It is widely known in the scientific community that critically short telomeres are often involved in age related diseases. In particular, growing evidence demonstrates that there is a type of disorders directly related to telomeres with important implications for both doctors and patients: the telomeropathies.

The telomeropathies  are inherited conditions caused by genetic defects in the telomere maintenance machinery. This is to say, these pathologies are directly caused by the unusual shortening of telomeres, product of alterations in the genes involved in telomere care. They might be found referred to as “telomeropathies,” “telomere disorders” or “telomere syndromes” and widely acknowledge as impaired telomere maintenance spectrum disorders.

The age of onset is highly variable, affecting both children and adults. Still, they share some common traits that we will try to expose as follows. The symptoms of these disorders are extensive, but mainly these conditions include:

  -Bone Marrow Failure (inability of bone marrow to produce sufficient blood cells) which leads to hematological conditions

  – Lung disease

  – Liver disease

  – Skin and mucosal abnormalities, mainly abnormal pigmentation of the skin

  – Gastrointestinal disease, as insufficient weight gain or bloody diarrhea

  – Cancer predisposition

In adulthood, the most common telomere syndrome is Idiopathic Pulmonary Fibrosis (IPF). IPF is characterized by the dysfunction and progressive failure of lung function. Other manifestations of impaired telomere maintenance in adults include diseases such as familial liver cirrhosis, aplastic anemia or sporadic acute myelogenous leukemia (AML). At times, the clinical presentation and symptoms occur concurrently; indicating that telomere shortening occurs throughout the body even in patients that display failure of a single organ. In other words, the common underlying cause is impaired telomere maintenance, so it may be appropriate to consider them a single clinical spectrum disorder.

Dyskeratosis congenita (DKC) was the first disorder linked to impaired telomere maintenance. Individuals with DKC display organ failure and blood disorders and is characterized by abnormal findings in the mouth, skin and nails. DKC overlaps significantly in pathology and genetic cause with Hoyeraal-Hreidersson syndrome (HHS), Coats Plus syndrome, and Revesz syndrome, which are severe forms of telomeropathies.   

In addition to the aforementioned classically linked disorders, a number of diseases not typically associated with telomere biology are reported to be caused by faults in DNA repair proteins that contribute to telomere preservation. We refer to these as peripheral or secondary telomeropathies because it is unresolved if the reported telomere dysfunction in these contexts is the cause or just one of the effects of the diseases.

Nowadays, the only palliative therapy for some of these syndromes is tissue or organ transplant from a healthy, matching donor. In the future, it may be possible to perform autologous stem cell transplantation after in vitro transient lengthening of telomeres.

In summary, telomere maintenance spectrum disorders present a variety of shared symptoms and the age of their onset is highly variable. Interestingly these disorders share similar, underlying molecular mechanisms leading to premature telomere shortening leading to a spectrum of diseases that are only recently being recognized. Though much is already known about the biology of telomeropathies, important unanswered questions remain. The discovery of new correlations between human syndromes and telomere disorders are to be expected in the future.