Patient case (clinical description): A 20-year-old man comes to the clinic for his routine checkup. The patient wears glasses for myopia and takes no medications.  Vital signs are normal.  On physical examination, the patient is tall with long upper extremities and fingers.  The face appears narrow with down-slanted palpebral fissures, flattened malar bones, and a small jaw.  The lungs are clear on auscultation.  The abdomen is soft with no organomegaly. The patient is diagnosed with Marfan syndrome, and he is cooperative with his medical appointments. He is working as driver.

Patient's own account: I'm a 20-year-old guy, working as a driver and I went to the clinic for my routine checkup. I have myopia, so I wear glasses and I don't take any other medications. My vitals were normal. I also did a physical exam, and I was told that I have long legs, arms, and fingers. They also told me that my face is quite narrow, with down-slanted eyes and a small jaw. My lungs were fine and my tummy too. I have been diagnosed with Marfan syndrome and I haven't been skipping any medical appointments since.

Clinical trial: Whole Genome Medical Sequencing for Genome Discovery

Eligibility criteria:
-  INCLUSION CRITERIA:

        An individual who is affected with a disorder under study. Our initial list of exemplar
        disorders has been discontinued; these disorders were examples of those which meet the
        general attributes for inclusion in this protocol. As stated above, individuals with
        disorders we choose to investigate under this protocol will generally represent simplex
        cases with rare phenotypes whose molecular etiology is unknown.

        In rare instances, we may accept DNA from deceased individuals, including DNA or other
        saved biological specimens from deceased fetuses/neonates in accordance with Policy 400.
        These samples may provide us exceptional opportunities to study variants and manifestations
        of severe genetic overgrowth disorders. In the rare circumstance where we plan to accept
        samples from fetuses/neonates, we may engage with pregnant mothers to begin consent
        discussions and coordinate specimen collection. We will only enroll pregnant women who
        voluntarily donate fetal tissue from invasive prenatal testing, and for which trio analysis
        is appropriate and necessary. While rare, there may be circumstances in which the
        scientific objectives (to elucidate the molecular etiology of the proband s genetic
        condition) would not be possible without analyzing the DNA of the fetus/proband and the
        biological parents.

        Family members of an affected individual where that family member (often a parent) is
        potentially informative or useful for linkage or other bioinformatic analyses of genetic
        variants may be enrolled. Probands who are minors or decisionally impaired adults are
        eligible if they have a parent or legal guardian who has authority to sign a consent form
        on their behalf.

        EXCLUSION CRITERIA:

        Probands who are adults and decisionally impaired are ineligible if they do not have a
        legal guardian who has authority to sign a consent form on their behalf.

        Subjects who have known, significant affective or psychiatric disorders that, in the
        judgment of the team, may impair their ability to understand and appropriately use complex
        medical and genetic information will be considered decisionally-impaired and will be
        ineligible unless they have appointed (or, in the case of minor children, are in the
        custody of) an appropriate surrogate decision-maker.

        In addition, guardianship for cognitively impaired adult probands must be legally
        established and proof of guardianship must be supplied prior to that family s enrollment.

        We request the ability to use this protocol for multiple genetic disorders, without
        specifically delineating them a priori. We believe this approach to be appropriate because
        for nearly all inherited disorders, the risks and benefits of GSMS do not substantively
        differ. This concept was validated by our now-closed protocol 94-HG-0193, which was a
        broad-based protocol for heritable congenital anomaly disorders, many of which do not fall
        neatly into a specific diagnostic classification.

        We may request permission to retain some information about prospective participants who, at
        the time of their inquiry, may not be eligible for the study but who could become eligible
        in the future. As these participants will not be signing a consent form, we propose to NOT
        count these participants in our Inclusion Enrollment Reports but will provide the IRB with
        a tally of retained records at each Continuing Review.

        Consent documents for this protocol are available in English and Spanish. In rare
        instances, we may enroll participants who speak other languages using the NIH Short Written
        Consent Form Translation.

        We will not enroll pregnant women, except as outlined in the section above.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 1 Month old.


Eligibility (NLI label): Entailment