Clinical Research Directory

Constitution of a Biological Collection to Study the Pathophysiology in Noonan Syndrome

The present study will establish a collection of biological samples from Noonan patients to be used for research purposes only, with due respect for confidentiality.

National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype

RASopathies, including Noonan syndrome, involve dysmorphisms, metabolic alterations, and an unfavorable lipid profile. This study investigates lipid and glucose metabolism to improve patient care.

Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies

Background: RASopathies are a group of conditions caused by a genetic change. People with a RASopathy may have developmental issues, cognitive disability, poor growth, and birth defects. They may also have an increased risk for developing cancer. Researchers want to learn more. Objective: To learn more about RASopathies, how genes and environmental factors contribute to cancer development in people with RASopathies, and the best way to find these cancers and other conditions early or prevent them. Eligibility: People of any age who have or may have a RASopathy, and their family members. Design: Participants will complete questionnaires about their personal and family medical history. Their medical records will be reviewed. Participants will give blood and urine samples. They will give a saliva or cheek cell sample. Some samples will be used for genetic testing. Participants may have a skin biopsy. Participants may have a physical exam by the RASopathies study team. They may also have exams by additional specialists, such as dentists; urologists; ear, nose, and throat doctors; and neurologists. Participants may have computed tomography of the face and mouth. They may have an ultrasound of the abdomen. They may have a bone density scan. They may have skeletal and/or spine x-rays. They may have magnetic resonance imaging of the brain, low back, chest, and/or heart. They may be photographed. Participants may have other tests, such as sleep, brain and heart electrical activity, speech and swallow, metabolism, hearing, eye, and colon function tests. Participants may sign separate consent forms for some tests. Participation will last indefinitely. Participants may be contacted once in a while by phone or mail. They may have follow-up visits.

A Basket Study of Vosoritide in Children With Turner Syndrome, Short Stature Homeobox-Containing Gene Deficiency, and Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment

The purpose of this basket study in children with Turner syndrome, SHOX deficiency, and Noonan syndrome is to evaluate the effect of 3 doses of vosoritide on growth as measured by AGV after 6 months of treatment. The long-term efficacy and safety of vosoritide at the therapeutic dose will be evaluated up to FAH.

Acceptance and Commitment Therapy for Caregivers of Children With a RASopathy: An Internal Pilot Feasibility Study and Follow-up Randomized Controlled Trial

Background: RASopathies are a group of genetic diseases that affect a child s development. They cause physical, cognitive, and behavioral symptoms. Caring for a child with a RASopathy can be stressful. Acceptance and Commitment Therapy (ACT) is a therapy that helps people become more aware and accepting of difficult thoughts and feelings. ACT has been found to be helpful for parents with high parenting stress. Objective: To find out if Acceptance and Commitment Therapy (ACT) can help caregivers of children with a RASopathy better cope with parenting stress. Eligibility: People aged 18 years or older who care for a child (younger than 18 years) with a RASopathy. The child must live with the caregiver at least 50% of the time. Design: The study is fully remote. Participants need a mobile device that can play audio and video and connect to the internet. They can borrow an iPod if needed. Participants will download a free app called MetricWire. They will use this app to watch videos and answer questions. The first 8 participants will be in a pilot study. They will receive the ACT intervention starting the first week after they begin the study. After the pilot study, we will start a new phase called the randomized trial. In this phase, participants will have a 50-50 chance of being in the group that will start the intervention right away or the group that will start the intervention after about 2 months. Participants will fill out surveys on 5 random days each week. These surveys have 7 questions and take about 2 minutes. They will also fill out 3 longer questionnaires: once before ACT begins, once just after the 8-week study period, and once about 3 months later. Questions will cover topics including: Parenting stress Life satisfaction Self-compassion Uncomfortable feelings and thoughts Mindfulness Participants will take part in an 8-week ACT intervention. They will have one 75-minute session with an ACT coach in the first week. Participants will watch 9- to 17-minute videos each week. The videos talk about how to practice ACT techniques to cope with parenting stress. Participants will have 20- to 30-minute coaching sessions in weeks 3 and 6. The coach will help them practice exercises and work through any problems.

