The Telomere Clinic on the Sidney Kimmel Complete Most cancers Heart at Johns Hopkins gives multidisciplinary care to sufferers who’re suspected to have or who carry the analysis of telomere-related problems. Learn the newest analysis information.
Threat Elements
Telomere syndromes, together with dyskeratosis congenita, are brought on by abnormally brief telomeres, that are the protecting ends of chromosomes. When telomeres turn into abnormally brief, cells can now not divide successfully. An inherited mutation (change within the DNA code) within the gene that produces the telomere-lengthening enzyme referred to as telomerase disables the enzyme and causes telomeres to shorten at a quicker price.
Probably the most generally mutated genes in telomere syndromes are TERT (which stands for telomerase reverse transcriptase) and TR (often known as TERC). Mutations within the DKC1 gene, situated on the sex-linked X chromosome, and TINF2 may also trigger dyskeratosis congenita and its associated problems. In some instances, inherited mutations in an affected household can’t be discovered, although brief telomeres are recognized in members of the family. As a result of inherited mutations aren’t all the time discovered amongst sufferers’ households, telomere syndromes are identified in sufferers who’ve a mixture of abnormally brief telomeres together with particular medical options. Johns Hopkins investigators are conducting analysis to determine extra genetic causes of telomere syndromes.
Signs
Signs of telomere syndromes range and depend upon every affected person’s telomere size. Some sufferers have few or no signs. The situations embrace:
Bone Marrow Failure – a critical symptom of dyskeratosis congenita, bone marrow failure happens in lots of youngsters with the situation. Bone marrow failure generally happens when sufferers expertise thrombocytopenia, a low variety of blood-clotting cells referred to as platelets, or neutropenia, a low variety of white blood cells that play a task within the physique’s immune system.
Pulmonary fibrosis – Pulmonary fibrosis, or scarring of the lung, is the commonest symptom of telomere syndromes, and normally impacts adults who might not have bone marrow failure. It additionally happens in youngsters who’ve undergone bone marrow transplantation.
Liver illness – Scarring of the liver (cirrhosis) will also be a complication of telomere syndromes, and sufferers who expertise this usually have an enlarged spleen.
Gastrointestinal illness— In extreme instances amongst younger youngsters, telomere problems could cause remoted issues within the intestine, together with bloody diarrhea and inadequate weight acquire and bodily progress referred to as failure to thrive.These signs usually seem in sufferers with a uncommon telomere dysfunction often called Hoyeraal-Hreidarsson syndrome.
Pores and skin and mucosal abnormalities – In dyskeratosis congenita, sufferers’ pores and skin might have irregular pigmentation, with an absence or overabundance of spots and patches. The pigmentation sample sometimes seems on sun-exposed areas of the face, neck and higher trunk. A situation referred to as leukoplakia, which might seem as white patches on the insides of the mouth may also happen. Different signs can embrace hair graying at a younger age and nail weak point or splitting together with ridging.
Different signs embrace eye issues (reminiscent of extreme tearing), skeletal issues (reminiscent of osteoporosis or weak point of bone tissue within the hips or elsewhere), or narrowing of the esophagus, referred to as stenosis.
Most cancers threat — In a small subset of sufferers, telomere syndromes could also be related to elevated most cancers threat. These cancers might seem on the pores and skin or within the mucosal membranes within the mouth and elsewhere. Cancers of the bone marrow reminiscent of myelodysplastic syndrome or acute leukemia, may also happen.
Hoyeraal-Hreidarsson syndrome could be very uncommon and is normally identified within the first years of life and represents a extreme type of telomere syndromes. It’s characterised by small weight, failure to thrive, and cerebellar and immune abnormalities.
Prognosis
Telomere syndromes are identified in sufferers who’ve signs related to the situation and abnormally brief telomeres size. In 20 – 60 p.c of sufferers, a genetic change (mutation) in a gene related to telomere syndromes could also be recognized.
Therapy
Timing of therapy –In lots of delicate instances the place the speed of development is sluggish, sufferers might not require therapy for a few years. Therapy selections are individualized to every affected person and mentioned with clinicians who’re skilled in treating this situation.
Drugs – Anecdotal experiences of utilizing steroid medication (often called androgens) in sufferers with bone marrow failure have been proven to enhance blood cell counts.
Stem cell transplant/Bone marrow transplant – Therapy for extreme bone marrow failure problems on account of telomere shortening is bone marrow/stem cell transplantation, by which a affected person’s bone marrow or peripheral blood stem cells are changed with these from a wholesome donor. Telomere syndrome sufferers are susceptible to uncomfortable side effects from sure medication utilized in commonplace transplants and will endure a modified transplant regiment in a middle with expertise on this specific situation. At Johns Hopkins, we have now efficiently carried out bone marrow transplants for this situation.
Lung and liver illness– Lung or liver transplantation may additionally be acceptable for some sufferers whose pulmonary fibrosis or liver cirrhosis are the first problems.
Extra info on bone marrow transplants
The Telomere Clinic at Johns Hopkins
The Telomere Clinic on the Sidney Kimmel Complete Most cancers Heart at Johns Hopkins gives multidisciplinary care to sufferers who’re suspected to have or who carry the analysis of telomere-related problems, together with dyskeratosis congenita, most cancers, bone marrow failure/aplastic anemia, and lung illness together with idiopathic pulmonary fibrosis and liver cirrhosis. Our clinic brings collectively geneticists and genetic counselors working intently with skilled physicians in grownup and pediatric hematology, bone marrow transplant, pulmonary medication, hepatology, and otolaryngology. For the previous 10 years, our crew has pioneered the administration of those problems and are skilled in individualizing look after sufferers and their households. To schedule appointments, name 410-955-8964.
Telomere Size Measurement for Medical
In 2016, a clinically-certified check to find out telomere size in sufferers suspected to have telomere syndromes has turn into obtainable to clinicians all over the world via the Johns Hopkins Hospital. Pathology Laboratories. For questions associated to this testing, please contact Mary Armanios, M.D. at [email protected] or [email protected].
Alternatives to Advance Care via Analysis
At Johns Hopkins, there’s a thriving analysis effort to advance the care of sufferers with telomere syndromes. Over the previous decade, medical and primary science researchers have been working collectively to outline new standards for outlining signs for these situations to facilitate their recognition and to grasp their genetic foundation.
Amongst analysis efforts led by Mary Armanios, M.D., is a long-term research to grasp the pure historical past, genetics and spectrum of brief telomere syndromes. Greater than 300 sufferers have enrolled within the Johns Hopkins-based Telomere Syndrome Registry which gathers info supplied by sufferers with a view to advance this space.
As well as, Johns Hopkins clinicians and scientists are learning how telomere problems trigger stem cell failure and pulmonary fibrosis with the objective of advancing the therapy of those situations. The distinguished scientific crew is led by Dr. Carol W. Greider, Professor and Director of the Division of Molecular Biology and Genetics and the recipient of the 2009 Nobel Prize in Drugs for the co-discovery of telomerase.
