Costello Syndrome

RASopathies are genetic conditions that affect childrens 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 chatone 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.

RASopathies are a group of genetic disorders caused by changes in genes that affect the RasMAPK pathway. People with RASopathies may experience developmental problems, cognitive disabilities, poor growth, birth defects, and an increased risk of certain cancers. Researchers aim to learn more about how genes and environmental factors contribute to cancer development and other health issues in individuals with these disorders. Participants include people of all ages who have or may have a RASopathy, as well as their family members. The study is observational and involves collecting detailed personal and family medical histories through questionnaires and reviewing medical records. Participants may provide blood, urine, saliva, or cheek cell samples for genetic testing, and some may have additional tests such as skin biopsies, physical exams, imaging scans, and specialist evaluations. Participation will last indefinitely, with occasional contact by phone or mail and possible follow-up visits. Researchers will monitor various health aspects, including cancer development and other RASopathy-related conditions, using standardized evaluations, biospecimen repositories, and assessments of new clinical features. The study aims to improve understanding of RASopathies and inform cancer screening recommendations for those affected.

Researchers are studying familial cancer in children and their families to discover new genetic causes. This observational study focuses on families with a history of cancer to identify novel cancer-predisposing genes and genetic variants. The study aims to expand understanding of hereditary cancer predisposition by using next generation sequencing NGS technologies and establishing a linked data registry and biological sample repository. Participants provide blood samples, saliva, skin samples when needed, and occasionally leftover tumor or bone marrow samples. These biological specimens are stored in a biorepository and analyzed to detect gene changes potentially responsible for familial cancer. Participants may also be asked yearly for updated health and family history information if they agree to future contact. During the study, researchers collect medical and family histories along with biological samples to perform DNA sequencing and other genetic analyses. Samples are coded to protect identity and stored for current and future research. The primary outcome is identifying new cancer-related genes over up to 20 years. Participation involves sample collection and periodic updates, with ongoing confidentiality and long-term monitoring.

This research aims to improve understanding of pubertal development in patients with RASopathies, a group of genetic conditions affecting growth and development. The study focuses on describing the age when puberty starts, how it progresses in both males and females, and how puberty influences growth and final adult height. It also compares growth patterns between patients treated with growth hormone and those who are not. The study gathers data retrospectively from medical records of patients with a confirmed molecular diagnosis of RASopathy who have completed puberty. This includes collecting demographic information, prenatal history, medical and pubertal history, organ involvement, clinical evaluations of height and weight, growth rates, growth hormone treatment details, radiological assessments, laboratory tests, and genetic testing results. Patients are treated according to usual clinical practice as this is an observational study. Participants medical records will be reviewed to collect data on pubertal onset, hormone levels, peak growth rates, and statural gain during puberty. Researchers will measure outcomes like age at puberty onset, hormone concentrations, growth velocity, and final height. The study is conducted at a specialized regional center and involves patients aged 8 to 35 years with complete pubertal development. The study started in July 2024 and is expected to end in February 2025.

RASopathies are a group of developmental disorders caused by genetic changes affecting the RasMAPK pathway, which is important for cell cycle regulation and function. These disorders include several syndromes with unique but overlapping features such as facial differences, heart defects, skin abnormalities, cognitive delays, and a higher risk of cancers. This research aims to better understand these rare and often poorly characterized disorders by collecting biological samples and detailed clinical data from affected individuals and their relatives. The study collects various biological specimens like blood, saliva, tissue samples, and leftover clinical specimens from patients with suspected or confirmed RASopathies. These samples will be used for metabolic studies, genetic analysis, biomarker research, and to create immortalized cell lines. The study also gathers demographic information, medical histories, clinical test results, and survey data to build a long-term research database. Samples and data will be stored for future research and shared with other investigators studying RASopathies. Participants will provide biospecimens and clinical data over many years, with the aim to collect and store information for up to 50 years. Researchers will review medical records and neuropsychological evaluations, and participants will complete surveys to support ongoing research. The study includes both affected individuals and their unaffected relatives, and it allows for long-term monitoring of the natural history and molecular basis of these disorders.

This research focuses on RASopathy-associated hypertrophic cardiomyopathy RAS-CM, a serious condition with high risk of illness and death when it appears in infancy. The study aims to collect detailed clinical and genetic data from patients with RAS-CM to create a comprehensive data set that can be used as external control information for future clinical trials. It also seeks to gather natural history information to help select additional outcome measures for upcoming studies. Participants in this observational study are patients with a genetic diagnosis of congenital RASopathy and hypertrophic cardiomyopathy who experienced heart failure. The study involves collecting and reviewing past clinical records and genetic test results from patients admitted between January 2015 and June 2019. This retrospective data collection helps build a detailed understanding of the disease course without administering any new treatments. During the study, researchers will analyze hospital admissions, heart function imaging, and genetic information to define important outcomes such as the one-year survival rate without heart transplant in infants who developed congestive heart failure within six months of life. This data will support future clinical trials by providing baseline comparisons and insights into disease progression. The study does not involve direct treatment and will rely on existing medical records for all assessments.

RASopathies are genetic syndromes caused by changes in genes that regulate the RasMAPERK pathway, which plays a key role in development, organ formation, brain growth, and cell communication. These syndromes often involve multiple organs and can lead to growth delays, early aging, and blood-related cancers. Researchers are studying how common solid tumors non-blood cancers are in patients with RASopathies and are working to understand the molecular causes of these tumors. The study involves analyzing tissue samples from individuals with RASopathies using Next Generation Sequencing NGS. This diagnostic approach aims to characterize the molecular features of solid tumors found in these patients. The study is focused on reporting the prevalence of such tumors in a single center cohort and performing detailed genetic analysis on tumor samples. Participants will be monitored over five years to assess how often solid tumors occur and to gather molecular data from tumor tissues. The study collects clinical information and conducts genetic testing on tumor samples to help understand tumor development. This research is led by Fondazione Policlinico Universitario Agostino Gemelli IRCCS and is designed to improve knowledge about cancer risks and biology in people with RASopathies.