Palliative Care Needs of Children With Rare Diseases and Their Families

The palliative care needs of family caregivers of children with rare diseases and their children are largely unmet, including the need for support to prepare for future medical decision making. This trial will test the FACE-Rare intervention to see if investigators can identify and meet those needs; and if FACE-Rare effects family caregivers' quality of life and child healthcare utilization. Finally, investigators will determine if the intersectionality of child-sex, family-race, Federal poverty level, and social connection influences family quality of life and child health care utilization longitudinally.

Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques

What is this study about? This research is focused on improving the care for people with rare heart muscle diseases, known as rare cardiomyopathies. These are uncommon conditions where the heart muscle becomes stiff, thick, or enlarged, making it harder for the heart to pump blood. Because they are rare, they can be difficult to diagnose and manage. The investigators are testing new, advanced ways of using a heart scan called a Cardiac Magnetic Resonance (CMR). Participants can think of a CMR as a very powerful camera that takes detailed pictures of their heart without using radiation. What is the study trying to learn? Better Diagnosis: The investigators want to see if these new scanning techniques can help us identify these rare heart conditions more clearly and accurately. This means patients could get a correct diagnosis sooner. Personalized Risk Assessment: The investigators want to see if the scan can help us understand the future risk for each patient better. For example, can it help predict which patients are more likely to have a heart rhythm problem or need specific treatments? This helps doctors create a care plan that is tailored just for participants. What does this mean for participants? If participants choose to take part, they will undergo a CMR scan that uses these new techniques. By participating, they will be helping us find better ways to diagnose and care for people with their condition in the future. The goal is to turn uncertainty into clearer, more personalized information for patients and families.

RASopathy Biorepository

The RASopathies are a group of developmental disorders caused by genetic changes in the genes that compose the Ras/mitogen activated protein kinase (MAPK) pathway. New RASopathies are being diagnosed frequently. This pathway is essential in the regulation of the cell cycle and the determination of cell function. Thus, appropriate function of this pathway is critical to normal development. Each syndrome in this group of disorders has unique phenotypic features, but there are many overlapping features including facial features, heart defects, cutaneous abnormalities, cognitive delays, and a predisposition to malignancies. This research study proposes to collect and store human bio-specimens from patients with suspected or diagnosed RASopathies. Once obtained, blood and/or tissue samples will be processed for: metabolic function studies, biomarkers, genetic studies, and/or the establishment of immortalized cell lines. In addition, data from the medical record (including neuropsychological evaluations) and surveys will be stored to create a longitudinal database for research conducted at CCHMC or at other research institutions.

Link Between Abnormal Bleeding and Coagulation Disorders in Noonan Syndromes

Noonan syndrome is a relatively rare genetic disorder, affecting around 1 in every 1,000 to 2,500 children born. Patients often have a tendency to bleed more easily, particularly from the skin or mucocutaneous tissue (such as mouth or nose). Around half of all the patients are affected by bleedings. The causes of bleeding are variable : some are linked to platelet disorders, others to more complex coagulation problems. However, it is difficult to predict exactly which patients are at risk of severe bleeding, for example during surgery. This is why there are as yet no clear recommendations for preventing this risk before medical intervention. However, it is recommended that patients with Noonan syndrome consult a specialist to assess this risk. Unfortunately, the tests carried out are often unreliable in predicting this significant risk of bleeding. In this study, data from a large group of patients with Noonan syndrome, followed-up in different centers in France, will be studied. During a medical meeting as part of their regular follow-up, a medical doctor assessed their tendency to bleed using a standardized questionnaire (standardized ISTH-BAT score). These results will be compared with the biological tests also performed during their medical follow-up. The aim is to better understand whether these tests are useful in predicting the risk of bleeding. Ultimately, this could help practicians to better anticipate surgical or medical interventions in these patients, and limit bleeding-related risk.

A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9

The purpose of this study is to find out if somapacitan is safe and how well somapacitan works in children either born small for gestational age or with Turner syndrome, Noonan syndrome or idiopathic short stature. Somapacitan is a new growth hormone medicine for treatment of low level of growth hormone. The study will last for about 3 years. During the study, the participants will be treated with somapacitan once a week. Somapacitan can be injected anytime during the day. The study doctor or nurse will show how to inject somapacitan, so that the participant knows how to do it at home.

