Clinical trials

Background: Premature ovarian insufficiency (POI) is a condition in which women under the age of 40 years have absent or irregular menstrual cycles. POI can cause infertility, signs of menopause, osteoporosis, and other symptoms. Hormone replacement therapy (HRT) is a treatment that gives women extra hormones, such as estrogen and progesterone. HRT works well in adult women. Researchers want to find the most effective doses and regimens for adolescents. Objective: To monitor the effects of HRT on adolescents with POI. Eligibility: Female adolescents aged 11 to 19 years diagnosed with POI. Healthy volunteers are also needed. Design: All participants will have clinic visits every 6 months for 2 years. Each visit may last 2 days. Each visit may include: Blood and urine tests. A test of their heart function. A test to measure the stiffness of their blood vessels. Participants will lie flat with a blood pressure cuff on a leg and a meter on the neck while the cuff inflates. A test of their grip strength. Participants will squeeze a handheld device as hard as they can. Two scans to measure bone density. For one, participants will lie on a table while a scanner passes along their body. For the other, participants will sit in a chair and insert their forearm, then their lower leg, into a scanner. A test to measure skin pigmentation. Participants' skin will be touched lightly with a device. An optional visual exam of the vagina. Some vaginal fluid may also be collected with a cotton swab/cytobrush. Participants with POI will receive HRT. They will be given estrogen patches and progesterone pills.

Background: \- Studies show that many factors affect children's eating behavior and health. These include sleep, mood, thinking skills, and genetics. Studying children over time may identify children at higher risk for eating-related health concerns. Objective: \- To understand how genes and environment influence eating behavior and health over time. Eligibility: \- Children ages 8-17 in good general health. Design: * Screening visit 1: Medical history, physical exam, body measurements, and questions. * 14 days: Participants will wear a wrist monitor and answer smartphone prompts about eating and mood. They may give a stool sample. * Screening visit 2: * Body measurements. * Saliva, urine, and blood samples. * Heart tests. * Meals provided (after fasting overnight). * Questionnaires and interview. * Behavior, thinking, and exercise tests. * X-ray of left wrist and full body.\<TAB\> * Some parents may have medical history, physical exam, and questions at screening visits. They may answer questions at the yearly visits. * Participants will have up to 6 yearly visits. They will give a urine sample and body measurements, and repeat the X-rays. They will have questions and behavior and thinking tasks. They may give stool samples. Visits will range from 3 to 8 hours. * Participants may choose to participate in other studies: * Stress and Hormones, 1 visit: While resting, participants will give saliva samples and have their heart monitored. Then they will do math. They will repeat the resting part, then do a computer task. * Brain Imaging, 2 visits: Twice, participants will perform tasks with a magnetic cone on their head then answer questions. Once, they will have an MRI, lying still in a scanner with a coil on their head. Before the first visit, participants will collect at-home saliva samples once a day for three days. During both visits, participants will perform tasks and answer questions that gauge their thinking skills and mood. * Experiment 3 (sleep/fatigue): Participants will complete 2 additional visits. During these visits, participants will complete a task on the computer for 2 hours, or watch a movie for two hours. After completion of the task/movie, they will answer questions and be provided with food. Participants will be compensated for the time and inconvenience involved with completing study procedures. ...

