Novel Intragenic and Genomic Variants Highlight the Phenotypic Variability in -Related Disease.

: Disruption of results in microphthalmia with linear skin lesions (MLS) characterized by microphthalmia/anophthalmia, corneal opacity, aplastic skin lesions, variable central nervous system and cardiac anomalies, intellectual disability, and poor growth in heterozygous females. Structural variants consisting of chromosomal rearrangements or deletions are the most common variant type, but a small number of intragenic variants have been reported. : Exome sequencing identified variants affecting .

KIF11 Variants Associated With Novel Renal System Involvement-Two Cases That Expand the Phenotypic Spectrum of Microcephaly With or Without Chorioretinopathy, Lymphedema, or Impaired Intellectual Development.

Pathogenic variants in KIF11 are linked to microcephaly with or without chorioretinopathy, lymphedema, or impaired intellectual development (MCLMR). To our knowledge, renal phenotypes have not been described in the literature in association with KIF11-related disorders. This study is a case report of two probands with heterozygous pathogenic variants in KIF11 who presented with the common clinical features of MCLMR but also had additional renal involvement not previously reported as associated phenotypes of MCLMR, elucidating phenotypic expansion of this syndrome.

Single center experience developing sustainable genetics clinical care: a model to address workforce challenges in medical genetics.

Purpose Of Review: The national workforce shortage in genetics is being evaluated in order to identify a sustainable solution to the increasing demand for genomic services. An innovative solution to the short term needs is to integrate advanced practice providers (APPs) and embed genetic counselors into both outpatient and inpatient specialty care. Incorporating APPs into a genetic service is not unique in itself, but the method of implementation at Medical College of Wisconsin (MCW) was, at the time, unchartered.

Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 - implications for post COVID-19 conditions.

Background: Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC).

Methods: The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls.

Lower extremity inter-joint coupling angles and variability during gait in pediatric hypermobility spectrum disorder.

Complex musculoskeletal complications in children with hypermobility spectrum disorder (HSD) include pain, proprioception deficits, and joint instability, which may result in movement dysfunction during walking. However, no studies have explored the inter-joint coordination deficits in children with HSD. The purpose of this study was to determine the lower extremity inter-joint coupling angles, patterns, and variability during walking in children with HSD compared to children without HSD (non-HSD).

A novel termination site in a case of Stüve-Wiedemann syndrome: case report and review of literature.

Stüve-Wiedemann syndrome (SWS) is a rare autosomal recessive disorder that is characterized by bowing of long bones, dysautonomia, temperature dysregulation, swallowing and feeding difficulties, and frequent respiratory infections. Respiratory distress and hyperthermic events are the leading causes of early neonatal death, and most patients are not expected to survive past infancy. Here, we report on the survival of a 5-year-old male with SWS, discussing his case presentation, providing a brief clinical course, and discussing the outcome.

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.

Background: Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.

Methods: In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries.

Changes in Symptom Severity among Children and Adolescents with Obsessive-Compulsive Disorder during the COVID-19 Pandemic: A 2-year Follow-up.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused significant global turmoil, including changes in social and societal conduct such as lockdowns, social isolation, and extensive regulations. These changes can be major sources of stress. The first wave of the pandemic (April-May 2020) was a time of global uncertainty.

The association of pain with gait spatiotemporal parameters in children with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder.

Background: Children with hypermobility spectrum disorder/hypermobile Ehlers-Danlos syndrome (HSD/hEDS) have a high prevalence of chronic pain, which may influence gait dynamics. However, little is known about pain outcomes and their association with gait spatiotemporal parameters in children with HSD/hEDS.

Research Question: Does pain correlate with gait spatiotemporal parameters in children with HSD/hEDS?

Methods: Eighteen children with HSD/hEDS and eighteen typically developing (TD) children participated in the study.

Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt.

Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease.

Methylation signatures as biomarkers for non-invasive early detection of breast cancer: A systematic review of the literature.

Background: Early detection of breast cancer would help alleviate the burden of treatment for early-stage breast cancer and help patient prognosis. There is currently no established gene panel that utilizes the potential of DNA methylation as a molecular signature for the early detection of breast cancer. This systematic review aims to identify the optimal methylation biomarkers for a non-invasive liquid biopsy assay and the gaps in knowledge regarding biomarkers for early detection of breast cancer.

