Table 2.

Diagnosis, associated malignancies, and management recommendations for DNA repair and telomere biology disorders

	Diagnostic Testing and Other Biomarkers	Associated Malignancies	Management Recommendations
Ataxia Telangiectasia	Genetic testing Newborn screening: reduced T-cell receptor excision circle levels Elevated alpha fetal protein Karyotype: 7:14 chromosomal translocation Immunoblotting (research) Chromosome breakage studies for radiation sensitivity (research)	Lymphoma, ALL, ovarian cancer, breast cancer, gastric cancer, melanoma, leiomyomas, sarcomas	Hematology-Oncology: History/physical, annual complete blood counts, metabolic profile and lactate dehydrogenase and avoid excessive radiation. Immunology: monitoring of immunoglobulin levels per immunologist recommendation. Dermatology: annual skin exam Pulmonary: baseline and as needed pulmonary function tests. Gastroenterology/Nutrition: baseline and as needed swallowing function and nutritional management Endocrine: annual diabetes screen Neurology: supportive medications Orthopedics: annual scoliosis evaluation Dental: biannual exam
Bloom’s Syndrome	Genetic testing Chromosome breakage with DEB and/or MMC abnormal sister chromatid exchange (research)	Lymphoma, AML, ALL, sarcoma, genital and urinary tract carcinoma, medulloblastoma, retinoblastoma	Hematology-Oncology: annual complete blood counts, avoidance of radiation; breast MRI/ultrasound starting between 20–25 years of age, colonoscopy starting at age 15 every 2 years and fecal occult blood every 6 months starting at age 15 Dermatology: annual skin exam, limit sun exposure Pulmonary: pulmonary function tests Gastroenterology/Nutrition: baseline and as needed swallowing function evaluation and nutritional management Endocrine: annual diabetes screen Genitourinary: congenital anomaly evaluation at diagnosis Orthopedics: annual scoliosis evaluation Dental: biannual exam
Dyskeratosis Congenita	Genetic testing Telomere length measurement of leukocyte subsets using flow cytometry with in situ hybridization	Head and neck SCC, AML, MDS, anogenital cancer	Hematology-Oncology: annual CBCs, ~annual bone marrow evaluations based on clinical features, early referral to HCT center, HPV vaccine, annual ENT evaluation beginning in adolescence Immunodeficiency: monitoring of immunoglobulin levels per immunologist recommendation. Dermatology: annual skin exam Pulmonary: baseline pulmonary function tests with routine follow-up Gastroenterology/Nutrition: liver function tests at least annually, more frequent if on androgens Endocrine: annual diabetes screen Neurology: MRI assessment for cerebellar hypoplasia at diagnosis, early intervention for developmental delay Ophthalmology: annual examination, monitoring and early management of lacrimal duct stenosis Orthopedics: evaluation of hip and shoulder avascular necrosis based on symptoms Dental: biannual exam ENT: baseline hearing evaluation
Fanconi Anemia	Genetic testing Chromosomal breakage with DEB and/or MMC	Head and neck SCC, AML, MDS, anogenital cancer	Hematology-Oncology: annual CBCs, ~annual bone marrow evaluations based on clinical features, early referral to HCT center, HPV vaccine, annual ENT evaluation beginning in adolescence Immunology: monitoring of immunoglobulin levels per immunologist recommendation. Dermatology: annual skin exam Pulmonary: baseline pulmonary function tests with follow-up as needed Gastroenterology/Nutrition: annual liver function tests, more frequent if on androgens Endocrine: annual diabetes screen, follow growth trajectory Orthopedics: assessment of radial ray anomalies and management, if needed Genitourinary: baseline evaluation for renal malformations Cardiology: baseline evaluation for heart malformations ENT: annual hearing evaluation, annual cancer screening starting in teenage years Dental: biannual exam
Nijmegen Breakage Syndrome	Genetic testing Chromosomal Breakage with DEB and/or MMC Chromosomal instability involving chromosomes 7 and 14 in PHA stimulated lymphocytes Immunoblotting (research)	Lymphoma, medulloblastoma, glioma, rhabdomyosarcoma	Hematology-Oncology: Hematology-Oncology: History/physical, annual complete blood counts, metabolic profile and lactate dehydrogenase and avoid excessive radiation. Dermatology: annual skin examinations Pulmonary: baseline pulmonary function tests with follow-up as needed, aggressive treatment of recurrent infections Gastroenterology/Nutrition: baseline and as needed swallowing function evaluation and nutritional management Endocrine: monitor growth, assess females assess for ovarian failure Neurology: developmental assessment and early intervention if needed Ophthalmology: annual examination Orthopedics: baseline assessment for anomalies and as needed Dental: biannual exam
Rothmund-Thomson Syndrome	Genetic testing	Osteosarcoma, basal cell carcinoma, skin SCC	Oncology: avoid ionizing radiation, consider imaging for osteosarcoma risk Dermatology: Avoid excessive UV; use sunscreen annual exam and early treatment of lesions Ophthalmology: annual evaluation and cataract treatment as needed Endocrine: management for osteopenia Orthopedics: baseline skeletal survey Dental: biannual evaluation with proper care for hypoplastic teeth, enamel defects
Xeroderma Pigmentosa	Genetic testing	Melanoma, basal cell carcinoma, skin SCC, leukemia, brain and spinal cord tumors	Oncology: beginning at diagnosis - avoid excessive sunlight and ionizing radiation; early identification and treatment of skin lesions; exam for ocular and ENT neoplasms every 6–12 months Dermatology: thorough skin evaluation every 3 months Gastroenterology/Nutrition: evaluate swallowing function, nutritional support, as needed Ophthalmology: exam every 6–12 months Neurology: evaluation for developmental delay or progressive neurologic changes Orthopedics: annual scoliosis evaluation ENT: baseline hearing evaluation and as needed, cancer screening every 6–12 months

Abbreviations: AML, acute myeloid leukemia; ALL, acute lymphocytic leukemia; CBC, complete blood count; DEB; diepoxybutane; ENT, ear, nose and throat; IVIg, intravenous immunoglobulin; MDS, myelodysplastic syndrome; MMC, mitomycin C; PHA, phytohemagglutinin; SCC, squamous cell carcinoma