This study will evaluate clinical and laboratory tests that might be useful in determining if an investigational drug can slow the progression of Niemann-Pick Disease, Type C (NPC), a genetic disorder that results in progressive loss of nervous system function. The study will: 1) look for a clinical or biochemical marker that can be used as a measure of response to treatment, and 2) define the rate of progression of biochemical marker abnormalities in a group of NPC patients who will later be invited to enroll in a treatment trial. Patients of any age with NPC may be eligible for this study. Participants undergo the following procedures every 6 months during 4- to 5-day admissions at the NIH Clinical Center. * Medical evaluation, including medical history, physical exam, neurological exam, neuropsychometric evaluation, and blood and urine tests. * Lumbar puncture (spinal tap): A sample of cerebrospinal fluid (CSF), the fluid that bathes the brain and spinal cord, is obtained for study. After administration of a local anesthetic, a small needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle. * Eye exam and eye movement study: The pupils of the eye are dilated to examine the structures of the eyes. For the eye movement study a special contact lens is placed on the eye and the patient looks at a series of target light spots moving on a screen. * Hearing tests. * Electroretinography (in patients who can cooperate with the test) to measure the function of the retina. Before the test, the patient's pupils are dilated and an electrode (small silver disk) is taped to the forehead. The patient sits in a dark room for 30 minutes and then a special contact lens is placed on one eye after it has been numbed with drops. The contact lens senses small electrical signals generated by the retina when lights flash. During the ERG recording, the eye is stimulated with flashes of light projected inside a hollow sphere. After the test, a full eye exam is done and photographs of the retina are taken. * Magnetic resonance imaging (MRI): This test uses a magnetic field and radio waves to produce images of the brain and obtain information about brain chemicals. The patient lies on a table that can slide in and out of the scanner (a narrow cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. Patients who cannot remain still in the scanner may be sedated for the test. * Psychometric testing: Patients complete questionnaires. * Photographs of the patient may be taken for use in teaching sessions or scientific presentations or publications, with the patient's consent. Patients may be recognizable, but are not identified by name. * Pregnancy test in all female patients over 10 years of age at the beginning of each admission to the Clinical Center.

This study will evaluate and gather information in patients with genetic causes of too much androgen (male-like hormone) in order to better understand the effects of too much androgen and describe problems associated with it. Too much androgen in childhood, if untreated, results in rapid growth and early puberty with early cessation of growth and short stature in adulthood. Too much androgen in adulthood may result in infertility, and women may have excess facial hair, acne and a more male-like appearance. Excess androgen may also affect mood and behavior and possibly the secretion of other hormones, such as insulin. Two genetic diseases that result in early childhood androgen excess are congenital adrenal hyperplasia (CAH) and familial male-limited precocious puberty (FMPP). Patients with known or suspected CAH due to 21-hydroxylase deficiency, 11- hydroxylase deficiency, or 3-beta-hydroxysteroid dehydrogenase deficiency and males with known or suspected FMPP may be eligible for this study. Patients with both classic and non-classic CAH are eligible, and patients with androgen excess of unknown cause may be eligible. Participants undergo the following procedures: * Medical history and physical examination. * Fasting blood tests for analysis of hormones, blood chemistries including blood sugar and cardiovascular risk factors such as lipids. * Oral glucose tolerance test for patients with elevated insulin levels. For this test, a catheter (plastic tube) is placed in a vein in the patient's arm. The patient drinks a sugar-containing fluid and blood samples are collected through the catheter at intervals starting with drinking the solution, and then 30, 60 and 120 minutes after drinking the solution. * 24-hour urine collection to measure hormone levels in the urine. * DNA testing for patients with 21-hydroxylase deficiency to help identify the type of genetic mutation responsible for the disease. * X-ray of the left hand to measure bone age in growing children. The x-ray is used to determine how far into puberty the child is and how much growth potential is left in the bones. * A pelvic ultrasound in females and testicular ultrasound in males to evaluate the size and development of the gonads (ovaries in females and testes in males). * Cognitive and psychological tests, including an IQ test and evaluation of memory, achievement and behavior. * Other tests and evaluations based on medical need. The schedule for these procedures varies. In a part of the study involving only patients with CAH, growing children are evaluated twice (once in childhood and once after reaching adult height), and adults are evaluated once. In another part of the study involving patients with CAH and FMPP, growing children are seen twice a year, and adults and children who have reached adult height may be seen annually. Additional visits may be scheduled if medically indicated. In this part of the study, females are asked to keep a record of their periods after their first menstrual cycle.

This observational natural history study will follow individuals with MEHMO (Mental disability, Epileptic seizure, Hypopituitarism/Hypogenitalism, Microcephaly, Obesity) syndrome or an eIF2-pathway related disorder, who have symptoms such as intellectual delay, seizures, abnormal hormone and blood sugar levels, and decreased motor skills. No current treatment for these conditions is available. A major impediment to the testing of potential therapeutic interventions is the lack of well-defined outcome measures. This protocol seeks to identify biochemical and clinical markers to monitor disease progression, and better understand the natural history of these conditions. Any person diagnosed with MEHMO syndrome or related conditions, who can travel to the NIH Clinical Center can participate in this study. The study involves: * General health assessment and evaluation * Imaging studies * Laboratory tests * Collection of blood, urine, spinal fluid, skin biopsy.

