Rothmund-Thomson syndrome is the name given to a genetic skin disorder. Its inheritance is autosomal recessive.
What is Rothmund-Thomson syndrome?
Rothmund-Thomson syndrome (RTS) is one of the genetic skin diseases. In this case, there is marked poikiloderma, especially in the facial region, which is associated with orthopedic and ophthalmologic complaints. In addition, there is an increased risk of developing certain cancers. The name Rothmund-Thomson syndrome originates from the description of two physicians. It was first described in 1836 by the German ophthalmologist August von Rothmund (1830-1906). In 1936 two papers were published by the English physician Matthew Sydney Thomson (1894-1969), which dealt with hereditary poikiloderma (Poikiloderma congenitale). This disease is the same as the diseases described by August von Rothemund. For this reason, it was later given the name Rothmund-Thomson syndrome. Rothmund-Thomson syndrome can be counted among the rare diseases. Until 2014, only 300 cases of the disease were registered. The syndrome is familial, which is typical for hereditary diseases. Blood relatives or small communities are primarily affected. There is a balance between the two sexes in the number of cases. However, due to low case numbers, no precise information can be given. Furthermore, no particular ethnic group is particularly affected by Rothmund-Thomson syndrome. The carrier frequency of the mutation is not known.
Causes
In medicine, Rothmund-Thomson syndrome is divided into the subtypes RTS-1 and RTS-2. It has not yet been possible to clarify what causes RTS-1. RTS-2 can be attributed to a heterozygous mutation originating in the RECQL4 gene. In this case, the affected gene is encoded for a helicase. The most common mutation is the nonsense mutation. In between 60 and 65 percent of all patients, defects in the RECQL4 gene are the cause of Rothmund-Thomson syndrome. Both type RTS-1 and RTS-2 are inherited in an autosomal recessive manner.
Symptoms, complaints, and signs
The typical feature of Rothmund-Thomson syndrome is the rash on the face that cannot be overlooked, which is poikiloderma. This rash is the main symptom of the genetic skin disease. Poikiloderma also distinguishes the disease from RAPADILINO syndrome. Other features of Rothmund-Thomson syndrome include sparse scalp hair, frequent absence of eyelashes or eyebrows, short stature, skeletal malformations, juvenile cataracts, and the presence of a radial club hand. Furthermore, affected individuals age prematurely and develop a predisposition to cancer. Symptoms differ between RTS-1 and RTS-2. In RTS-1, poikiloderma, ectodermal dysplasia and juvenile cataracts of the eyes occur. In subtype RTS-2, patients also suffer from poikiloderma. There are also congenital deformities of the bones and an increased risk of osteosarcoma, malignant bone tumors in adolescence. Later in life, skin cancers may also occur. In Rothmund-Thomson syndrome, the skeletal malformations are manifested, among other things, by a saddle nose, a radial club hand or a prominent forehead. In some cases, however, they can be detected only by x-ray.
Diagnosis and course of the disease
Diagnosis must also distinguish between the two forms of Rothmund-Thomson syndrome. For example, no molecular genetic triggers could be found for the development of RTS-1. For this reason, the diagnosis is based on the symptoms present. For this purpose, a special scoring table was created to collect the different symptoms of the disease. With the help of point values, the examining physician can determine whether RTS-1 is present. If RTS-2 is suspected, it is possible to determine the mutation at the RECQL4 gene by performing a genetic test. This usually also detects RTS-2. The presence of Rothmund-Thomson syndrome should be considered if the patients suffer from osteosarcoma.A differential diagnosis must be made to the RAPADILINO syndrome as well as to the Baller-Gerold syndrome, since mutations at the RECQL4 gene are also found in these diseases. Rothmund-Thomson syndrome takes a different course. Thus, despite their visible premature aging process, patients have a relatively normal life expectancy, provided no malignant cancer is present. Some patients have an increased risk of developing secondary malignancies. In these cases, prognosis is determined by the quality of cancer screening and cancer treatment. If osteosarcoma occurs, the 5-year life expectancy for patients is between 60 and 70 percent.
