Costello Syndrome

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.

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 investigates hereditary cancer predisposition by identifying novel genes and genetic variants that may contribute to familial cancer. While hereditary factors are known to cause some cancers, many causes remain unknown. The study focuses on families with cancer clustering, aiming to better understand genetic links to improve diagnosis and care for hereditary cancer. Participants provide blood or saliva samples and medical and family history information. Leftover tumor samples may also be collected when available. Samples are stored in a biorepository and studied using next generation sequencing to detect gene changes. Some participants may provide skin samples if they had bone marrow transplants without available pre-transplant DNA. Participants may be contacted yearly for health and family history updates. During the study, researchers analyze DNA and other biological samples to find mutations linked to cancer. This includes sequencing, genetic and cellular studies, and possibly stem cell analyses. Personal information is removed, and samples remain in the repository for future research. The primary outcome is identifying new cancer predisposing genes, with follow-up of up to 20 years from study start.

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 Ras/MAPK 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 Ras/MAP/ERK 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.

Researchers are studying the thyroid health and bone metabolism in patients diagnosed with RASopathies, a group of genetic conditions confirmed by specific gene analysis. The main goal is to find out how common thyroid diseases and structural abnormalities of the thyroid gland are in these patients compared to the general population. They are also investigating the link between vitamin D deficiency or other bone metabolism issues and thyroid problems in this group. Participants will have blood tests to assess thyroid function, autoimmune markers, and bone metabolism indicators such as calcium, phosphorus, and vitamin D levels. They will also undergo a detailed color Doppler ultrasound of the thyroid gland to examine its size, structure, blood flow, and any nodules or lymph node changes. During the study, researchers will measure the number of patients with thyroid and bone abnormalities over six months. The study involves patients aged 3 to 25 years with genetically confirmed RASopathies. The overall participation includes clinical assessments, laboratory tests, and imaging to compare findings with those in the general population, providing a comprehensive view of these conditions.