Background: The lymphatic system is a network of vessels that carry a clear fluid called lymph through the body. Problems in the lymphatic system can cause pain, fluid buildup, and issues with immunity. There is much researchers do not understand about lymphatic anomalies. In this natural history study, they will collect data from a lot of people over a long time. Objective: To better understand why lymphatic anomalies develop. The goal is to improve future treatments. Eligibility: People aged 0 days and older with a suspected or confirmed lymphatic anomaly. Their unaffected parents or siblings aged 7 years or older are also needed. Design: Participants may remain in the study indefinitely. Affected participants may be evaluated every 10 months to 2 years. Some participants will be seen over telemedicine. Others will be seen at the NIH Clinical Center for 2-5 days. All participants will have a physical exam. They may provide specimens including blood, saliva, hair follicles, stool, skin, and other tissues. Samples may be used for genetic testing. Participants may undergo other tests depending on their medical conditions. The NIH Clinical Center visit may include: Heart tests include placing stickers on the chest to measure electrical activity and using sound waves to capture pictures of the heart. A lung test measures the muscle strength in the chest. Participants will blow into a tube. Photographs may be taken of participants faces and other features. Imaging scans will take pictures of the inside of the body. One scan will measure bone density. One type of scan tracks how lymph fluid moves through the body. Participants will be under anesthesia, and they will be injected with a dye.

Background: Turner Syndrome, galactosemia, and premature ovarian insufficiency are all conditions that may make it very hard or impossible for a person to become pregnant and have their own child. Researchers want to learn more about why this happens and if freezing Gonadal tissue allows for fertility preservation. Objective: To find out why people with certain conditions have can have premature ovarian insufficiency (POI or early menopause) and individuals with variations in sex characteristics have trouble getting pregnant and if freezing the gonads tissue from them will help to have their own child in the future. Eligibility: Individuals aged 2-21 who have Turner Syndrome or galactosemia. Also, females aged 13-21 with premature ovarian insufficiency, individuals with variations in sex characteristics, and individuals 2-35 receiving high-risk gonadotoxic therapy Design: Participants will be screened with a medical history. Participants may have a physical exam and blood tests. Their body measurements may be taken. These include weight, height, arm span, skin fold, and sitting height. They may fill out surveys about their quality of life, body image, and health. Participants may have a transabdominal pelvic ultrasound. A probe will be placed on their belly and will take pictures of the organs in the pelvis. They may have a transvaginal pelvic ultrasound performed while asleep in the operating room if needed. Participants may have surgery to remove an gonads and skin biopsy. The removed tissue will be frozen and stored. The tissue will have to be stored for many years. NIH will pay to store the tissue for 1 year. After that, participants will have to pay for storage. A piece of the gonads (no more than 20%) will be used for research Travel, lodging and meals for participants traveling greater than 50 miles will be reimbursed based off the government rate. Local participants will not be reimbursed. Participants will have a checkup 6 weeks after surgery one or more follow-up visits 6-18 months after surgery. They may have phone follow-up every 12-24 months after surgery. Participation will last 30 years.

