Deletion/Microduplication Syndrome

Researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug ION440 in people with Methyl CpG Binding Protein 2 MECP2 Duplication Syndrome MDS. This phase 1-2 randomized, double-blind, sham-controlled study includes both pediatric and adult participants to better understand how ION440 affects this rare genetic condition. The study is sponsored by Ionis Pharmaceuticals, Inc. and aims to carefully monitor treatment impacts over time. Participants will be randomly assigned to receive one of three different doses of ION440 or a sham procedure during the first part of the study, which lasts about 36 weeks. ION440 is given by injection into the spinal fluid intrathecal bolus. After completing the first part, participants may enter a second open-label extension lasting up to approximately 156 weeks, where they receive the same dose of ION440 as before. The study includes two age groups children aged 2 to 7 years and participants aged 8 to 65 years. The dosing groups are evaluated sequentially, starting with the older group. During the study, participants will undergo physical and neurological exams, vital sign checks, lab tests, electrocardiograms, and monitoring for any adverse effects. Blood and cerebrospinal fluid samples will be collected to measure drug levels. The study will assess the number of participants experiencing treatment-related side effects and changes in health markers over both the initial 36-week period and the longer extension. Participants are expected to complete all study visits and procedures to support these evaluations, which together may last more than three years.

Myelodysplastic syndromes MDS are chronic blood disorders marked by ineffective blood cell production and normal marrow richness. MDS affects mostly older adults and carries a risk of progressing to acute leukemia in 30 to 40% of cases. This study aims to build a biocollection to better understand the clinical and biological markers that predict progression to acute myeloid leukemia by studying subgroups of MDS patients with different genetic and chromosomal characteristics. The study involves collecting biological samples and clinical data from patients diagnosed with or suspected of having MDS. Researchers will investigate specific genetic mutations affecting RNA splicing, particularly mutations in the SF3B1 gene, and chromosomal deletions such as 5q deletion. The study focuses on three scientific projects exploring splicing abnormalities, the impact of chromosomal deletions on disease progression, and the clonal architecture in patients progressing to leukemia. Participants will provide biological material collected at the research center, and clinical data will be gathered during diagnosis and follow-up visits. The research team will perform detailed molecular analyses, including RNA sequencing, protein detection, and enzymatic studies to understand the disease mechanisms. The primary outcome is an epidemiologic study of the MDS cohort over five years, aiming to identify prognostic markers and improve understanding of MDS progression. Participation may last several years, with ongoing data and sample collection.

Researchers are studying Canadian cancer patients who have rare genetic changes in their tumors, such as alterations in genes like ALK, EGFR, ROS1, BRAF, and KRAS G12C. These rare molecular alterations can affect how the cancer responds to certain targeted drugs called tyrosine kinase inhibitors TKIs. The study aims to better understand the natural history of these cancers and compare treatment outcomes, including side effects and patient-reported experiences, across different therapies. The study observes cancer patients who have received or are currently receiving TKIs or other targeted therapies. It includes three groups living patients with confirmed rare molecular alterations, deceased patients with such alterations, and a comparator group of cancer patients without these rare changes. Patient-reported outcomes are collected through surveys at baseline and every three months, especially when treatments change. Participants provide molecular testing reports and complete quality of life questionnaires regularly for up to 10 years. Researchers track progression-free survival or overall survival, the development of brain metastases, and economic impacts related to treatment. The study collects data from medical records and patient surveys to understand treatment patterns, effectiveness, and quality of life in the real-world Canadian context.

Researchers at the University of Texas Health Science Center at San Antonio are studying individuals with chromosome 18 abnormalities to better understand the genetic causes and effects of these conditions. The study aims to identify how growth hormone deficiency and other genetic factors impact brain structure and cognitive function, as well as physical and behavioral traits. The goal is to provide comprehensive medical and educational resources, perform clinical and basic research, and develop treatments to improve the lives of affected individuals. Participants undergo various evaluations including genetic testing of DNA from subjects and their parents to determine genotype. Clinical assessments include testing growth hormone and other hormone levels, psychiatric and neuropsychological evaluations, audiology and ENT exams, brain MRI scans, genetic dysmorphology, neurology, dental, speech pathology, gastrointestinal, orthopedic, and ophthalmologic examinations. These assessments are longitudinal, with participants of a wide age range, and not all tests apply to every participant at every visit. Participants will be involved in thorough clinical evaluations and multiple specialized exams over time to gather detailed health data. These include hormone tests, brain imaging, behavioral and cognitive assessments, and physical exams. Researchers will monitor growth hormone status and other health markers to understand the conditions impact. The study is ongoing and designed to provide long-term data to guide future treatments and support. Total participation time varies depending on individual assessments and follow-up needs.

