Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy

Conditions
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Trichothiodystrophy Syndromes, Genodermatosis, Cockayne Syndrome, Skin Neoplasms, Xeroderma Pigmentosum

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Subjects with clinical and/or laboratory documentation of typical features or suggestiveclinical features of XP, CS, TTD, or overlap syndromes | |
| 2<br>Family members of patients with XP, CS, TTD, or overlap syndromes | |
| 3<br>Healthy volunteers | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify patients with genetic diseases | Proportion of patients with three rare genetic diseases; xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD)and overlap syndromes | Up to 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis confirmation | -To confirm suspected cases of XP, CS, TTD, XP/TTD or overlap syndrome patients by review of clinical records, by clinical examination and by laboratory testing -To document presence (or absence) of cancers (skin, eye, tongue, or internal) in XP, XP/CS, CS, TTD, XP/TTD and other overlap syndrome patients-To document atypical clinical features or unusual environmental exposures of patients with XP, XP/CS, CS, TTD, XP/TTD and otheroverlap syndromes | up to 3 days | 
| Tissue collection | obtain tissue (skin, blood, hair or buccal cells) from XP, CS, TTD, XP/TTD or overlap syndrome patients, their first-degree relatives and healthy volunteers for establishment of cell cultures and for examination of DNA repair and genetic analysis | up to 3 days | 
| identify molecular defects | identify molecular defects in the DNA repair or other genes in cells from patients with XP, CS, TTD, XP/TTD or overlap syndromes and toattempt to correlate the defects with the clinical features | up to 3 days | 
| overall survival | follow the clinical course of selected patients with XP, CS, TTD, XP/TTD or overlap syndromes | yearly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xeroderma Pigmentosum, Trichothiodystrophy, Cockayne Syndrome, Skin Cancer, DNA Repair, Natural History