Background: Androgen effects in humans are usually (but not always) mediated by the androgen receptor which is coded for by the androgen receptor gene (AR gene). Androgen Insensitivity Syndrome (AIS) is a rare condition in which the body cannot sense the male hormones in the blood or tissue. Both women and men can be affected by AIS. Researchers want to learn more about the health of people with AIS over time. With a natural history study in individuals with AIS, data and tests may provide information regarding health risks (including the risks and benefits of gonadectomy and best ways to monitor for tumor) and optimal management of individuals with AIS as well as elucidate the role of the androgen receptor in human health. This study does not involve any interventions and we can provide clinical care while collecting data. Objective: The objective of this natural history study is to describe and define a comprehensive phenotype (characteristic) of patients with AIS based on confirmed androgen receptor (AR) gene difference. We will evaluate hormones, bone density and markers, cardiovascular and metabolic parameters, as well as quality of life and tumor formation risk and evaluation. The purpose is to obtain a better understanding of the overall health issues that people with AIS may have through the study procedures listed. Eligibility: People ages 8-99 with AIS and their adult relatives Design: Participants will go through a series of study procedures for data and specimen collection. This will be done to understand how AIS affects individuals since the androgen receptor is found in many tissues in the body including skin, bone, muscle, and the neurologic, immune and metabolic systems. All tests will be performed by skilled and trained study professionals. Participants will be screened with: Medical history Physical exam Medical record review Lab tests. Participants will have physical exams. Their body measurements will be taken. They will have blood and urine tests. They will have electrocardiograms to check heart health. They may complete questionnaires. They may have an Oral Glucose Tolerance Test. Participants may have x-rays and HRpQCT scans taken of the hand, wrist, and other bones. Participants will have body scans to measure bone thickness. Participants will have magnetic resonance imaging (MRI) or sonogram of the pelvis. For MRI, they may get a contrast agent via intravenous (IV) catheter. Adult participants may have the following: MR elastography. It uses MRI and low-frequency vibrations to map stiffness of body tissues. MR spectroscopy. It uses MRI to take pictures of chemicals in the liver and body fat. Cardiac computed tomography scan. It uses x-rays to make pictures of the heart. Participants may get a contrast agent via IV. Optional genital exam. Optional one-time vaginal swab. Participants will have visits every 1-2 years. Participation lasts indefinitely. Adult relatives will also be invited to participate but will have only 1 visit. It will include some of the above tests.

Background: Endocrine glands give off hormones. Researchers want to learn more about the disorders that affect these glands in children. These disorders might be caused by changes in genes. Genes contain DNA, which is the blueprint of how a cell works. Researchers want to identify the genes involved in endocrine and metabolic disorders. This might help develop new ways to diagnose and treat the disorders. Objective: To study the inheritance of endocrine or metabolism disorders. Eligibility: Children ages 3month-18 with known or suspected endocrine or metabolism disorders. Family members ages 3months-100. They may participate in the DNA part of the study. Design: Participants will be screened with a review of their medical records. Their parents or guardians will allow the records to be released. Participants will have a clinic visit. This may include a physical exam and medical history. Parents or guardians will give their consent for the study. Participants may have tests, surgery, or other procedures to help diagnose or treat their condition. These could include: Blood, urine, and saliva tests Growth hormone test Pituitary and adrenal function tests Picture of chromosomes Imaging tests. These may include X-ray, ultrasound, scans, or a skeletal survey. Genetic tests Sleep study Medical photographs If surgery is done, a tissue sample will be taken. Participants may have follow-up visits for diagnosis and treatment. Participating relatives will have one visit. This will include medical history and blood and saliva tests. The blood and saliva will be used for DNA testing.

Background: Medical advances have improved survival rates for many cancers and other illnesses. This means that more people are coping with the long-term effects of these treatments. Some treatments can cause female infertility. Ovarian tissue cryopreservation (OTC) may help. Before undergoing a treatment that may damage their fertility, patients may opt to freeze a sample of ovarian tissue. The tissue contains immature egg cells. When thawed, the tissue can be reimplanted. This procedure can help women become pregnant. Objective: This natural history study will create a databank of ovarian tissue. The NIH will provide OTC as a clinical service. The NIH will also request a portion of the tissue to use for research. Eligibility: Females aged 4 to 35 who opt to have OTC before receiving cancer treatment. Design: Participants will be screened. Their existing medical records will be reviewed. They will be asked if they want to donate a portion of their ovarian tissue for research. No more than 20% of the tissue collected will be taken for research. Some other tissues that would otherwise be discarded will also be kept. Medical data from each participant may also be collected and stored in the database. This data may include results of routine blood tests, imaging tests, and other information. The data will be coded for privacy. Participants will answer a questionnaire. They will be asked about their fertility treatment and general health. The survey takes about 30 minutes. They will repeat the questionnaire once a year for 30 years.

