Noonan Syndrome

Researchers are studying children with Noonan syndrome who have inadequate growth during or after treatment with human growth hormone (hGH). The study aims to evaluate the effects of three different doses of vosoritide on growth, specifically looking at annualized growth velocity (AGV) after six months of treatment. The long-term safety and effectiveness of vosoritide at the therapeutic dose will be assessed up to when participants reach their final adult height (FAH). This Phase 2, randomized, multicenter trial compares three dosing regimens of vosoritide, which is given as an injection. Participants receive one of three different doses of this experimental drug, provided as a lyophilized powder for reconstitution. The study includes both a short-term evaluation of growth changes over six months and a longer-term assessment of height and safety measures up to 15 years. During the study, children will have regular height measurements and assessments of growth velocity, body proportions, bone density, and bone age. Researchers will also monitor heart conditions, bone-related events, and quality of life using various questionnaires and physical activity scores. Blood and urine tests will track vosoritide levels and biological markers. Safety and growth will be followed every six to twelve months until participants reach their final adult height, which may take up to 15 years.

RASopathies are genetic conditions that affect children's development, causing physical, cognitive, and behavioral challenges. This research aims to find out if Acceptance and Commitment Therapy (ACT), a technique that helps people accept difficult thoughts and feelings, can help caregivers of children with RASopathies manage parenting stress. The study includes an initial pilot phase followed by a randomized trial to compare immediate versus delayed intervention effects. The study involves an 8-week ACT intervention delivered remotely through a mobile app called MetricWire. Participants watch weekly videos lasting 9 to 17 minutes and engage in coaching sessions via video chat—one 75-minute session in week 1 and shorter 20- to 30-minute sessions in weeks 3 and 6. The trial has two phases: a pilot study where all participants receive the intervention immediately, and a randomized controlled trial where participants either start the intervention right away or after approximately 2 months on a waitlist. Caregivers aged 18 or older who care for a child under 18 with a RASopathy and live with the child at least half the time are eligible. They will complete brief daily surveys five days a week and longer questionnaires before and after the intervention, as well as three months later. These assessments measure parenting stress, mindfulness, self-compassion, and related factors. The study monitors feasibility, acceptability, and changes in stress levels over time using electronic assessments and questionnaires.

Myelodysplastic syndromes (MDS) are chronic blood disorders marked by ineffective blood cell production and normal marrow richness. This research aims to understand the biological and clinical aspects of MDS, including its progression to acute leukemia, which occurs in 30 to 40% of cases. The study focuses on the genetic and molecular diversity of MDS and seeks to identify markers predicting disease progression through a biocollection. The study involves collecting and analyzing biological material from patients diagnosed or suspected of having MDS. It explores three key scientific projects: splicing abnormalities related to SF3B1 mutations, the role of chromosomal deletions such as 5q affecting splicing genes RBM22 and SLU7, and the progression of MDS to acute myeloid leukemia by studying the clonal architecture of malignant cells. These projects use advanced genetic and molecular analysis techniques to deepen understanding of MDS mechanisms. Participants provide biological samples and clinical data, which are used for detailed genetic and functional studies. The study monitors patients over time to observe disease evolution and identify prognostic markers. The primary outcome is an epidemiologic study of the MDS patient cohort over five years. Participation includes consenting to data and sample collection, enabling researchers to analyze molecular changes and better understand MDS progression and prognosis.

RASopathies are a group of genetic conditions caused by changes in genes related to the Ras/MAPK pathway. People with these conditions may experience developmental challenges, cognitive disabilities, poor growth, birth defects, and have a higher risk of certain cancers. Researchers are studying how genes and environmental factors contribute to cancer development and other health issues in people with RASopathies to improve early detection and prevention. Participants include children and adults diagnosed with or suspected to have a RASopathy, as well as their family members. The study involves collecting medical histories, reviewing medical records, and obtaining biological samples such as blood, urine, saliva, and cheek cell samples for genetic testing. Some participants may undergo additional tests like skin biopsies, physical exams by specialists, imaging scans including CT, ultrasound, bone density, MRI, and other functional tests. Consent is obtained for specific procedures as needed. Participation lasts indefinitely, with occasional follow-up visits or contacts by phone or mail. Researchers will monitor participants’ clinical features, cancer development, and other related health manifestations over time. The study also maintains a biospecimen repository for future research and aims to identify new features linked to RASopathy genetic variations. Outcome measures include ongoing clinical, genetic, and environmental evaluations.

This research focuses on Noonan syndrome, a rare genetic disorder affecting multiple body systems including the face, heart, growth, skeleton, and development. The study aims to create a collection of biological samples to better understand the disease's mechanisms and identify factors that predict how the condition progresses over time. Patients with Noonan syndrome or related conditions are followed at Toulouse University Hospital as part of this observational study. During regular medical check-ups, patients will provide extra samples of blood and urine, which will be collected and securely stored for research purposes. These samples will help researchers answer important questions about the disease and support future studies. Participation involves consenting to the collection and use of these biological samples. Participants will be involved during their routine visits, where additional blood and urine samples will be taken. The researchers will maintain confidentiality and use these samples to build a biological collection. The main outcome measure is the establishment of this collection from patients with Noonan syndrome or related disorders. The study runs from January 2022 through January 2032, with no intervention beyond sample collection.

