The RTEL1 gene is linked to two disorders called Hoyeraal-Hreidarsson syndrome and dyskeratosis congenita. These inherited conditions affect the proper maintenance of chromosome ends (telomeres) and DNA repair, causing various symptoms.
Hoyeraal-Hreidarsson syndrome (HHS) is linked to restricted growth before and after birth, a small or missing cerebellum (part of the brain for movement coordination), severe developmental delay, a small head (microcephaly), and weakened immune system due to bone marrow failure. Sadly, most individuals with HHS pass away in childhood because of these symptoms.
Dyskeratosis congenita (DKC) is generally less severe than HHS and shows three main symptoms: unusual skin coloring in the upper body, white patches on the tongue and inside the mouth (leukoplakia), and abnormal nails on fingers and toes. Other DKC symptoms include short stature, dental issues, thick scarring in the lungs and liver (fibrosis), narrowing of the esophagus, narrow urethra (mostly in males), weak or brittle bones (osteoporosis), ongoing bone marrow failure, and cancer (usually leukemia). Progressive bone marrow failure and cancer are the most common causes of death. Most people with DKC have typical intelligence and development, but some may experience varying degrees of intellectual disability or developmental delay. The symptoms can vary, and not everyone with DKC will show the same signs.
There’s no cure for RTEL1-related disorders. Regular screening for bone marrow failure and leukemia is advised, with hematopoietic stem cell transplantation as a treatment option if necessary. Regular pulmonary function tests and follow-ups with a team of specialists are recommended to monitor for other symptom developments.
This group of conditions is caused by pathogenic (disease-causing) variants in the RTEL1 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Ashkenazi Jewish descent have a 1 in 222 chance to be a carrier.