Background: There are 461 conditions that affect the bones (skeletal disorders). Many of these are not well understood and do not have any specific treatments. Researchers want to collect more data about these conditions. Objective: To gain more information about the causes of skeletal disorders and how they progress over time. Eligibility: People ages 2 months or older with known or suspected skeletal disorders or history of pregnancy affected by skeletal findings. Also, healthy family members of affected enrolled participants. Design: Participants can take part in the study either remotely or in person. Those who take part remotely may send in medical records, blood samples, photographs, and other materials. Participants medical records will be reviewed. They may give blood and/or urine samples. They will give blood, saliva, or tissue samples for genetic tests. They may have genetic counseling. Participants ages 2 years and older may have different kinds of imaging scans, such as x-rays. For these scans, they may have to lie still while machines take pictures of their bones. Participants with skeletal disorders who come to the clinic will be examined. They may be asked to stay in the hospital for a few days to take extra tests. They may have a bone or skin biopsy. Participants with skeletal disorders may be photographed to show the effects of their disorder and how it changes over time. For participants with skeletal disorders, their blood or tissue samples may be used to make a special type of stem cell. These cells can be used in the laboratory to make many other types of cells. A large supply of these cells may be created for research. Participation will last indefinitely.

Background: Obstructive sleep apnea (OSA) occurs when the blockage of the airway causes a person to stop breathing involuntarily for 10 seconds or more throughout the night during sleep. Pediatric OSA can be especially concerning and can have long-term effects. Researchers want to see how a monitoring device called near-infrared spectroscopy (NIRS) compares with the traditional techniques used in children s sleep studies. Objective: To learn about oxygen levels in the brain and limbs in children with and without sleep apnea using a wearable, point-of-care biosensor. Eligibility: Children aged 3-12 who have OSA and plan to receive treatment (OSA group) or who do not have OSA (NORM group). Design: Participants will be screened with a review of their medical records. If they have taken part in other NIH studies, that data will be reviewed as well. Participants in the NORM group will have 1 overnight study visit. Those in the OSA group will have 2 overnight study visits. Participants will do an overnight sleep study. They will have a physical exam and medical history. They will have a sleep study electroencephalography (EEG). For this, electrodes will be placed on their head. They will wear a gauze cap to keep the electrodes in place. Two NIRS probes made of a soft silicon will be placed on their forehead and arm. They will follow their normal bedtime routine. Their parent will stay overnight. The OSA group will have a second study visit 2 weeks to 12 months after they start treatment for their sleep apnea. They will repeat the sleep study.

There is a variety of tumors affecting the pituitary gland in childhood; some of these tumors (eg craniopharyngioma) are included among the most common central nervous system tumors in childhood. The gene(s) involved in the pathogenesis of these tumors are largely not known; their possible association with other developmental defects or inheritance pattern(s) has not been investigated. The present study serves as a (i) screening/training, and, (ii) a research protocol. As a screening and training study, this protocol allows our Institute to admit children with tumors of the hypothalamic-pituitary unit to the pediatric endocrine clinics and wards of the NIH Clinical Center for the purposes of (i) training our fellows and students in the identification of genetic defects associated with pituitary tumor formation, and (ii) teaching our fellows and students the recognition, management and complications of pituitary tumors As a research study, this protocol aims at (i) developing new clinical studies for the recognition and therapy of pituitary tumors; as an example, two new studies have emerged within the context of this protocol: (a) investigation of a new research magnetic resonance imaging (MRI) tool and its usefulness in the identification of pituitary tumors, and (b) investigation of the psychological effects of cortisol secretion in pediatric patients with Cushing disease. Continuation of this protocol will eventually lead to new, separate protocols that will address all aspects of diagnosis of pituitary tumors and their therapy in childhood. (ii) Identifying the genetic components of pituitary oncogenesis; those will be investigated by (a) studying the inheritance pattern of pituitary tumors in childhood and their possible association with other conditions in the families of the patients, and (ii) collecting tumor tissues and examining their molecular genetics. As with the clinical studies, the present protocol may help generate ideas for future studies on the treatment and clinical follow up of pediatric patients with tumors of the pituitary gland and, thus, lead to the development of better therapeutic regimens for these neoplasms.

