Commentary: “Investigating the use of a patient-facing digital app to support Lynch Syndrome carriers in the management of their condition”
Madonna Jonhera*, Megan Hopkinson, Stan Shepherd
University of Leicester, University of Birmingham, Instant Access Medical, UK
Introduction
Lynch syndrome (LS) is an autosomal dominant inherited cancer predisposition syndrome, and the most common cause of inherited colorectal cancers1. We conducted a study surveying LS carriers to identify the challenges they face in managing their condition. Based on these insights, we co-developed an app to support LS carriers in staying up-to-date with their management and evaluated if digital solutions could improve care2. In this commentary, we explain the rationale behind the app, describe the process of co-development, highlight key findings from the app’s analytics, and outline future directions for the app.
Background
Although historically considered a rare disease, researchers estimate that LS affects 1 in 400 people, and only 5% of carriers are diagnosed and aware that they have the condition3.
It requires lifelong surveillance as the risk of cancers including colorectal, endometrial, prostate, and ovarian cancer can be higher than the general population by an average of 56%, 48%, 24%, and 13%, respectively. The UK Cancer Genetics Group (UKCGG) has published management guidelines that recommend, 2-yearly bowel colonoscopy screening, Helicobacter pylori (H. pylori) testing, gynaecological reviews for women, aspirin chemoprevention, genetic testing for at-risk family members, and healthy lifestyle advice4.
The Lord Darzi investigation highlighted that the current NHS App had fallen short of its potential and emphasised the need for technological advancements that would create a “predict and prevent” model for healthcare in England5. There is an increased disease burden of long-term conditions and an expectation for general practitioners (GPs) to oversee management6. However, the current GP shortage, along with the closing of GP practices in areas of higher deprivation, means that the NHS, at present, is not adequately equipped to meet these needs, and the burden of condition management can often fall upon LS carriers5,6.
Digital solutions, like patient-facing self-management apps, may encourage patients to keep up-to-date with their management, and have been successful in other disease areas7. For example, a smartphone app for diabetes type II was shown to improve medication adherence amongst and medication non-adherent Asian population, with >80% stating the app made them more adherent7. Furthermore, a self-management score has been produced to assess self-management behaviour in diabetes patients, which has become a widely used tool by patients and healthcare professionals (HCPs) to help manage their condition and improve communication between HCPs and patients8. A mobile app specifically for LS management had not previously been launched in the UK.
95% of UK adults own smartphones, and their mobility means that health apps may be used in any location, at any time, and makes access to healthcare very convenient for a large proportion of society9. Additionally, digital healthcare has the potential to minimize ethnic and racial disparities in access to healthcare, when black and ethnic minorities are prioritised for inclusion in design processes10. However, digital illiteracy and a lack of trust in IT remain challenges for the uptake of healthcare apps in the wider population, particularly in older individuals11. The combined use of healthcare professional visits alongside health apps, as well as access to digital champions who can help and empower individuals using technology have proven to be successful in improving adoption of digital technology12,13.
DOI: 10.29245/2572-9411/2025/1.1221 View / Download PdfUnraveling Novel Pathogenic CAPN3 Variants in Limb-Girdle Muscular Dystrophy R1
Sukanya Banerjee and Bishan Dass Radotra*
Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh-160012, India
Limb-Girdle Muscular Dystrophy R1 (LGMDR1) is an autosomal recessive neuromuscular disorder caused by mutations in the calpain-3 (CAPN3) gene, which encodes a calcium-dependent intracellular protease. Various pathogenic mutations have been reported to date, typically leading to weakness of the pelvic and shoulder girdle muscles. However, the clinical and pathological features of LGMDR1 are often heterogeneous and overlap with those of other LGMD subtypes, making a definitive molecular diagnosis essential for understanding the disease pathogenesis. Immunoblot analysis of calpain-3 protein revealed either complete or partial loss of expression in patients with LGMD. Additionally, multiple CAPN3 variants were identified and evaluated using in silico pathogenicity prediction tools. Alongside previously known mutations, Sanger sequencing also revealed novel pathogenic variants in the CAPN3 gene. Identification of genetic variants in LGMDR1 patients helps explore the mechanisms of disease pathogenesis and may support more accurate diagnosis and prognostication.
DOI: 10.29245/2572-9411/2025/1.1218a View / Download PdfCommentary: Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington’s disease
Rocio Gomez-Pastor.
Department of Neuroscience, University of Minnesota, School of Medicine, Minneapolis, MN, United States.
Huntington’s disease (HD) is a rare, inherited neurodegenerative disorder marked by progressive motor impairment, cognitive decline, and psychiatric disturbances. Increasing evidence implicates dysregulated cellular stress responses in HD pathogenesis, particularly involving the antagonistic interplay between the transcription factors p53 and heat shock factor 1 (HSF1)—key regulators of both cancer biology and neurodegeneration. This commentary highlights recent findings by Mansky et al., which uncover a novel mechanism whereby mutant huntingtin (mtHTT) stabilizes p53, triggering the degradation of HSF1 in striatal neurons. This mechanistic link offers new insight into how disrupted proteostasis drives neuronal vulnerability in HD, highlighting the p53–HSF1 axis as a promising therapeutic target. Additionally, we examine evidence that similar regulatory dynamics may contribute to other neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, suggesting a potentially conserved molecular pathway underlying neuronal degeneration in rare disorders. These findings underscore the therapeutic potential of modulating stress-responsive transcriptional networks to slow or prevent disease progression in HD and related conditions.
DOI: 10.29245/2572-9411/2025/1.1219 View / Download PdfVascular Ehlers-Danlos Syndrome: Current Understanding and Treatment Strategies
Reece M. Foehr1, Erik D. Foehr2*
1Saint Louis University, School of Medicine, Saint Louis, MO, USA
2Kin Therapeutics, Novato, CA, USA
Vascular Ehlers-Danlos Syndrome (vEDS) is a rare and severe subtype of Ehlers-Danlos Syndrome (EDS), a group of inherited disorders affecting connective tissue. Unlike other EDS subtypes primarily characterized by joint hypermobility and skin elasticity, vEDS is distinguished by its impact on the vascular system, posing a significant risk of life-threatening complications1. This review aims to provide a concise overview of vEDS, encompassing its genetic basis, clinical manifestations, diagnostic approaches, and current treatment strategies.
DOI: 10.29245/2572-9411/2025/1.1217 View / Download Pdf