Rothmund-Thomson syndrome
Rothmund-Thomson syndrome (RTS) is a rare inherited disorder characterized by a variety of symptoms affecting multiple body systems, primarily involving skin, bones, and vision. It is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the defective gene, specifically mutations in the RECQL4 gene, for a child to be affected. Symptoms typically emerge in infancy, with a distinctive rash developing by six months of age, leading to a chronic skin condition known as poikiloderma, which is marked by changes in skin color, texture, and the presence of blood vessels.
In addition to skin manifestations, individuals may experience skeletal abnormalities, growth delays, cataracts, dental issues, and an increased risk of cancers, especially bone cancer. Diagnosis is primarily based on clinical examination and genetic testing, while management focuses on monitoring and treating specific symptoms, such as cataract removal and skincare. Though the syndrome is not typically life-threatening, serious complications can arise if associated cancers are not addressed. RTS has been documented in various ethnic groups, indicating no specific demographic predisposition. Preventive measures, such as sun protection, are recommended to mitigate skin-related issues.
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Rothmund-Thomson syndrome
ALSO KNOWN AS: RTS, Rothmund dystrophy, Thomson’s disorder, poikiloderma congenitale
RELATED CONDITIONS: RAPADILINO syndrome, Baller-Gerold syndrome
DEFINITION: In 1868, August von Rothmund, a German ophthalmologist, published an account of a syndrome that included cataracts, a depressed nasal bridge, and skin degeneration with familial links. Then, in both 1923 and 1936, Matthew S. Thomson, a British dermatologist, reported a disorder with the same defining characteristics. After some controversy over whether the reports described the same disorder, the disease became known as Rothmund-Thomson syndrome. As suggested by the time between Rothmund’s and Thomson’s accounts, Rothmund-Thomson syndrome is extremely rare. It is an inherited disorder that affects many body systems and is usually diagnosed during early infancy, typically between the ages of three and six months.
Risk factors: Family history is the only known risk factor for Rothmund-Thomson syndrome. The disorder is inherited as an autosomal recessive trait, which means that both parents of an affected child have one copy of the defective gene that is responsible for the disorder but do not have the disorder themselves. If both parents have one copy of the defective gene, each of their children has a 25 percent chance of having both defective genes and the disorder, a 25 percent chance of not having the gene, and a 50 percent chance of having one defective gene, like the parents.
Etiology and the disease process: The defective gene responsible for Rothmund-Thomson syndrome is called adenosine triphosphate (ATP)-dependent deoxyribonucleic acid (DNA) helicase Q4, or RECQL4. Mutations in RECQL4 have been detected in about two-thirds percent of affected individuals. Mutations in ANAPC1, a gene important to DNA replication and repair, have also been implicated as playing a role in one type of Rothmund-Thomson syndrome. Additional genes are suspected to play a role, and more research is needed.
At birth, an affected child’s skin appears normal. Usually, by the age of six months, a characteristic rash has developed on the child’s face and later spreads to the buttocks and extremities. The rash eventually changes into a chronic pattern of several skin abnormalities, collectively known as poikiloderma. At birth and as the child ages, many other abnormalities may be diagnosed, including skeletal defects, growth delays, vision disturbances, and possibly bone and skin cancers. The clinical features, disease progression, and severity can vary from case to case.
Incidence: Only about 300 cases of Rothmund-Thomson syndrome have been reported in scientific literature. It does not seem to affect one group more than another, as it has been found in all races and many nationalities. More than 90 percent of patients develop the characteristic skin symptoms by their first birthday.
Symptoms: The initial rash that is characteristic of most cases of Rothmund-Thomson syndrome begins as abnormally red, swollen patches, usually on the face, that are accompanied by blistering and abnormal accumulations of fluid between the layers of tissue under the skin. Additional areas of the body become involved as the disorder progresses, including the arms, legs, hands, feet, and buttocks. Eventually, a collective group of findings, known as poikiloderma, begins. The swollen skin begins to shrink, groups of small blood vessels widen abnormally, and patchy areas of abnormally decreased or increased coloration appear. Skin that is exposed to the sun usually shows greater abnormalities, and the individual can develop thickened skin or cancerous skin changes later in life.
