Microcephaly

Researchers are creating a database of healthy adult subjects aged 18 to 65 years to study brain structure and function using advanced imaging techniques. This project, part of the European Human Brain Project, focuses on healthy individuals to better understand brain activity and metabolism through a multimodal approach involving MRI, PET, and electrophysiology. The goal is to provide valuable data for scientific collaboration on epilepsy and brain health. Participants will undergo a 18F-FDG PET brain imaging exam, which measures glucose metabolism in the brain by using a small amount of radioactive tracer injected intravenously. The scan lasts about 45 minutes and captures a three-dimensional image at rest, allowing researchers to quantify brain glucose consumption and connectivity. This is a non-therapeutic study involving a single imaging procedure performed at baseline, with a follow-up measurement planned 24 months later. During the study, participants will be monitored through imaging and assessments of cerebral glucose consumption and metabolic connectivity at baseline and after 24 months. The PET scans are part of routine clinical procedures with established safety profiles, and all participants must provide informed consent. The study lasts over two years, including the initial scan and long-term follow-up, aiming to enhance understanding of healthy brain metabolism and function.

Researchers are studying individuals with MEHMO syndrome or related eIF2-pathway conditions, which involve symptoms such as intellectual disability, seizures, hormone and blood sugar irregularities, and reduced motor skills. This observational natural history study aims to better understand these rare conditions by identifying clinical and biochemical markers to track disease progression and to improve knowledge about their course and impact. Participants include those diagnosed with MEHMO syndrome or related disorders, carriers of EIF2S3-related variants, and unaffected family members. The study involves regular health assessments, imaging tests, laboratory evaluations, and collection of biological samples including blood, urine, spinal fluid, and skin biopsies. It follows individuals over time to gather comprehensive data and biological materials. During the study, participants will undergo evaluations of their general health and disease symptoms, imaging exams, and various laboratory tests. Researchers will monitor clinical signs and fluid biomarkers to develop a severity rating scale and classification system. The study also aims to build a repository of data and samples for future research. This observational study does not involve any treatment but focuses on detailed monitoring to support future therapeutic development.

Researchers are evaluating MELPIDA, a gene therapy product, for treating Spastic Paraplegia Type 50 (SPG50), an ultra-rare genetic disorder causing progressive neurodegeneration, spasticity, intellectual disability, and severe motor impairment. SPG50 results from mutations in the AP4M1 gene, leading to loss of function in the adaptor protein complex 4, which affects critical protein trafficking in neuronal cells. This trial aims to assess the safety and tolerability of a single intrathecal dose of MELPIDA and explore its effects on disease burden in affected children. The study involves administering MELPIDA, which delivers a functional human AP4M1 gene via a recombinant adeno-associated virus (AAV9) through an injection into the spinal canal. This is an open-label, phase 1/2 trial focusing on a single treatment dose. Participants are children aged 4 months to 10 years with confirmed SPG50. The trial monitors safety by tracking treatment-related adverse and serious adverse events, while also evaluating efficacy through measures of spasticity using the Modified Ashworth and Tardieu scales over a 60-month period. Participants will be closely observed for up to five years after treatment to monitor any toxicities or changes in spasticity and disease progression. Assessments include clinical exams and neurological evaluations to measure motor function and spasticity levels. Safety monitoring involves tracking laboratory values and any adverse events. The long follow-up allows researchers to gather detailed information on the treatment's impact over time and the natural course of SPG50 in treated children.

Researchers are studying children diagnosed with Microphthalmia, Anophthalmia, and Coloboma (MAC), which are congenital eye defects affecting eye size and structure. The study aims to understand the physical traits of these conditions and how genetic changes contribute to the risk of developing MAC. The overall goal is to improve prevention and clinical care for affected children. Participants include children diagnosed with MAC, their parents, and siblings. The study collects detailed physical and genetic information by collaborating with various registries and hospitals. Researchers use resources from newborn screening programs and specialized NIH centers to identify and analyze genetic variants linked to MAC. Families involved in the study will provide data through medical evaluations and genetic testing. The research team will review physical characteristics and genetic information to better define MAC and its genetic causes. This observational study is ongoing, and participants may be followed until the study ends in 2032, with no interventions or treatments required.

This research focuses on congenital malformations of the eye, including microphthalmia, anophthalmia, aniridia, and anterior segment dysgenesis such as Peters and Axenfeld-Rieger anomalies. These conditions often come with extra-ocular features and intellectual disability, but much is still unknown about their visual outcomes and neurological effects. The study aims to include a range of malformations considered part of a phenotypic continuum and to follow affected children for 10 years to better understand their eye and neurological development, as well as other medical events. Researchers also want to identify factors linked to better or worse visual and neurological outcomes. The study is observational and will include both retrospective and prospective data collection. It involves children and adults with congenital eye defects. Participants will undergo various eye examinations such as visual acuity tests with refraction under cycloplegia, binocular vision assessments by orthoptists, slit lamp and fundus exams, ultrasound measurements of eyeball length, and several ocular imaging techniques like videotopography, ultrabiomicroscopy, and macular optical coherence tomography. Neurological evaluations will also be performed using standard procedures appropriate for age. These assessments will occur over multiple visits depending on the participant's age. Participants will be monitored through scheduled visits with up to three visits for children under 6 years, two visits for children aged 6 to under 8 years, and one visit for those 8 years and older. During these visits, visual and neurological functions will be carefully evaluated alongside questionnaires on quality of life and presence of extraocular malformations. The study aims to improve understanding of these rare conditions to enhance patient management and care over time.

