Four rare genetic diseases, xeroderma pigmentosum (XP), Cockayne syndrome (CS), the XP/CS complex and trichothiodystrophy (TTD) have defective DNA excision repair although only XP has increased cancer susceptibility. We plan to perform careful clinical examination of selected patients with XP, XP/CS, CS, or TTD and follow their clinical course. We will obtain tissue (skin, blood, hair, buccal swabs) for laboratory examination of DNA repair and for genetic analysis. We hope to be able to correlate these laboratory abnormalities with the clinical features to better understand the mechanism of cancer prevention by DNA repair. Patients will be offered counseling and education for cancer control.

Three rare genetic diseases, xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD) have defective DNA excision repair although only XP has increased cancer susceptibility. We plan to perform careful clinical examination of selected patients with XP, CS, TTD, or overlap syndromes to follow their clinical course. We will obtain tissue (skin, blood, hair, or buccal cells) for laboratory examination of DNA repair and for histologic, protein, biochemical, and genetic analysis. We hope to be able to correlate these laboratory abnormalities with the clinical features to better understand the mechanism of cancer prevention by DNA repair. Patients will be offered counseling and education for cancer control.

• INCLUSION CRITERIA:

• Subjects age 6 weeks and above:

  • with clinical and/or laboratory documentation of typical features or suggestive clinical features of XP, CS, TTD, or overlap syndromes or
  • that are first degree relatives or other family members of participants with XP, CS, TTD, or overlap syndromes

• Healthy volunteers of age 1 year and above (including NIH employees) willing to donate blood, skin, buccal cells, or hair.

• Patients or legally authorized representatives must provide informed consent.

EXCLUSION CRITERIA:

-Inability or unwillingness to provide tissue (skin, blood, buccal cells or hair) for laboratory studies.

Patients will be sought by contacting professional organizations (such as the American Academy of Dermatology-XP Task Force), lay support groups (such as the XP Society and the Share and Care CS Support Network) or by direct referral. Healthy volunteers or NIH staff will be recruited through the Program for Healthy Volunteers (CRVP@mail.cc.nih.gov), through the Patient Recruitment and Public Liaison Office (prpl@mail.cc.nih.gov), or as a self-referral through the clinicaltrials.gov web site (http://clinicaltrials.gov). Healthy volunteers may also be approached by a member of the LCBG, NCI regarding interest in participating on this protocol.

All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

-Clinical data available during the study and indefinitely.@@@@@@-Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active

-Clinical data will be made available and with the permission of the study PI.@@@@@@-Genomic data are made available via dbGaP through requests to the data custodians.