Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System

Summary: Background:
  - Researchers are interested in studying individuals who have known or suspected metabolic or genetic diseases that put them at a high risk for heart diseases or diseases of their blood vessels. To improve the results of the study, both affected and nonaffected individuals will be asked to provide blood and other samples and will undergo tests to evaluate heart and lung function. Nonaffected individuals will include relatives of affected individuals and healthy nonrelated volunteers.
  Objectives:
  - To study individuals who have or are at risk for cardiovascular diseases, as well as their unaffected relatives and healthy volunteers.
  Eligibility:
  - Individuals between 2 and 100 years of age. Participants may be healthy volunteers, individuals with cardiovascular diseases, or unaffected relatives of individuals with cardiovascular diseases.
  Design:
  -  Participants will have some or all of the following tests, as directed by the study researchers:
  -  Photography of the face and full body
  -  Body measurements
  -  Radiography, including chest or limb x-rays
  -  Metabolic stress testing to study heart and muscle function
  -  Echocardiography to study heart function
  -  Magnetic resonance imaging (MRI) studies, including cardiovascular MRI, angiography, and contrast MRI, to study heart function and performance
  -  Computed tomography (CT) angiogram to obtain images of the heart and lungs
  -  Positron emission tomography (PET) imaging to study possible fat infiltration of the heart
  -  Six-minute walk test to study heart, lung, and muscle function and performance
  -  Vascular ultrasound to study blood vessel walls
  -  Blood, tissue, and other specimens will be collected for research and testing, and will be taken either as part of the clinical study or during surgical procedures.
  -  Follow-up studies may be performed under separate research protocols.

Detailed description: We propose to characterize the etiology and natural history of rare and uncommon diseases, both known and unknown that present with symptoms and signs associated with the risk of overt or potential cardiovascular dysfunction. We will also study rare genetic modifiers and identify novel disease mechanisms contributing to common cardiovascular diseases. In so doing, we will expand our knowledge about these disorders and provide access to subjects interest for research, teaching, and clinical experience. Individual subjects seen under this protocol may initiate the establishment of specific disease-related protocols involving intensive natural history studies, disease discovery and potential innovative therapeutic studies. In addition to its role in investigating individuals who are of interest to the Center for Molecular Medicine (CMM) and the Cardiovascular and Pulmonary Branch (CPB) of the NHLBI, this protocol can provide a possible avenue for admitting subjects from other NIH programs such as the NIH Undiagnosed Diseases Program, the Center for Human Immunology Trans-institute program or other NIH protocols where subjects exhibit cardiovascular features.

Eligibility: -  INCLUSION CRITERIA:
  Eligible subjects may include anyone over 2 years of age who is affected with diseases/disorders (index cases), or who is a relative of a person who is affected with diseases/disorders.
  -  Pregnant women are eligible to participate in this study if they have been referred with a known or suspected pathology, if they are a relative of an index case with a known or suspected pathology, or if they are healthy volunteers.
  -  Healthy adult volunteers must be 18 years of age or older, and must agree to have blood or tissue samples studied, and potentially stored for future research.
  -  Index case subjects enrolled in this protocol will have been referred with a known or suspected pathology that may be associated with cardiovascular dysfunction or risk with a suspected atypical presentation, heritable disorder, or genetic predisposition. The investigator with expertise in the presentation of the subject, along with consulting specialists, will review the medical records of prospective subjects and offer admission based upon the potential to help the individual, to learn from the subject, or to initiate clinical or basic research suggested by the subject s workup.
  EXCLUSION CRITERIA:
  -  Persons of less than 2 years of age or greater than 100 years of age
  -  Healthy volunteers unable to give informed consent or who decline to have blood and/or tissue studies, or who do not consent to have samples stored for future research may be excluded from this study.
  -  Healthy volunteers who are pregnant or nursing will be excluded from all procedures with the exception of blood, urine, saliva, and/or buccal swab collection.

Relevance to patient case: not relevant