Table 1.
Clinical features of telomere biology disorders and health care recommendations
| Organ system | Features | Surveillance | Management |
|---|---|---|---|
| Mucocutaneous | Classic triad: nail dysplasia, abnormal skin pigmentation (hyper/hypopigmentation), oral leukoplakia Additional features: premature graying, scalp or eyelash hair loss, adermatoglyphia, palmoplantar hyperkeratosis, hyperhidrosis, epiphora, blepharitis |
Regular skin self-examination and annual full body skin exam by dermatologist | Regular use of sunscreen, advise to avoid excessive sun exposure |
| Hematologic | Cytopenias, BMFa, isolated aplastic anemia | Baseline CBC, bone marrow aspiration and biopsy with careful morphologic examination and cytogenetic studies (G-banding and FISH). If CBCs are normal and stable, annual CBC to identify trends and early manifestations. Annual bone marrow evaluation based on clinical features |
Early referral to an HCT transplant center with expertise in TBDs Participation in a clinical trial is encouraged. Consider oral androgens, such as danazol, for cytopenias. Improvement in cytopenias may take 4-8 weeks of androgens. If on androgen therapy: CBCs prior to therapy, repeat CBCs every 4-6 weeks to assess response when counts are stable every 2-3 months. Monitor more frequently if cytopenias change or a cytogenetic clone is identified. |
| Immunologic | Immunodeficiency (lymphopenia, decreased, T-, B- and natural killer cell count, hypogammaglobulinemia) | Consider a complete immunological evaluation including lymphocyte subsets, lymphocyte proliferation response, serum IgG, IgM, IgA levels, childhood vaccine antibody titers | Follow-up according to clinical features. Childhood vaccines, including HPV and influenza, if not contraindicated due to immunodeficiency or HCT. |
| Central nervous system | Brain structure: microcephaly, cerebellar hypoplasia/atrophy, intracranial calcifications, intracranial cysts Neurological: learning difficulty, developmental delay (psychomotor and mental), ataxia Psychiatric: mood disorders, schizophrenia |
MRI assessment for cerebellar hypoplasia at diagnosis in children or individuals with developmental delay or learning problems | Regular evaluation for developmental delay and early intervention if needed. Assess for mood disorders and related illnesses. |
| Ophthalmologic | Lacrimal duct stenosis, epiphora, blepharitis, entropion, trichiasis, keratoconjunctivitis, cataracts, ulcers Retinal abnormalities: retinal detachment, pigmentary changes, exudative retinopathy, proliferative retinopathy Corneal limbal insufficiency |
Annual examination to detect/correct vision problems, abnormally growing eyelashes, lacrimal duct stenosis, retinal changes, bleeding, cataracts, and glaucoma | |
| Otolaryngology | Oral leukoplakia and high risk of HNSCC Reduced hearing reported |
Annual cancer screening by a dentist and an otolaryngologist beginning in adolescence. Patient should be taught how to perform a monthly self-examination for oral, head, and neck cancer Baseline hearing evaluation |
Follow oral leukoplakia carefully and biopsy any changes or suspicious sites. |
| Dental | Oral leukoplakia and high risk of HNSCC Caries, periodontitis, decreased crown/root ratio, taurodontism46,47 |
Dental hygiene and screening every 6 months Maintain good oral hygiene Inform the primary dentist of the patient's increased risk of HNSCC |
|
| Cardiac | Atrial septal defect, ventricular septal defect, dilated cardiomyopathy, reported but not common | Baseline evaluation for PVAMs and cardiac malformations. Bubble echocardiogram for pulmonary symptoms in the absence of PF | Check lipid profile prior to starting androgens and monitor every 6-12 months while on androgens.52 |
| Pulmonary | PF, hepatopulmonary syndrome, PAVMs, interstitial pneumonitis, hypersensitivity pneumonitis, pleuroparenchymal fibroelastosis, pulmonary emphysema, combined PF and emphysema | Baseline PFTs at diagnosis and annually, beginning at an age when the patient can properly perform the test Counsel patients to avoid exposure to cigarette smoke |
Early referral to specialist for shortness of breath or unexplained cough. Antifibrotics for PF require further study in TBDs. Clinical trial participation is encouraged. |
| GI and liver | Esophageal narrowing/stricture/webs, dysphagia, failure to thrive, enteropathy/enterocolitis48 Noninfectious/nonalcoholic liver fibrosis/cirrhosis, nodular regenerative hyperplasia/noncirrhotic portal hypertension |
Evaluate for clinical history suspicious for esophageal stenosis and/or enteropathy and refer as needed Liver function tests at least annually Upper and/or lower endoscopy based on symptoms |
If on androgen therapy: Check liver function tests prior to starting, then every 6-12 weeks. Check lipid profile prior to starting and every 6-12 months. Perform liver ultrasound examination prior to initiation of androgens and semiannually to evaluate for adenomas, carcinomas, or fibrosis. |
| Vascular | Gastrointestinal telangiectatic anomalies and GI bleeding, PAVMs, retinal vessel abnormalities | Assess for GI bleeding and PAVMs as above Ophthalmic evaluations as above |
Early referral to experts in vascular anomalies. Propranolol and bevacizumab have been tried in a few patients but not systematically studied.44 |
| Genitourinary | Urethral stenosis/strictures/phimosis, undescended testes (rare), males: hypospadias, penile leukoplakia; females: urethral stricture, vaginal atrophy, leukoplakia | Baseline assessment for genitourinary anomalies, including symptoms of urethral stenosis | Assess for signs or symptoms of urethral stenosis. |
| Reproductive | Infertility reported in 1 case study, normal fertility in women with DC/TBD analyzed for pregnancy-related complications | Annual gynecologic evaluation with HPV testing starting at 18 years of age or at start of sexual activity Referral to maternal fetal medicine specialist for high-risk pregnancy |
|
| Endocrine | Short stature, hypogonadism (male) reported but not common | Follow growth carefully | If on androgen therapy: evaluation prior to therapy, during treatment conduct regular (annual) evaluation for side effects. |
| Skeletal | Osteopenia, osteoporosis, AVN of hips and shoulders49 | Baseline bone density scan to evaluate for osteopenia at ~14 years of age. Follow-up bone density scans yearly or as recommended by physician. Evaluation of hip and shoulder AVN based on symptoms | Vitamin D and calcium as needed to optimize bone health. If on androgen therapy: in growing child baseline prior to treatment, then every 6-12 months.53 |
| Other | Intrauterine growth retardation, low birth weight47 | Evaluations for developmental delay as above | |
| Reported malignancies | AML, MDS, HNSCC (especially tongue), NHL, anal SCC; skin: BCC, SCC Reported but rare: esophagus, rectal adenocarcinomas, cervix, thyroid, Hodgkin lymphoma, PTLD,12 lung, stomach, pancreas, colon, hepatic adenoma, hepatic angiosarcoma |
Annual evaluations by organ system as above | Increased sensitivity to therapeutic radiation and chemotherapy may require dose reductions. |
BCC, basal cell carcinoma; CBC, complete blood count; HNSCC, head and neck squamous cell carcinoma; MRI, magnetic resonance imaging; NHL, non-Hodgkin lymphoma; PFTs, pulmonary function tests; PTLD, posttransplant lymphoproliferative disease; SCC, squamous cell carcinoma.
a
Classification of BMF