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 like intellectual delay, seizures, hormone and blood sugar abnormalities, and reduced motor skills. This observational natural history study aims to better understand the disease progression and identify markers to monitor these rare conditions, as no treatments currently exist. The study also seeks to develop tools for diagnosis, severity rating, and future research resources. Participants include affected individuals, carriers, and unaffected family members. The study involves general health assessments, imaging, laboratory tests, and collection of samples such as blood, urine, spinal fluid, and skin biopsies. Data and biomaterials will be collected longitudinally to compare affected, carrier, and unaffected groups. Throughout the study, participants will undergo evaluations to characterize disease presentation and identify biomarkers. Researchers will assess the feasibility of study procedures and develop severity scales. A repository of participant data and samples will be created to support future research. The study is ongoing and follows participants over an extended period with regular assessments.

This research aims to evaluate MELPIDA, a gene therapy for treating Spastic Paraplegia Type 50 SPG50, a rare inherited neurodegenerative disorder caused by mutations in the AP4M1 gene. SPG50 leads to progressive muscle stiffness, cognitive impairment, and severe disability starting in early childhood, with no current treatments available. The study focuses on safety and tolerability, as well as exploring effects on disease severity in affected children. MELPIDA delivers a functional copy of the AP4M1 gene using a single intrathecal injection of a recombinant adeno-associated virus AAV vector. The therapy targets neuronal cells to counteract neuronal loss caused by the disease. Participants will receive this gene therapy as the only treatment arm. The study follows an open-label design and lasts up to five years to assess long-term safety and potential clinical benefits. Participants will be closely monitored with evaluations including neurological exams and spasticity assessments using the Modified Ashworth and Tardieu scales. Safety will be measured by tracking adverse events related to treatment over 60 months. The trial includes genetic confirmation, clinical assessments, and long-term follow-up to understand the therapys impact on disease progression and patient health. Overall participation may extend up to five years.

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.

Researchers are studying congenital malformations of the eye, which include developmental defects like microphthalmia, anophthalmia, aniridia, and various anterior segment abnormalities. These conditions may affect one or both eyes and often come with extra-ocular features and intellectual disabilities. The study aims to improve understanding of visual and neurological outcomes over a 10-year follow-up, identifying factors related to better or worse prognosis and improving patient care. This observational study includes children and adults with these eye malformations. The study involves detailed eye examinations such as visual acuity tests, binocular vision assessments, slit lamp and fundus exams, ultrasound measurements, and advanced imaging techniques like OCT. Neurological evaluations are also performed. Patients will be assessed up to three times depending on their age and condition. Participants will undergo various evaluations including quality of life questionnaires and monitoring of ocular and extraocular malformations. Visual and neurological functions will be tracked over multiple visits. The study collects comprehensive data to help predict disease progression and improve management. The total duration can extend up to 10 years with periodic assessments according to patient age.

Researchers are studying the genetics of microphthalmia, anophthalmia, and uveal coloboma MAC, conditions where the eye does not form normally and can lead to vision problems or blindness. This study aims to understand the eye and systemic features seen in people with MAC, identify risk factors in their relatives, and create a repository of genetic material for future research. Approximately 600 participants aged one year and older, including those affected by MAC and their close unaffected relatives, will take part over about fifteen years. Participants will undergo a full eye exam appropriate for their age, a physical exam, and provide medical history. Those with MAC may have additional tests like imaging and hearing assessments. All participants will provide blood, cheek swab, saliva, or DNA samples for genetic analysis. Some participants may be referred from a related genetic epidemiology study. During the study, participants will be evaluated with eye and physical exams, and provide samples for genetic testing. Researchers will analyze tests, data, and samples to better understand the genetics and associated features of MAC. The study is observational and does not involve treatment. Participation may last many years as data is collected to investigate genetic causes and related risk factors.

Researchers are evaluating the effects of prenatal choline supplementation on infant growth and brain development in pregnant women who abstain from alcohol. This pilot phase 2 study compares the outcomes of choline supplementation versus placebo in healthy pregnant women without prenatal alcohol exposure, aiming to understand potential benefits on infant recognition memory, postnatal growth, and neurobehavioral development. Participants will receive either 2 grams of choline cation daily or a placebo beverage identical in appearance, taste, and smell. The study follows a randomized, double-blind, placebo-controlled design and plans to enroll 50 pregnant women with singleton pregnancies who have abstained from alcohol. The protocol mirrors a previous study involving heavy-drinking pregnant women, allowing comparison of cholines effects in non-drinking mothers. During the study, infants will be assessed for recognition memory at 12 months and growth measurements weight, head circumference, and length at 6.5 months. Additional evaluations include infant information processing speed and eyeblink conditioning. Researchers will monitor participants through scheduled visits to collect developmental data, track adherence, and ensure safety. The studys total duration extends through infant assessments up to 12 months of age.

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 participants 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 participants 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.