Background: Niemann-Pick type C (NPC) disease is a rare, progressive neurodegenerative disease that affects mainly the brain, liver, and spleen but also other parts of the body. There is no cure for NPC, and symptoms only get worse over time. Symptoms can include seizures, difficulty moving or talking, or dementia. But symptoms can vary among different people with the disease. Some may have seizures, while others do not, for example. Some people begin showing symptoms in childhood; in others, symptoms may not appear until they are adults. Researchers want to learn more about why NPC affects people differently. This natural history study will gather data from people with NPC in order to understand more about the disease and how it affects the body. Objective: This study will create the first and largest database about NPC. Eligibility: People of any age who have NPC. Design: Participants will have blood drawn from a vein. This will happen only once. The blood will be used to analyze the participants DNA. The participants medical records will be reviewed. The study team will collect data on participants NPC diagnosis and symptoms; they will record how long participants have had each symptom. The study team will also collect data on each participants age, sex, race, height, weight, medications, and other test results. The study team will communicate with participants. They will discuss the study and answer any questions. Participants will receive up to $190.

The goal of this study is to develop better methods of diagnosis, localization, and treatment for pheochromocytomas. These tumors, which usually arise from the adrenal glands, are often difficult to detect with current methods. Pheochromocytomas release chemicals called catecholamines, causing high blood pressure. Undetected, the tumors can lead to severe medical consequences, including stroke, heart attack and sudden death, in situations that would normally pose little or no risk, such as surgery, general anesthesia or childbirth. Patients with pheochromocytoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Study participants will undergo blood, urine, and imaging tests, described below, to detect pheochromocytoma. If a tumor is found, the patient will be offered surgery. If surgery is not feasible (for example, if there are multiple tumors that cannot be removed), evaluations will continue in follow-up visits. If the tumor cannot be found, the patient will be offered medical treatment and efforts to detect the tumor will continue. Main diagnostic and research tests may include the following: 1. Blood tests - mainly measurements of plasma or urine catecholamines and metanephrines as well as methoxytyramine. If necessary the clonidine suppression test can be carried out. 2. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 123I-MIBG scintigraphy and FDG (positron emission tomography) PET/CT. These scans may be done before and/or after surgical removal of pheochromocytoma. 3. Research PET scanning is done using an injection of radioactive compounds. Patients may undergo 18F-FDOPA, 18F-DA, as well as 68Ga-DOTATATE PET/CT . Each scan takes up to about 2 hours. 4. Genetic testing - A small blood sample is collected for DNA analysis and other analyses.

Background: The pituitary gland produces hormones. A tumor in this gland can cause it to produce too much of the hormone cortisol. Too much cortisol in the body causes Cushing disease. This disease causes many problems. Some of these problems might persist after the disease is cured. Objective: To find out the long-term effects of exposure to high levels of cortisol during childhood and adolescence. Eligibility: People ages 10-42years who were diagnosed with Cushing disease before age 21 and are now cured and have normal or low cortisol levels People related to someone with Cushing disease Design: Participants will be screened with a medical history. Participants will complete an online survey. This will include questions about their or their child s physical and mental health. All participants will be seen at 5 -year intervals after cure of Cushing disease (5yr, 10yr, 15yr, 20yr (last visit)) Participants who have a relative with Cushing disease will have a medical history and blood tests or cheek swabs. Participants who have the disease will have: Physical exam Blood tests Cheek swab DXA scan: A machine will x-ray the participant s body to measure bone mineral content. For participants who are still growing, a hand x-ray Participants with the disease may also have: Hormone stimulation test: Participants will get a hormone or another substance that will be measured. Serial hormone sampling: Participants blood will be measured several times through a thin plastic tube in an arm vein. Urine tests: Participants urine may be collected over 24 hours. MRI: Participants may have a dye injected into a vein. They will lie on a table that slides into a machine. The machine will take pictures of the body.

