View clinical trials related to Holoprosencephaly.
Filter by:Holoprosencephaly, or HPE, is the most common congenital cerebral malformation in humans and the most severe of a group of pathologies related to a deficiency of the SHH signalling pathway (Sonic Hedgehog SHH-D). It is characterized by severe cerebral and craniofacial abnormalities. The regulation of SHH concentration is therefore crucial for correct craniofacial development. Despite the recent identification of about 20 genes, 70% of cases of EHPE and craniofacial midline abnormalities of genetic origin do not have a molecular diagnosis. It is therefore important to continue the search for new candidate genes to improve the understanding of brain and facial development and to improve genetic counseling for these families. The development of Next-Generation Sequencing (NGS) technologies opens up the possibility of studying the exome or even the genome in a single manipulation. The latter type of analysis is particularly well suited to the discovery of new genes and will therefore improve the care of patients and their families.
A study of the complex genetics of brain development will be undertaken with an emphasis on those genes that cause the most common structural brain anomaly in humans called holoprosencephaly (HPE). This malformation of the brain can result from either environmental or genetic causes, and it is the aim of these investigations to determine the genes responsible for both normal and abnormal brain development through the study of patients with this disorder. Mutations in one such gene, Sonic Hedgehog, have been shown by us to be responsible for approximately one quarter of familial cases of HPE. Other genes either related to the hedgehog pathway or located at unrelated defined genetic loci may also contribute to HPE and are the subject of active investigation. We anticipate that many genes important for normal brain development will be identified in the search for genetic causes of HPE.
This study will examine how holoprosencephaly (HPE) affects people, how they change over time, and what genes may be involved in the cause of the disorder. HPE is a defect of brain development in utero in which the forebrain fails to sufficiently divide into two hemispheres, resulting in a single-lobed brain and skull and facial malformations. In most cases, the defects are so severe that babies die before birth. There are three classifications of HPE. In alobar HPE the brain does not divide at all; this form is usually associated with severe facial deformities. In semilobar HPE the hemispheres divide somewhat, causing an intermediate form of the disorder. In lobar HPE, the mildest form, separation of hemispheres is nearly normal. Patients with HPE and their direct blood relatives may participate in this study. Patients are seen by a team of medical specialists at the NIH Clinical Center for the following procedures: - Physical and neurological examination - Eye examination - Imaging studies, such as echocardiogram, abdominal ultrasound, brain MRI - Electroencephalogram (EEG) - Hearing evaluation - Blood and urine samples for genetic and endocrine studies, routine blood chemistries, urinalysis, and urine electrolytes - Other consultations as needed - Possibly photographs, including front and side views of the face and other body parts that may be involved in HPE, such as the eyes, teeth, hands, and feet Parents will be asked questions about the child's prenatal, birth, newborn, and past medical history, growth, behavior and development, and therapy and medication. Because HPE is a genetic disorder and gene changes can be passed on in a family, parents will also be asked to undergo the following procedures: - Completion of a medical and family history form - Physical and neurological examination - Blood and urine samples (for mothers only) - Specialty consultations as indicated - Possibly photographs, including front and side views of the face and other body parts that may be involved in HPE, such as the eyes, teeth, hands, and feet - Psychosocial study. Some parents will be asked to participate in a telephone interview or complete a questionnaire, or both, about their attitudes, beliefs, and concerns about how they and their family cope with their child's condition. Some questionnaires may include questions about aspects of their marriage and personal feelings and experiences. Parents will meet with a doctor and a genetics nurse to discuss the results of the tests and answer questions. Parents may be asked to bring their child back to the NIH after 2 years for follow-up examination and possible additional or repeat testing. ...
This study will examine the experiences of parents who decided to continue a pregnancy after receiving a prenatal diagnosis of holopresencephaly (HPE). HPE results from a genetic defect that can cause facial abnormalities such as cleft lip and cleft palate, learning disabilities, muscle weakness, problems with digestion, sleep and muscle control, and other disabilities. The severity of symptoms varies greatly among affected children. Parents whose child was diagnosed before birth with HPE may be eligible for this study. It involves a one-time interview that takes from about 45 to 60 minutes. The interview is conducted either in person or by telephone and consists of three parts, as follows: 1. The experience of receiving the diagnosis of HPE during the pregnancy < includes general questions such as when and how HPE was diagnosed, what kind of information the parent received, the parent's reaction to the diagnosis, what genetic counseling, if any, the parents received, and so forth. 2. Emotional and informational needs < includes questions about the parent's specific emotional and informational needs from the time of diagnosis until the baby's birth, and the parent's reactions to support that was given. 3. Questionnaire < includes questions about the parent and his or her child, such as the parent's age, gender, marital status, and religious background, the child's age, gender, medical problems, and so forth. The questionnaire will be completed verbally for telephone interviews and in writing for in-person interviews. The interview will be tape-recorded and will be kept confidential. Information from this study will provide health professionals, including genetic counselors, more effective strategies for helping other parents who face similar prenatal diagnoses.