Prospective observational study to further understand the value that a multi-omic approach has in individuals with a multi system, early onset disorder that does not have a molecular diagnosis by whole genome sequencing.

Understand the value and utilization of integrated multi-omics, in multi-system early onset disorders that have failed to yield findings by whole genome sequencing

Inclusion Criteria:

• Undiagnosed probands must meet all of the following:

  1. Must be able to understand and sign an informed consent and speak, read, and write in their native language (if the subject is a minor, their parent must have these abilities)
  2. Proband between the ages of 12 months and 65 years
  3. Study consent and participation of at least two unaffected family members (biological parents preferred. One biological parent and unaffected sibling allowed)
  4. If applicable, unaffected sibling must be between the ages of 12 months and 65 years
  5. A high prior probability of a multi-system early onset undiagnosed genetic disorder based on an expert medical assessment
  6. Clinical WGS that did not yield a definitive diagnosis
  7. It is preferred but not required that ancestry is from an under-represented population in current clinical genetic and translational research data repositories, especially African American, Asian American and Native American
  8. Must be willing to have blood, urine and fecal samples taken to include participating family members

Diagnosed probands must meet all of the following:

1. Must be able to understand and sign an informed consent and speak, read, and write in their native language (if the subject is a minor, its Parent or Legally Authorized Representative must have these abilities).
2. Proband between the ages of 12 months and 65 years
3. Study consent and participation of at least two unaffected family members (biological parents preferred. One biological parent and unaffected sibling allowed)
4. If applicable, unaffected sibling must be between the ages of 12 months and 65 years
5. Known genetic cause(s) of disease, disorder, or phenotypic defect through prior clinical whole genome sequencing
6. It is preferred but not required that ancestry is from an under-represented population in current clinical genetic and translational research data repositories, especially African American, Asian American and Native American
7. Must be willing to have blood, urine and fecal samples taken to include participating family members

Exclusion Criteria:

• Undiagnosed probands must not meet any:

  1. Known non-genetic cause(s) of disease, disorder, or phenotypic defect
  2. Principal Investigator decides that the study is not in the best interest of the proband

Diagnosed probands must not meet any:

1. Principal Investigator decides that the study is not in the best interest of the proband

Outpatient setting with eighty percent consisting of prior negative genome cases that have previously received a clinical whole genome sequencing (cWGS) test. Remaining twenty percent will be positive controls who previously have a definitive diagnosis from clinical genetic testing.