Skeletal abnormalities may be present from birth or develop as the child grows. They include unusually small, short hands and feet and underdeveloped or absent thumbs and forearm bones. The development of osteosarcoma, a bone cancer, can occur later in life. Affected individuals may also have characteristic abnormalities of the head and face, including a prominent forehead, sunken nasal bridge, and a protruding lower jaw. Growth delays can lead to shortened height. Some other common characteristics of Rothmund-Thomson syndrome that may begin in childhood include gray, sparse hair, absent eyebrows and eyelashes, cataracts, excessive cavities and unusually small or missing teeth, and abnormally developed nails. Irregular menstruation and delayed sexual development in women and reduced fertility in both sexes can also occur because of deficient activity of the ovaries in women or testes in men.
Screening and diagnosis: The only way to screen for Rothmund-Thomson syndrome is genetic testing for family members of affected individuals. The diagnosis of Rothmund-Thomson syndrome is usually based on physical examination and family history. Some skin cell and lymphocyte tests may show changes that have been seen with Rothmund-Thomson syndrome, but they are not considered diagnostic. Testing to determine the extent of the disorder and monitoring for complications includes X-rays for skeletal abnormalities, routine eye examinations for the early diagnosis of cataracts, endocrine tests, and a complete blood count.
Treatment and therapy: Treatment of Rothmund-Thomson syndrome primarily involves annual physical examinations to monitor for skin and bone changes as well as complications that develop as the person ages, such as endocrine deficiencies. Cataracts should be removed if they decrease vision. For cosmetic purposes, skin conditions can be treated with a variety of medications or laser therapy. People who develop cancer should receive treatment based on the type of cancer.
Prognosis, prevention, and outcomes: Rothmund-Thomson syndrome is not usually a life-threatening disease unless the individual develops bone cancer or allows skin cancer to go untreated. Use of sunscreen and avoiding repeated or excessive sun exposure are recommended. There is no prevention or cure for the disorder.
Bibliography
Broom, M. A., et al. “Successful Umbilical Cord Blood Stem Cell Transplantation in a Patient with Rothmund-Thomson Syndrome and Combined Immunodeficiency.” Clinical Genetics, vol. 69.4, 2006, pp. 337–43.
Goldsmith, Lowell A., Stephen I. Katz, Barbara A. Gilchrest, Amy S. Paller, David J. Leffell, and Klaus Wolff. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: McGraw, 2012.
Goodwin, Meredith. “What Is Rothmund-Thomson Syndrome? Symptoms, Causes, and More.” Healthline, 14 Feb. 2023, www.healthline.com/health/rothmund-thomson-syndrome#outlook. Accessed 16 June 2024.
Kumar, P., et al. “Late-Onset Rothmund-Thomson Syndrome.” International Journal of Dermatology, vol. 46.5, 2007, pp. 492–93.
Martins, Davi J., et al. "Rothmund-Thomson Syndrome, a Disorder Far from Solved." Frontiers in Aging, vol. 4, 2023, doi.org/10.3389/fragi.2023.1296409. Accessed 16 June 2024.
“Rothmund-Thomson Syndrome (RTS): Symptoms & Causes.” Cleveland Clinic, 10 Sept. 2022, my.clevelandclinic.org/health/diseases/24154-rothmund-thomson-syndrome-rts. Accessed 16 June 2024.
Wang, L. L., et al. “Association Between Osteosarcoma and Deleterious Mutations in the RECQ14 Gene in Rothmund-Thomson Syndrome.” Journal of the National Cancer Institute, vol. 95.9, 2003, pp. 669–74.
Wang, Lisa. “Rothmund-Thomson Syndrome - GeneReviews®.” NCBI, 4 June 2020, www.ncbi.nlm.nih.gov/books/NBK1237. Accessed 16 June 2024.