Background: Ollier disease (OD) and Maffucci syndrome (MS) are rare disorders that increase the risk of cancers in cartilage tissue. These tumors can lead to severe skeletal deformities beginning in childhood. People with OD or MS are also at an increased risk of blood vessel disorders and specific cancers. Researchers want to learn more about what causes these disorders. Objective: To understand the genetic causes of OD and MS. Eligibility: People aged 2 years and older who have OD or MS with cartilage tumors or blood vessel disorders. Design: Participants will stay at the NIH clinic for 5 days. They will undergo these procedures: A physical exam with blood tests. DXA (dual-energy X-ray absorptiometry) scan. The DXA scan measures the density of bones. Participants will lie on a table while a machine uses low-level X-rays to scan their body. MRI (magnetic resonance imaging) scan. An MRI uses strong magnets to take pictures of the tissues inside the body. Participants will lie on a table that slides into a large tube. A contrast dye may be injected through a needle inserted into a vein in the arm. X-rays. Some participants may have full-body X-rays instead of an MRI. X-rays take pictures of bones and other internal tissues and organs, such as the heart, lungs, and airways. PET (positron emission tomography) and CT (computed tomography) scans. Adult participants will have 2 other scans. The PET scan will include a radioactive injection into a vein. They will also have a full-body CT scan.

Background: Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder. It can cause birth defects and developmental delays. There is no cure for SLOS or other inherited diseases related to cholesterol production or storage. The data gained in this study may help researchers find ways to measure how well future treatments work. Objective: To learn more about SLOS and related disorders and how these diseases affect participants and relatives. Eligibility: People of any age who have or are suspected to have SLOS or another inherited disease related to cholesterol production or storage. Relatives are also needed. Design: Participants will be screened with a medical record review. Participants will have visits every 6 to 12 months. They will have a physical exam. They will fill out a survey about their medical and behavioral history. They may have an eye exam. They may have a neurodevelopmental assessment. They may have a hearing test. Their outer and middle ears may be examined. Their ability to speak, understand speech, eat, and swallow may be assessed. They may get X-rays while they chew and swallow. Their functional ability and needs for adaptive devices or braces may be assessed. They may have a lumbar puncture. Photographs may be taken of their face and body. Participants who cannot visit the NIH and relatives will have a virtual visit once a year. They will talk about their medical history and symptoms. They give blood, urine, and skin samples at a lab near their home. They will fill out a survey about their medical and behavioral history. Participation will last for several years.

Background: Creatine transporter deficiency (CTD) is a genetic disorder that mainly affects the brain in males. CTD causes intellectual disability that can be mild to severe. People with CTD may have seizures and behavioral issues. They may have slow growth and tire easily. CTD may sometimes be confused with autism or other disorders. Better diagnostics are needed. The study team in an NIH study noted that the faces of children with CTD can look similar. For this natural history study, an expert will examine photos of children with CTD. Any shared traits found might help to diagnose CTD. Objective: To look for shared facial features of children with CTD. Eligibility: Males aged 2 to 40 years old with CTD who were in study 17-CH-0020. Design: Some participants in study 17-CH-0020 had pictures taken of their faces. The NIH study team wants to share these photos with a colleague in Canada. This person is an expert at evaluating how genetic disorders affect people s bodies. Participant data collected during the study may also be sent to this expert. This data may include diagnostic images and results from lab tests. Some children did not have their pictures taken during study 17-CH-0020. Parents are asked to take pictures of these children and send them to the study team. These photos can be sent to a secure portal. The photos can also be taken in-person during a clinic visit. The photos may be printed in clinical study journals. But this is not required. Parents will be asked to sign a separate consent before the photos are published....

Background: People show changes in brain activity when they watch other people do actions. This may be part of early social and communication skills. Researchers want to understand the stages of normal development of motor observation and imitation in people and how it relates to social development in infants and toddlers. Objective: To study the nature of brain activity that underlies typical brain functioning in infants, toddlers, and adults. Eligibility: Infants ages 8 12 months Healthy adults ages 18 65 Design: Adult participants will have one visit. They will: Answer questions about their family, like its size and ethnicity. Answer questions about their own behavior and do a simple motor task. Have EEG/fNIRS. A damp elastic cap with small sensors will be placed on the head. Participants will observe stimuli, either on a video screen or of a live person. The sensors will be connected to a computer. That will record the participant s brain activity while watching pictures on a screen. Infant participants will have 2 visits. Their parents will answer questions about their family. The parents will fill out forms about their child s development. These will be mailed to them before each visit. Parents will stay with their infant while study staff does an assessment of the child s communication, motor, and thinking skills. Infants will have EEG/fNIRS. Infants who are at risk for developmental delays will come back for another visit when they are about 2 years old. This will repeat the infant visits but it will not include EEG/fNIRS. Some questionnaires and assessments will be videotaped.

