Clinical and Genetic Studies on Holoprosencephaly
- Conditions
- HPEDevelopmental Delay DisordersHoloprosencephalyBrain Disorders
- Registration Number
- NCT00088426
- Lead Sponsor
- National Human Genome Research Institute (NHGRI)
- Brief Summary
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.
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- Detailed Description
Holoprosencephaly (HPE) is a defect of midline forebrain development that occurs soon after conception. It has a prevalence of 1 in 250 during early embryonic development, and 1 in 10,000 to 1 in 20,000 at term. In live born infants, the abnormalities associated with HPE are divided into three main categories: alobar, semilobar, and lobar HPE. A fourth variant, middle interhemispheric variant, has also been recognized. The purpose of this study is to increase our understanding of the genetic and clinical manifestations of HPE through detailed physical, psychological, developmental, neurologic, endocrinologic, and radiologic studies. We will examine the spectrum of clinical characteristics of HPE to facilitate early diagnosis and clinical management, including genetic counseling. Finally, we plan to assess the psychosocial impact of HPE on the family as a unit. Most patients and their families will be seen at the NIH Clinical Center. A subset may be examined outside the NIH, and a further subset, for the psychosocial studies, may be interviewed by phone.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 256
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the psychosocial impact of HPE on the family system. Once with possible followup at Year 2 (a) To describe characteristics of stress and coping in families of children affected by HPE. (b) To examine the relationships between specific child characteristics (e.g., chronological age, severity of disorder), family coping styles and family variables (e.g., stress, coping, marital satisfaction, parental anxiety and depression).(c) To examine the similarities and/or differences between mothers and fathers experiences of stress and coping in families of children with HPE. (d) To generate data for the development of a new instrument to quantify stress, coping and resilience in HPE families.
To determine the spectrum of non-neurologic anomalies resulting from mutations in HPE-associated genes /pathways both in individuals with HPE and individuals without HPE. Once with possible followup at Year 2 (a) To determine the association between mutations in HPE-associated genes/pathways and the non- neurologic finding of fatty liver in individuals with HPE. (b) To determine the presence of other, previously unknown clinical manifestations in individuals with HPE.
To characterize the physical, developmental, neurologic, endocrinologic and radiologic phenotype of HPE through this comprehensive natural history study. Once with possible followup at Year 2 To characterize the physical, developmental, neurologic, endocrinologic and radiologic phenotype of HPE through this comprehensive natural history study.
To examine the spectrum of clinical characteristics of HPE and facilitate early clinical recognition, diagnostic confirmation, anticipatory management, prognostication, and proper genetic counseling. Once with possible followup at Year 2 (a) To compare gene mutations (with known or suspected abnormal functional effects) with the phenotypes observed in patients (i.e genotype-phenotype correlations) as documented in the study. (b) To determine the spectrum of brain malformations caused by genetic changes in HPE candidate genes that are known or suspected to cause human disease. (c) To correlate neurodevelopmental status/clinical outcome with neuroradiologic findings and genetic changes in HPE candidate genes. (d) To verify recurrence risks /inheritance patterns of HPE for each of the HPE candidate genes.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States