French Registry of Children Treated With Norditropin® for Short Stature Associated With Noonan Syndrome

This is a non-interventional registry of children treated with Norditropin® for short stature due to Noonan Syndrome (NS). This study aims to provide data on long-term growth evolution and safety of Norditropin® as well as Health Related Quality of Life (HRQoL) data. This registry will include the entirety of children treated with Norditropin® for short stature due to NS over the inclusion period. The decision to initiate treatment with commercially available Norditropin® is made by the patient/parents/Legally Acceptable Representative (LAR) and the treating physician before and independently from the decision to include the patient in this study.

MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies

The goal of this study is to evaluate the effectiveness of trametinib treatment in patients with Hyperthropic cardiomyopathy and a genetic mutation in the RAS/MAPK pathway.

Solid Tumors in RASopathies

RASopathies are a group of syndromes, caused by variants of genes involved in the regulation of the Ras/MAP/ERK pathway. This intracellular transduction pathway profoundly affects embryogenic development, organogenesis, synaptic plasticity and neuronal growth. RASopathies are characterized by multi-organ involvement, growth delay, premature aging and haemato-oncological manifestations. Based on evidences provided by literature, cancer screening protocols are applied in some individuals affected by RASopathies, even though detailed information about prevalence and molecular pathogenesis of such tumors is still not clearly elucidate.

Effect of RAS/MAPK Pathway Hyperactivation on Growth' and Bone' Profile of the RASopathies

Costello syndrome (CS) and cardio-facio cutaneous syndrome (CFCS) belongs to RASopathies, a group of multisystemic disorders caused by unregulated signalling through the RAS/MAPK pathway, an intracellular signalling pathway regulating multiple processes such as cellular proliferation, differentiation, survival, apoptosis and also contributing to oncogenesis. They share a recognizable facial appearance, aged appearance, growth delay, muscle-skeletal anomalies, heart defects, neuropsychological features, skin and ocular abnormalities, and cancer predisposition. Even though life expectancy of individuals with CS and CFCS has increased in the last years due to the improvement of patients' care and a more effective prevention of comorbidities, some of the most challenging aspects impacting on everyday living such as growth failure, accelerate senescence and skeletal-muscle defects, still need to be fully understood. This statement underlies the need to improve clinical research protocols with more innovative techniques (multi-omics profiling) in order to better understand the effect of RAS/MAPK pathway hyperactivations on different systems and to define possible personalized treatments.

GROWing Up With Rare GENEtic Syndromes

Introduction Rare complex syndromes Patients with complex genetic syndromes, by definition, have combined medical problems affecting multiple organ systems, and intellectual disability is often part of the syndrome. During childhood, patients with rare genetic syndromes receive multidisciplinary and specialized medical care; they usually receive medical care from 3-4 medical specialists. Increased life expectancy Although many genetic syndromes used to cause premature death, improvement of medical care has improved life expectancy. More and more patients are now reaching adult age, and the complexity of the syndrome persists into adulthood. However, until recently, multidisciplinary care was not available for adults with rare genetic syndromes. Ideally, active and well-coordinated health management is provided to prevent, detect, and treat comorbidities that are part of the syndrome. However, after transition from pediatric to adult medical care, patients and their parents often report fragmented poor quality care instead of adequate and integrated health management. Therefore, pediatricians express the urgent need for adequate, multidisciplinary adult follow up of their pediatric patients with rare genetic syndromes. Medical guidelines for adults not exist and the literature on health problems in these adults is scarce. Although there is a clear explanation for the absence of adult guidelines (i.e. the fact that in the past patients with rare genetic syndromes often died before reaching adult age), there is an urgent need for an overview of medical issues at adult age, for 'best practice' and, if possible, for medical guidelines. The aim of this study is to get an overview of medical needs of adults with rare genetic syndromes, including: 1. comorbidities 2. medical and their impact on quality of life 3. medication use 4. the need for adaption of medication dose according to each syndrome Methods and Results This is a retrospective file study. Analysis will be performed using SPSS version 23 and R version 3.6.0.