This research focuses on patients with a rare condition called Chromosome 9P Deletion Syndrome, where a part of chromosome 9 is missing. Because only about 200 cases have been reported in medical literature, the study aims to better understand the link between the specific deleted genes and the diverse physical traits seen in affected individuals. Researchers will use advanced genome sequencing techniques to analyze the size and location of the chromosome deletion and examine the genetic background of each patient. Participants will undergo whole genome sequencing to gather detailed genetic information. Alongside this, they will complete a thorough questionnaire and provide a biospecimen sample for analysis. Family members, such as parents and siblings, may also participate to help clarify how genetic background influences physical characteristics related to the condition. During the study, participants will provide medical information through questionnaires and biospecimens, which researchers will use to identify correlations between genetic changes and physical traits. The main outcome measured is the relationship between genotype and phenotype, with preliminary results expected as enrollment increases. The study is observational, and participants involvement will mainly consist of providing samples and information for research purposes.

Researchers are studying RAI1-related disorders, including Smith-Magenis syndrome and Potocki-Lupski Syndrome, to better understand disease features and identify clinical, neurophysiological, and molecular biomarkers. These biomarkers can help diagnose, monitor treatment response, and track disease progression. Currently, there are no genetic-based treatments or established biomarkers for these conditions, so this observational and laboratory study aims to fill that gap. Participants include patients with RAI1-related disorders and healthy family members as controls. Patients will undergo clinical examinations, blood draws, and some may have a sleep study or optional skin biopsy. The sleep study records brain waves, oxygen levels, heart rate, and movements during an overnight stay. Blood samples will be used for molecular biomarker research, and skin biopsies may create cell lines for laboratory study. Participants will complete a one-time visit that may include overnight monitoring for the sleep study. Assessments include medical history, physical and neurological exams, vital signs, sleep and EEG studies, blood draws, and optional skin biopsies. Researchers will compare patient and control blood samples to identify biomarkers. The study measures neurological findings, sleep abnormalities, and molecular markers related to RAI1. Participation may last one day with possible additional visits if needed.

This research aims to build a large platform combining clinical information and biological specimen banks for fetuses and infants diagnosed with intrauterine growth restriction IUGR or congenital anomalies. These conditions are significant causes of infant and childhood death, and this study seeks to understand their occurrence, progression, and relationship from before birth through early childhood. The goal is to provide a foundation for accurate diagnosis, precision treatment, and careful management of these conditions. Pregnant women and infants diagnosed with IUGR or various congenital anomalies including structural and chromosomal anomalies are enrolled. Routine obstetrical ultrasounds monitor fetal growth, and detailed maternal information, including dietary habits and exposures, is collected. After birth, infants receive appropriate treatments and regular physical and neurological examinations. Biological samples such as maternal blood, placenta, cord blood, infant blood, urine, stool, and tissues are collected and stored for research. Genetic testing is also conducted to explore disease causes and guide treatment. Participants undergo ongoing assessments including growth and development measurements, clinical outcome tracking, and evaluation of treatment effects on hospitalization and health. Data are collected via intelligent extraction platforms and analyzed using machine learning and statistical methods to improve prenatal diagnosis accuracy and identify prognostic markers. The study includes follow-ups up to several years to observe recovery and quality of life, supporting improved prevention and care strategies.

Researchers are studying adolescent idiopathic scoliosis AIS, a condition where the spine curves during the adolescent growth spurt, but its exact cause remains unclear. The study focuses on girls and boys at higher risk for scoliosis development, including those with family history and those with 22q11.2 deletion syndrome 22q11.2DS. The goal is to understand differences in spine growth and changes before and during AIS onset using new non-radiation imaging methods. This observational study follows two groups one of adolescent girls aged 8-10 years with family members diagnosed with AIS, and another of girls and boys aged 8-11 years diagnosed with 22q11.2DS. Participants will undergo spinal MRI and 3D ultrasound scans at multiple time points from ages 8 or 9 to 15 or 16, depending on gender. A hand radiograph for skeletal maturity assessment will be done once. The study aims to track anatomical spine changes over time without any intervention. Participants will have spinal MR imaging of the thoracic and lumbar regions at five scheduled ages to evaluate changes in spinal anatomy, including segmental rotation and disc morphology. Other assessments include spinal alignment, vertebrae and disc volumes, and nucleus pulposus shift. These imaging tests are radiation-free and repeated over several years to create a detailed longitudinal dataset. Parents will provide consent, and the study will monitor growth and scoliosis development until participants reach mid-adolescence.

22q11.2 deletion syndrome is a genetic disorder caused by the loss of a small part of chromosome 22, affecting many parts of the body and leading to conditions such as heart defects, immune deficiencies, kidney issues, hearing loss, facial deformities, developmental delays, learning disabilities, and increased risk of mental illnesses like schizophrenia, depression, anxiety, and bipolar disorder. Severity varies widely, with some people showing many symptoms and others very few, sometimes without even knowing they have the syndrome. This research aims to identify genetic variations that influence the severity of 22q11.2 deletion syndrome by analyzing DNA from affected individuals. Participants in this observational study will provide genetic material collected from blood or saliva during one study visit. The study will analyze the DNA sequences to find genetic differences that might explain the varying severity of the disorder. This single-visit approach allows researchers to gather important genetic information without requiring ongoing treatment or intervention. During the single study visit, participants will provide a blood or saliva sample for DNA analysis. The study will focus on collecting and examining genetic data to understand how different genetic factors may impact the disorders severity. There are no treatments or medications involved, and participants will not have additional visits related to this study. The total involvement requires only one visit for sample collection and data gathering.

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.