McCune-Albright Syndrome

Researchers are investigating targeted drug therapies for patients with vascular malformations that are resistant to standard treatments or for whom standard treatments are unsuitable. These vascular malformations are classified as either slow-flow or fast-flow types, driven by genetic changes in two specific signalling pathways. This phase II open-label trial aims to evaluate the effects of 48 weeks of treatment using either alpelisib for slow-flow vascular malformations with PI3K pathway mutations or mirdametinib for fast-flow vascular malformations with MAPK pathway mutations. Participants are divided into two treatment groups based on their vascular malformation type and genetic mutation. Those with slow-flow malformations and PI3K pathway mutations will receive alpelisib, an oral PI3-kinase inhibitor, for 48 weeks followed by a 24-week follow-up. Those with fast-flow malformations and MAPK pathway mutations will receive mirdametinib, an investigational oral MEK inhibitor, also for 48 weeks followed by 24 weeks of follow-up. Both treatments are given as monotherapy and involve genetic testing before enrollment to confirm mutations. Throughout the study, participants will undergo various assessments including symptom evaluations using the Vascular Malformation Patient Specific Outcome Measure (VM-PSOM) and OVAMA questionnaires, MRI scans to measure lesion size, and monitoring for adverse events. The primary outcome is the improvement in the most significant symptom after 48 weeks of treatment. Follow-up visits continue for 24 weeks after treatment ends to monitor ongoing effects and safety. The total participation duration for each patient is approximately 72 weeks.

Fibrous Dysplasia/McCune-Albright syndrome (FD/MAS) is a rare condition where normal bone is replaced by fibrous tissue, leading to weak bones that may cause fractures, pain, and decreased quality of life. Researchers are studying whether the medication Denosumab, given every three months, can improve symptoms and slow the progression of FD bone lesions. This study is a phase 4 trial aiming to evaluate clinical, radiological, and biochemical effects of Denosumab in adults with FD/MAS. Participants are randomly assigned to receive either Denosumab 120 mg or a placebo through injections under the skin at the start and after three months. After two injections, those with low pain scores stop the study treatment and continue usual care, while those with higher pain or lesion growth receive open-label Denosumab injections at six and nine months. This design allows comparison of Denosumab's effects against placebo initially and extended treatment for those needing it. Throughout the study, participants will have their pain levels, quality of life, physical activity, bone markers, lesion size and activity, bone density, and fracture occurrence monitored at multiple points up to 12 months. Weekly pain scores and medication use for pain relief will also be tracked. Safety assessments include watching for potential side effects like atypical femoral fractures. The total participation duration can last up to one year, including blinded and open-label treatment phases with regular clinical and imaging 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 study invites patients and families affected by fibrous dysplasia, McCune-Albright syndrome, and Mazabraud syndrome to share their experiences through a series of questionnaires. The study aims to answer key questions about how these conditions develop over time, patient experiences, diagnosis timing, treatment options, surgical techniques, social services, and the impact on quality of life and financial health. The project is led by Tovah Burstein and approved by an institutional review board to ensure ethical standards. Participants complete surveys designed with input from patients, parents, clinicians, and researchers. These surveys gather information on disease progression, symptoms like pain, mental health aspects such as depression and anxiety, stigma, treatment satisfaction, and the costs related to care. The study is observational, with no experimental treatments, and participation is free and fully remote, allowing people anywhere to contribute at their convenience. Participants provide information through surveys approximately every two years throughout the study duration. The research team monitors various outcomes including treatment satisfaction, pain, mental health, stigma, quality of life, and financial health. The study continues until 2028, with ongoing data collection to improve understanding of these rare conditions and help guide future research and support programs.

Fibrous dysplasia is a non-hereditary genetic condition characterized by areas of abnormal bone development where normal bone is replaced by fibrous tissue. This condition can vary widely in presentation, occurring as monostotic, polyostotic, or panostotic forms, and may be part of complex syndromes like McCune-Albright syndrome or Mazabraud syndrome. The condition arises from mutations in the GNAS gene, leading to a genetic mosaic state in affected individuals. This research aims to provide a detailed evaluation of patient characteristics, hospitalizations, and interventions, with a study group of over 200 patients to offer a comprehensive understanding of the condition and its genetic impacts. The study is observational and includes patients with fibrous dysplasia, McCune-Albright syndrome, and Mazabraud syndrome who have available clinical, radiological, surgical, and tissue biospecimen data. Two main patient groups are studied: those with clinical and surgical data and those with available tissue samples for molecular analysis. This approach allows for a broad assessment of the clinical features and genetic correlations related to these conditions. Participants' involvement includes the collection and analysis of clinical and radiological data, surgical procedure descriptions, and molecular studies of tissue samples. Researchers monitor surgical procedures, clinical features, genotype-phenotype correlations, post-intervention complications, and pain over four years. This detailed data collection aims to improve understanding of the disease's manifestations and outcomes, with ongoing observation throughout the study period.

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 an observational study to better understand the natural history of imprinting disorders (IDs) through their metabolic profiles in both adults and children. The study aims to identify common metabolic profiles among various imprinted diseases, assess their impact, associated metabolic risks, and explore their use for clinical classification, prognosis, and treatment approaches for IDs. The study is sponsored by the Institut National de la Santé Et de la Recherche Médicale, France. This study follows patients diagnosed with imprinting disorders confirmed by molecular diagnosis, regardless of disease severity. Participants include both adults and children who have provided informed consent or whose guardians have consented. The study does not involve any treatment interventions but focuses on gathering detailed clinical, genetic, biological, and morphometric data over time. Participants will be followed for an average of 10 years, during which researchers will collect information on clinical features, genetic and biological characteristics, and body measurements. The study will also monitor metabolic abnormalities and risks such as obesity, diabetes, cardiovascular disease, and metabolic syndrome. Quality-of-life scores and genetic mutation transmission within families will be analyzed. This long-term observation will help clarify therapeutic approaches and improve understanding of imprinting disorders.

Polyostotic fibrous dysplasia (PFD) is a rare disorder affecting multiple skeletal sites where normal bone is replaced by abnormal fibrous tissue or mechanically weak bone. It can occur alone or with McCune-Albright Syndrome (MAS), which includes skin pigmentation and early puberty. The bone lesions can cause pain, deformity, fractures, and nerve compression. The natural progression of PFD/MAS is not well understood, and there are no established systemic treatments for the bone disease. This observational study aims to define the natural history of PFD/MAS by following affected individuals over time and studying tissue samples in the lab. Participants in this study include those with known or suspected PFD or MAS. Researchers will collect clinical data during visits and obtain tissue samples when available, including waste tissue from surgeries. Lab analyses will focus on understanding the bone biology of affected cells, identifying mutation patterns, studying bone formation processes, and exploring the disease's endocrine aspects. The goal is to better predict lesion behavior and develop future research directions related to PFD and MAS. During the study, participants will have clinical evaluations and may provide tissue samples for research. Data collected will help characterize lesion growth, stability, and progression, as well as endocrinopathies associated with MAS. The primary outcome is to gather clinical and laboratory information to define disease natural history. Eligible participants may also be referred to other research protocols. The study is ongoing and open to individuals aged 1 day and older, with no gender or racial restrictions.