Background: Turner syndrome (TS) is a rare genetic condition. It happens when a person is born missing all or part of an X sex chromosome. People with TS can have heart defects, short stature, autoimmune conditions, and malformations. Many women with TS never have periods and cannot conceive; however, some women have normal ovaries (egg cells). Researchers want to learn more about why some women with TS are fertile and others are not. To do this, they need to be able to compare the genes of many women who have TS. Objective: To create a genetic database of people with TS. Eligibility: People of any age with TS. Biological parents and other relatives are also needed. Design: Participants who agree to join this study will be asked to enroll in a second study; that study is called NIAID Centralized Sequencing Protocol (Protocol No. 17I0122). Participants will have 1 study visit. They may fill out a survey or do an interview. They will provide blood, saliva, or other tissue samples. Those samples will be used for genetic tests. The visit will take 1 hour. The information collected in those tests will be collected for use in the database created as part of this study.

Background: Gynecologic conditions are those that are related to the reproductive system. They can be reproductive gland disorders or reproductive system tumors. They can also be inborn anomalies of the reproductive tract. Researchers want to gather data over time from a large group of young people with these conditions. Objective: To create a database about child and teenage gynecologic conditions. Eligibility: Participants of any age with known or suspected pediatric and adolescent gynecologic conditions, and their adult family members Design: Participants will be screened with a review of their medical records. Participants may have a medical history and physical exam. Participants will have blood drawn using a needle. The blood will be used for genetic tests. Participants will have saliva collected. They will spit into a small plastic container. Or their spit will be absorbed from their mouth using a small sponge. The saliva will be used for genetic tests. Participants may have samples collected from their vagina. A small cotton swab will be used to gather the samples. This procedure is optional. If participants have a surgery related to their condition, a small tissue sample will be taken. It will be stored for future research. Participants may complete optional surveys. These surveys ask about their physical and emotional health. They can choose not to answer any of the questions. Researchers will collect medical data from participants standard tests. Such tests may include blood and urine tests, X-rays, nuclear medicine scans, and other tests. Data will also be collected from standard treatments they may receive.

Background: Infertility affects 1 in 6 people. Often, the causes of infertility are unknown. Treatments are successful in only about 50% of cases. Infertility caused by non obstructive azoospermia in males and primary ovarian insufficiency in females can have genetic causes. Researchers want to learn more about these genes. Objective: To identify genes that may cause infertility. Eligibility: Adult men and women with non-obstructive azoospermia (NOA) or primary ovarian insufficiency (POI) of unknown cause. Design: Participants will provide a saliva sample. A kit will be sent to their home. The kit will contain a collection tube and a cotton swab. They will swirl the swab inside their mouth and then seal it in the tube. They will mail the tube back to the researchers. Male participants who are having a procedure done to collect tissue from their testes may opt to have leftover tissue provided to study researchers. This tissue would otherwise have been discarded. No new procedures will be performed just for this study. Data may be collected from participants medical records.

Background: CLN3, or Batten disease, is a genetic disorder. This deadly disease leads to decline of brain and nervous system functions. Symptoms of CLN3 typically occur between 4 and 7 years of age. They include changes in how a person sees, thinks, and moves. CLN3 can also cause seizures. No effective treatments for the disease are yet known. There is limited testing of potential therapies. Researchers want to study CLN3 more so they can improve future therapies. Objective: To identify clinical or biochemical markers that can be used as therapeutic outcome measures for CLN3. Eligibility: People with CLN3. It must be based on Two CLN3 mutations OR One CLN3 mutation AND findings seen with a powerful microscope Family members of a person with CLN3. Design: Participants will have already been referred to NIH for CLN3 evaluation. If participants agree to do the study, they will: 1. give spinal fluid, blood, urine, and skin samples. They may provide other samples if they were already collected. These may include cells, surgical specimens, and DNA. 2. will be seen by multiple healthcare specialists. Participants may provide medical records or photos. Participants will sign a release of medical records form.P Researchers may send samples or clinical data to other investigators. For research testing, the samples will not include the participant s name. For a test in a clinical lab, researchers will include the participant s name. These results will become part of the clinical record at NIH.