Clinical course and therapeutic trial for a case of congenital secretory diarrhea due to novel GUCY2C variant.

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate-cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate-cyclase 2C (GC-C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels.

Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Vosoritide is a recombinant C-type natriuretic peptide analogue that increases annualised growth velocity in children with achondroplasia aged 5-18 years. We aimed to assess the safety and efficacy of vosoritide in infants and children younger than 5 years.

Methods: This double-blind, randomised, placebo-controlled, phase 2 trial was done in 16 hospitals across Australia, Japan, the UK, and the USA.

Attaining Diagnostic Excellence: How the Structure and Function of a Rare Disease Service Contribute to Ending the Diagnostic Odyssey.

Patients with rare or otherwise undiagnosed disorders frequently find themselves on a diagnostic odyssey, the often-prolonged journey toward diagnosis that can be characterized by significant physical, emotional, and financial hardship, as well as by diagnostic errors and delays. The wider availability of clinical exome sequencing has helped end many diagnostic odysseys, though diagnostic success rates of around 35% for exome sequencing leave many patients undiagnosed. Diagnostic yields can be improved via the implementation of advanced genetic testing modalities, though both these modalities and exome sequencing perform significantly better when paired with high-quality phenotypic data.

More Than Results: The Clinical and Research Relationship in the Evolving Detection and Surveillance of SARS-CoV-2.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, real-time reverse transcription polymerase chain reaction (RT-PCR) became an essential tool for laboratories to provide high-sensitivity qualitative diagnostic testing for patients and real-time data to public health officials. Here we explore the predictive value of quantitative data from RT-PCR cycle threshold (Ct) values in epidemiological measures, symptom presentation, and variant transition.

Methods: To examine the association with hospitalizations and deaths, data from 74,479 patients referred to the Avera Institute for Human Genetics (AIHG) for COVID-19 testing in 2020 were matched by calendar week to epidemiological data reported by the South Dakota Department of Health.

What the pediatric endocrinologist needs to know about skeletal dysplasia, a primer.

Children with skeletal dysplasia are frequently referred to pediatric endocrinologists due to short stature. These children may present with disproportionate growth or medical histories that point to a skeletal dysplasia. This primer will discuss when to be concerned about skeletal dysplasia, the initial steps in evaluation for a skeletal dysplasia, and new therapies that are either recently approved or in development.

Increased attention allocation to stimuli reflecting end-states of compulsive behaviors among obsessive compulsive individuals.

Attentional research in OCD has focused solely on threat stimuli, assumed to provoke related obsessions and ensuing compulsions. OCD-related stimuli depicting the completion of compulsive acts ("end-states") have yet to be examined. Past research also neglected to explore the reliability of tasks used.

Pain Characteristics and Symptom Management in Children with Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder.

Aims: This study aims to investigate pediatric hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) pain features and management strategies.

Methods: This is a mixed-methods, cross-sectional study design using patient-reported outcomes in 21 children diagnosed with hEDS/HSD. Children who reported bothersome pain were interviewed for pain features.

Attention allocation in OCD: A systematic review and meta-analysis of eye-tracking-based research.

Introduction: Cognitive models of obsessive-compulsive disorder (OCD) implicate heightened attention allocation to stimuli related to one's obsessions in the disorder. Recently, to overcome several limitations of reaction time-based measures, eye-tracking methodology has been increasingly used in attentional research.

Methods: A meta-analysis of studies examining attention allocation towards OCD-related vs.

Reward functioning from an attentional perspective and obsessive-compulsive symptoms-an eye-tracking study.

Background: Recently, a novel approach to obsessive-compulsive disorder has emerged, implicating altered reward functioning in the disorder. Yet, no study to date has directly examined the attentional aspect of reward functioning in participants with obsessive-compulsive (OC) symptoms, with past research mostly relying on reaction-time-based tasks.

Methods: A reward-based value-modulated attentional capture task was completed by a sample of nonclinical student participants-44 with high (HOC) and 48 with low (LOC) levels of OC symptoms.