The RTEL1 gene is associated with two disorders called Hoyeraal-Hreidarsson syndrome and dyskeratosis congenita. These inherited disorders impair the proper maintenance of chromosome ends (telomeres) and DNA repair leading to a wide variety of symptoms.
Hoyeraal-Hreidarsson syndrome (HHS) is associated with growth restriction in utero and after birth, a small or missing cerebellum (part of the brain that coordinates movement), severe developmental delay, microcephaly (small head size), and immunodeficiency as a result of bone marrow failure. Most individuals with HHS die in childhood as a result of these symptoms.
Dyskeratosis congenita (DKC) is clinically less severe than HHS and is characterized by three main symptoms: abnormal skin coloring specifically in the upper body, leukoplakia (white patches on the tongue and inside of the mouth), and abnormal nails of the fingers and toes. Other symptoms of DKC include short stature, dental abnormalities, fibrosis (thick scarring) in the lungs and liver, narrowing of the esophagus, narrow urethra (typically only in males), osteoporosis (weak or brittle bones), progressive bone marrow failure, and cancer (most commonly leukemia). Progressive bone marrow failure and cancer are the most common causes of death. Most people with DKC have normal intelligence and development, but there are reports of individuals who are more severely affected may have varying degrees of intellectual disability or developmental delay. These symptoms are variable, as not all individuals with DKC will have the same presentation. Mutations in RTEL1 make up to 2-8% of all cases of DKC.
Approximately 1 in 100 individuals in the Ashkenazi Orthodox and 1 in 222 individuals in the Ashkenazi Jewish population are reported to be carriers for a mutation in the RTEL1 gene. In the general population, RTEL1-related disorders affect about 1 in 1,000,000 individuals.
There is no cure for RTEL1-related disorder. Regular screening for bone marrow failure and leukemia is recommended with hematopoietic stem cell transplantation used as a treatment option if needed. Annual pulmonary function tests to assess for fibrosis as well as periodic follow-up with a multidisciplinary team of specialists is recommended to assess for other symptom development.
The prognosis for an individual with HHS is typically poor as it often leads to early bone marrow failure and premature death in childhood. The prognosis for an individual with DKC is variable and is dependent on the severity. The average life expectancy is about 30 years, although many die around the age of 15 as a result of bone marrow failure, lung complications, or cancer.
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Explanations of an extensive number of genetic diseases written for everyday people by the U.S. government's National Institutes of Health.