Trial record 1 of 5 for:    "Holoprosencephaly"
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Clinical and Genetic Studies on Holoprosencephaly

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: July 23, 2004
Last updated: June 25, 2014
Last verified: May 2014

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.


Study Type: Observational
Official Title: Clinical and Genetic Studies on Holoprosencephaly

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 250
Study Start Date: January 2004
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.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

    1. Depending on their willingness to participate, subjects may enroll in DNA laboratory-only (98-HG-0249), psychosocial-only, or clinical-only. However, to conserve resources and meet study objectives, subjects with known mutations will be given priority in selection for extensive clinical studies. All races and genders are known to be at risk for HPE, anywhere in the world. Nationality or place of origin is not specific barrier to participation.
    2. Direct blood relatives (typically parents, and occasionally siblings of affected individuals) of patients with HPE are also eligible to participate.
    3. Individuals with fatty livers (or related hepatic changes such as steatohepatitis), but without HPE, may participate by submitting a blood sample for DNA testing.


  1. Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.
  2. Medical condition(s) or mental retardation are not in themselves reason for exclusion if in the judgment of the referring physician this would involve no more than minimal risk. We anticipate that children with mental handicaps would be included in the research population. We will make every effort to explain the study for the purpose of assent in a manner that the family feels is both age and developmentally appropriate for that child.
  3. We generally review a brief clinical description from the referring physician about a potential research subject to determine that the subject is appropriate to enter into the study. We reserve the right to exclude cases that are clearly not HPE or related to our direct research interests (e.g. HPE cases that are syndromic like Smith Lemli Opitz syndrome, Trisomy 13, Trisomy 18, drug-related, or teratogen-related). This almost never happens, and we would attempt to make referrals to a more appropriate investigator.
  4. Similar to above, in regards to individuals with fatty livers (or related hepatic changes such as steatohepatitis or fibrosis), we will review a brief clinical description from the referring physician to determine that the subject is appropriate to enter into the study. We reserve the right to exclude participants who have liver abnormalities for reasons not directly related to our direct research interests (such as chronic alcohol use or infectious causes). However, as some of these environmental factors may contribute to a multifactorial etiology of hepatic changes, we may not exclude all such cases.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00088426

Contact: Benjamin D Solomon, M.D. (301) 402-8167
Contact: Maximilian Muenke, M.D. (301) 402-8167

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
Principal Investigator: Maximilian Muenke, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications: Identifier: NCT00088426     History of Changes
Other Study ID Numbers: 040093, 04-HG-0093
Study First Received: July 23, 2004
Last Updated: June 25, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Additional relevant MeSH terms:
Abnormalities, Multiple
Agenesis of Corpus Callosum
Chromosome Disorders
Congenital Abnormalities
Craniofacial Abnormalities
Genetic Diseases, Inborn
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Nervous System Diseases
Nervous System Malformations processed this record on October 21, 2014