Researchers are evaluating a non-invasive prenatal diagnosis (NIPD) method for single-gene disorders (SGD) using cell-free fetal DNA (cffDNA) found in maternal blood. This approach offers early and accurate diagnosis from 9 weeks of pregnancy without the miscarriage risks linked to invasive procedures. The study aims to broaden the use of this method to any monogenic disorder by leveraging a collaborative French network, improving current diagnosis options which are limited and mostly research-based. The study involves taking blood samples from pregnant women who are undergoing invasive prenatal diagnosis or counselling due to family history of specific single-gene disorders. These disorders involve mutations in genes such as HBB, CFTR, FMR1, SMN1, and others. Blood plasma is collected and stored for analysis to detect fetal genetic mutations using advanced sequencing techniques. The method is targeted, focusing on specific DNA regions related to the family’s disorder, avoiding broader genome sequencing. Participants will provide blood samples during routine prenatal diagnosis visits, and their samples will be analyzed for the presence and concentration of fetal DNA. Researchers will measure how accurately they can classify affected or unaffected fetuses and monitor inconclusive results. Secondary measures include DNA concentration, sequencing quality, and turnaround time for results. The study will follow participants until birth in some cases, comparing prenatal findings with newborn genotypes. Participation duration varies depending on prenatal visits and follow-up care.

This research aims to improve genetic health for underserved children with rare disorders living along the Texas-Mexico border. It focuses on providing easier access to genetic evaluation and testing for Hispanic minority pediatric patients who often lack these services. The study seeks to shorten the time it takes to diagnose rare genetic diseases and enhance healthcare provider knowledge through education and machine learning support. Participants will receive virtual genetics evaluations through a web-based platform called Consultagene, designed to simplify patient pathways and deliver care remotely in the Rio Grande Valley. All 200 recruited children will undergo whole genome sequencing (WGS) to detect genetic variants, including copy number variations and single nucleotide variants, which may aid in medical decision-making. The study also aims to build genomic competency among frontline healthcare providers to speed up referrals. Throughout the study, researchers will monitor how long it takes to reach a diagnosis within 12 months. Participants’ genetic data and diagnostic results will be collected and interpreted to support clinical care. The study involves ongoing education and machine learning tools to improve referrals and outcomes. Participation extends from enrollment through virtual evaluations, genetic testing, and follow-up over the study period ending in January 2027.

Researchers are studying adults with rare and complex genetic syndromes that affect multiple body systems and often include intellectual disability. These patients typically receive specialized care from multiple specialists during childhood, but as medical advances have extended life expectancy, many are now living into adulthood. The study aims to understand the medical needs, comorbidities, medication use, and quality of life impacts for adults with these rare syndromes, addressing a gap in adult care and guidelines. This research involves a retrospective review of medical files, including medical history, laboratory results, additional tests, and records of physical and psychological complaints. There is no active treatment or intervention, as the study collects and analyzes existing data to gain insights about health issues and medication adaptations needed for these syndromes. Participants' medical records will be analyzed to evaluate the presence of physical health problems, laboratory values, physical and psychological complaints, and medication use over a one-year period. The study uses statistical software for analysis and aims to improve understanding of adult care needs for these rare genetic conditions. The study began in October 2018 and will continue through January 2030.

Researchers are conducting a multi-centre observational study focused on children with rare inherited cardiac conditions, particularly those diagnosed with cardiomyopathy before age 16. The study aims to better understand the genetic and environmental factors influencing these heart muscle diseases, including disease progression and response to treatments. By collecting genetic information and clinical data, the study seeks to identify new personalized treatment options for affected children. Participants include children with diagnosed inherited cardiac conditions and their parents. The study collects baseline demographic, imaging, and genotyping data primarily from routine clinical care, including whole genome sequencing. Some participants may provide blood or saliva samples for genetic and biomarker analysis. Family members of deceased patients might also donate stored tissue or samples if available. The study plans to follow participants over a 5-year period. During the study, researchers will access clinical data including health information and results from routine tests like echocardiograms. Some procedures may involve minimal risk, such as blood or saliva collection. The study focuses on monitoring the participants' health outcomes and genetic markers to understand disease progression. The total follow-up duration for each participant is up to five years, with data collected throughout this period.

This research aims to evaluate the effectiveness of trametinib treatment in children and adolescents aged 0 to 18 years who have hypertrophic cardiomyopathy (HCM) caused by genetic mutations in the RAS/MAPK pathway, conditions known as RASopathies, including Noonan syndrome. These genetic mutations lead to severe heart muscle thickening, and while MEK kinase inhibitors like trametinib are used for certain cancers with similar mutations, their impact on HCM in RASopathies requires thorough study. Participants will be randomly assigned to one of two groups for the first three months: one group will receive trametinib along with standard treatment (beta-blockers and disopyramide), and the other group will receive only the standard treatment. After this phase, if trametinib shows greater effectiveness, the control group will also start trametinib for a 12-month period while the initial trametinib group continues its treatment. Trametinib is given orally once daily at a dose of 0.025 mg/kg, and the standard therapy includes oral disopyramide and beta-blockers. During the study, participants will undergo assessments including echocardiography and laboratory tests to monitor heart muscle thickness and enzyme levels over one year. Additional evaluations include measuring MEK kinase activity at six months and cardiac magnetic resonance imaging at one year. These tests will help determine the treatment's impact and safety. The overall study duration includes the initial phase and an extended treatment phase lasting up to 12 months, with ongoing monitoring to assess treatment effects and patient health.