Clinical and Genetic Studies on Holoprosencephaly

Brain Disorders Clinical Trial

Official title: Clinical and Genetic Studies on Holoprosencephaly

Status Completed

Clinical Trial 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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Clinical Trial 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. ;

Related Conditions & MeSH terms

• Brain Diseases
• Brain Disorders
• Developmental Delay Disorders
• Developmental Disabilities
• Disease
• Holoprosencephaly
• HPE

• NCT number: NCT00088426
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Start date: January 23, 2004
• Completion date: April 16, 2020