Table 2:
Clinical features of telomere biology disorders.
| Organ system | Features |
|---|---|
| Mucocutaneous | Classic triad: Nail dysplasia, abnormal skin pigmentation (hyper/hypopigmentation), oral leukoplakia Additional features [92]: Premature greying, scalp or eyelash hair loss, adermatoglyphia, palmoplantar hyperkeratosis, hyperhidrosis, epiphora, blepharitis |
| Hematologic | Cytopenias, bone marrow failure, isolated aplastic anemia |
| Immunologic | Immunodeficiency (lymphopenia, decreased, T, B and NK cell count, hypogammaglobulinemia)[100,176,177] |
| 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 [178], schizophrenia [179] |
| Ophthalmologic | Lacrimal duct stenosis, epiphora, blepharitis, entropion, trichiasis, keratoconjunctivitis, cataracts, ulcers [131] Retinal abnormalities: retinal detachment [131], pigmentary changes [131], exudative retinopathy, proliferative retinopathy Corneal limbal insufficiency [180] |
| Oropharynx | Reduced hearing/deafness [110,181] |
| Dental | Caries, perodontitis, decreased crown/root ratio, taurodontism [110,182] |
| Cardiac | Atrial septal defect, ventricular septal defect, dilated cardiomyopathy, reported but not common [112,183] |
| Pulmonary | Pulmonary fibrosis, hepatopulmonary syndrome, pulmonary arteriovenous malformations, interstitial pneumonitis, hypersensitivity pneumonitis[117], pleuroparenchymal fibroelastosis [117], pulmonary emphysema [9,13], combined pulmonary fibrosis and emphysema [9,184] |
| Gastrointestinal and liver | Esophageal narrowing/stricture/webs, dysphagia, failure to thrive, enteropathy/enterocolitis [185] Noninfectious/nonalcoholic liver fibrosis/cirrhosis, nodular regenerative hyperplasia/non-cirrhotic portal hypertension |
| Vascular | Gastrointestinal telangiectatic anomalies and GI bleeding, pulmonary arteriovenous malformations, retinal vessel abnormalities |
| Genitouritary | Urethral stenosis/strictures/phimosis [110], undecended testes (rare)[110], males: hypospadias, penile leukoplakia, females: urethral stricture, vaginal atrophy and leukoplakia [112] |
| Reproductive | Infertility reported in one case study [89], normal fertility in women with DC/TBD analyzed for pregnancy related complications [186]. |
| Endocrine | Short stature [110], hypogonadism (male) [110], reported by not common |
| Skeletal | Osteopenia, osteoporosis [110,187], avascular necrosis of hips and shoulders [55] |
| Other | Intrauterine growth retardation, low birthweight [110] |
| Reported malignancies | AML, MDS, HNSCC (especially tongue), NHL, anal SCC, Skin: BCC, SCC Reported but rare: esophagus, rectal adenocarcinomas, cervix, thyroid, Hodgkin, PTLD (all reported in [12]), lung [117], stomach [188], pancreas, colon, hepatic adenoma [112], hepatic angiosarcoma [189,190], |
| Most common causes of death | Bone marrow failure, malignancies, pulmonary fibrosis |
References are noted for clinical features not specifically mentioned or explained in the text.
Abbreviations: AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; HNSCC, head and neck squamous cell carcinoma; SCC, squamous cell carcinoma; NHL, non-Hodgkin lymphoma; PTLD, post-transplant lymphoproliferative disease; BCC, basal cell carcinoma; GI, gastrointestinal