. Copy number variants (CNVs) are a common cause of genetic hearing loss, comprising nearly 20% of diagnosed cases. While large deletions involving the gene STRC are the most common pathogenic CNVs, a significant proportion of known hearing loss genes also contain pathogenic CNVs.

Peripheral Vestibular Dysfunction Is a Common Occurrence in Children With Non-syndromic and Syndromic Genetic Hearing Loss.

Hearing loss (HL) is the most common sensory deficit in humans and is frequently accompanied by peripheral vestibular loss (PVL). While often overlooked, PVL is an important sensory dysfunction that may impair development of motor milestones in children and can have a significant negative impact on quality of life. In addition, many animal and models of deafness use vestibular hair cells as a proxy to study cochlear hair cells.

Comprehensive medical evaluation of pediatric bilateral sensorineural hearing loss.

Children with bilateral sensorineural hearing loss (SNHL) should undergo a comprehensive medical evaluation to determine the underlying etiology and help guide treatment and counseling. In this article, we review the indications and rationale for medical evaluation of pediatric bilateral SNHL, including history and physical examination, imaging, genetic testing, specialist referrals, cytomegalovirus (CMV) testing, and other laboratory tests. Workup begins with a history and physical examination, which can provide clues to the etiology of SNHL, particularly with syndromic causes.

Hearing Aid Use in Children With Unilateral Hearing Loss: A Randomized Crossover Clinical Trial.

Objectives/hypothesis: In children with mild to moderately severe unilateral hearing loss (UHL), assess whether subject-reported quality of life (QOL) and teacher- and parent-reported perception of listening difficulty are affected by use of a hearing aid (HA) with baseline accommodations, compared to children receiving only baseline accommodations.

Study Design: Randomized crossover clinical trial.

Methods: Thirty-seven children 6-12 years of age with mild to moderately severe UHL and ≥80% word recognition scores in the poorer hearing ear were randomized into arm 1, using baseline accommodations (frequency-modulated system and strategic seating) for 12 weeks, followed by addition of a HA for 12 weeks.

Neuroimaging in Kabuki syndrome and another KMT2D-related disorder.

Recognition of distinct phenotypic features is an important component of genetic diagnosis. Although CHARGE syndrome, Kabuki syndrome, and a recently delineated KMT2D Ex 38/39 allelic disorder exhibit significant overlap, differences on neuroimaging may help distinguish these conditions and guide genetic testing and variant interpretation. We present an infant clinically diagnosed with CHARGE syndrome but subsequently found to have a de novo missense variant in exon 38 of KMT2D, the gene implicated in both Kabuki syndrome and a distinct KMT2D allelic disorder.