Researchers are investigating how sleep disorders are related to structural differences in children with Chiari Malformation Types 1 and 2. The study aims to understand the connection between sleep-disordered breathing (SDB) severity and measurements of airways, cranial base openings, and the volume of the back part of the skull. This study focuses on pediatric patients to provide insights into how these brain malformations may impact breathing during sleep. Participants will undergo diagnostic tests including magnetic resonance imaging (MRI) to measure the volume of the posterior cranial fossae, airway size, and cranial base foramina area. They will also have polysomnographic evaluations to assess the presence and type of sleep-disordered breathing, distinguishing between central and obstructive origins. The study compares two groups of children with Chiari Malformation Type 1 and Type 2. During the study, children will be closely monitored through these imaging and sleep tests over a period of three years. Researchers will measure the prevalence of sleep-disordered breathing and analyze how it relates to anatomical differences in the brain and airway structures. The study includes clinical evaluations and informed consent processes, allowing careful observation of sleep breathing patterns and brain structure relationships in this young population.

Researchers are studying the genetics behind a group of eye conditions called microphthalmia, anophthalmia, and uveal coloboma (MAC), which are developmental problems where the eye does not form properly. These conditions can lead to various eye issues including blindness. The study aims to understand the eye and other body-related features in people with MAC, identify risk factors in their relatives, and create a collection of DNA samples for future research. Participants include individuals aged one year or older who either have MAC or are close relatives without symptoms, such as parents or siblings. The study involves a full eye exam and physical exam appropriate to the participant's age. Those with MAC may also have additional tests like imaging and hearing assessments. All participants will provide samples of blood, cheek swab, saliva, or DNA for genetic testing. During the study, participants will undergo thorough medical and eye exams, have their medical history reviewed, and provide biological samples. Researchers will analyze the data and samples collected to better understand the genetics and associations of MAC. The study will enroll up to 600 participants over fifteen years, with ongoing analysis of test results to improve knowledge of these eye conditions.

Researchers are investigating whether the antiviral drug Letermovir is more effective than Valaciclovir in treating pregnant women carrying fetuses infected with cytomegalovirus (CMV) from a first trimester infection. This study focuses on improving outcomes by reducing viral replication in fetuses to increase the number of neonates with negative CMV PCR results at birth, which may lower the risk of neurological and hearing problems that often occur with congenital CMV. The trial is a Phase 3 randomized study comparing these two antiviral treatments. Participants will receive either daily Letermovir tablets (240 mg) plus a placebo for Valaciclovir or daily Valaciclovir (8 grams total per day) plus a placebo for Letermovir until delivery or termination of pregnancy. The study includes monitoring fetal health via ultrasound and MRI at baseline and follow-up visits at weeks 2, 4, and 6 of treatment. The trial also assesses changes in viral load in various samples, including blood, amniotic fluid, saliva, and urine, and measures drug concentrations in cord blood, placenta, and neonatal blood. During the study, participants will undergo regular clinical visits with evaluations of maternal and fetal health, laboratory tests, imaging studies, and compliance checks up to 39 weeks of gestation. Researchers will monitor neonatal outcomes at birth and track the development of long-term sequelae up to two years of age. Safety assessments include maternal blood counts and organ function tests. The primary outcome is the proportion of neonates with negative CMV PCR in blood collected within the first day of life or at termination of pregnancy. Secondary outcomes include birthweight, placental weight, and the number and type of long-term complications.

Researchers are collecting information from individuals diagnosed with various forms of microcephalic primordial dwarfism and related conditions through a registry. The goal is to better understand these rare conditions, identify risk factors, and ultimately improve care and quality of life for those affected. This is an observational study focused on gathering data from medical records without additional procedures or visits. The study involves reviewing existing medical records, including specialist evaluations, surgical reports, blood and urine test results, genetic testing, and imaging such as x-rays, CT, MRI, or MRA scans. No new tests or clinic visits are required for participation. All data is collected and stored solely from the participant's medical history. Participants will not be required to attend any study visits or undergo special testing. The research team will analyze the collected information to characterize the natural history of these forms of primordial dwarfism over a period of five years. The study is designed to be minimally invasive, relying entirely on existing medical information without impacting the participant's routine care.

Researchers are conducting a patient registry and natural history study called Coordination of Rare Diseases at Sanford (CoRDS) to support research on rare diseases. CoRDS is an international registry that connects patients with rare, undiagnosed, or uncommon diseases to researchers studying over 7,000 rare diseases. This program aims to help advance treatments and cures by facilitating easy collaboration between patients, advocacy groups, and researchers. It is based at Sanford Research in Sioux Falls, South Dakota, and is free for patients to join and for researchers to access. Participants provide contact, sociodemographic, and health information, which is entered into CoRDS and linked to a unique coded identifier. Examples of collected data include name, mailing address, phone number, email, date and place of birth, sex, gender, ethnicity, family history, and diagnosis-related information. De-identified information may be shared with approved researchers after review by an Institutional Review Board and expert panel. Some data may also be shared with other databases and patient advocacy groups, with protections to prevent misuse for research purposes. Participants are contacted yearly to confirm continued participation and to update their information. If a parent or legal guardian consents for a minor, the participant will be contacted at age 18 to provide their own consent. The primary goal is to accelerate research by connecting individuals interested in rare disease research with scientists over a long period of up to 100 years. There is no treatment given, as this is an observational registry study.