Complications
In Rothmund-Thomson syndrome, affected individuals suffer from a number of different skin complaints. These complaints have a very negative effect on aesthetics, causing many sufferers to feel unwell and suffer from inferiority complexes or lowered self-esteem. Depression or other psychological complaints can also occur as a result. Especially in children, Rothmund-Thomson syndrome can lead to bullying or teasing. Furthermore, short stature and various skeletal malformations also occur. Patients suffer from limitations in movement and, in some cases, the development of bone tumors. Skin cancer can also develop as a result of the disease and possibly significantly reduce the life expectancy of the affected person. Furthermore, in many cases the parents or relatives are also affected by the symptoms of Rothmund-Thomson syndrome and also suffer from psychological complaints. Since there is no causal treatment for the syndrome, only symptomatic treatment can be carried out. This does not lead to complications. However, those affected depend on the transplantation of stem cells to defeat the cancer. A completely positive course of the disease usually cannot be achieved.
When should you see a doctor?
Because Rothmund-Thomson syndrome is a hereditary skin disease with familial prevalence, physician contacts are inevitable early in life. However, the facial poikiloderma associated with the disease does not remain the only symptom that makes life difficult for those affected. People with Rothmund-Thomson syndrome also suffer from orthopedic or ophthalmologic sequelae. Sufferers of both sexes are also more likely to develop cancer. However, the two subtypes of Rothmund-Thomson syndrome occur comparatively rarely. No more than 300-320 cases have been documented throughout the world. Given the rarity of Rothmund-Thomson syndrome, it is comparatively difficult to even find an expert physician who can diagnose Rothmund-Thomson syndrome. Differentiation from other syndromes with similar symptoms is necessary. Medical treatments are essential in most cases, even if there is no cure. Rothmund-Thomson syndrome can only be treated symptomatically. Specialists and medical specialists of different disciplines will strive for a close cooperation. The collaboration of dermatologists, orthopedists, ophthalmologists, surgeons, or oncologists represents the best way to help sufferers achieve a better quality of life.
Treatment and therapy
To date, there is no therapy for the cause of Rothmund-Thomson syndrome. For this reason, treatment is limited to alleviating the symptoms. Because the symptomatology is considered to be exceedingly complex, it is advisable for the patient to receive interdisciplinary treatment. This means that the therapy is carried out by medical professionals from different disciplines. In the case of Rothmund-Thomson syndrome, this includes surgeons, orthopedists, ophthalmologists, oncologists and dermatologists (skin specialists). Part of symptomatic therapy includes annual ophthalmologic examination, treatment of telangieectasia, and radiologic examinations to check for osteosarcoma. A possible novel therapeutic option is stem cell transplantation. It is still in clinical trials and has been performed in only two patients so far. In one patient, an allogeneic transplantation of bone marrow was performed. In the other case, treatment involved the use of umbilical cord blood stem cells.
Prevention
Taking preventive measures against the onset of Rothmund-Thomson syndrome is unfortunately not possible.Thus, the condition is one of the hereditary diseases whose cause is still largely unknown.
Aftercare
Follow-up care for Rothmund-Thomson syndrome depends on the subtype of the disease and its particular course, as well as the treatment measures chosen and the patient’s constitution. In general, follow-up involves review of the various symptoms and discussion of next steps. Surgical intervention often places a considerable burden on patients. During follow-up, the surgical scars are checked to determine the success of the treatment. Furthermore, patients are encouraged to rest. In the case of protracted illnesses, treatment with painkillers may be necessary. In addition, patients sometimes need psychological support. Another component of aftercare is information about advances in new treatment methods, such as stem cell transplantation or bone marrow transplantation, which have been successfully performed on some patients to date. In addition, a routine examination of the various bodily functions that have been affected by the cancer takes place during follow-up care. Provided there are no complications, the patient can then be discharged. Since this is an extremely rare condition that can only be treated symptomatically, the patient is advised to continue close medical monitoring even after recovery. Follow-up care for Rothmund-Thomson syndrome is provided by dermatologists, orthopedists, ophthalmologists, oncologists, or surgeons, depending on the symptoms.
What you can do yourself
Because Rothmund-Thomson syndrome is associated with an increased risk of cancer, affected individuals should examine their bodies independently at regular intervals for irregularities or abnormalities in the skin. In addition to visits to the doctor for medical examinations, it is advisable in everyday life to enlist the help of fellow human beings to check areas that are difficult to access for possible changes in the skin’s appearance. Since the genetic disease already shows abnormalities in the first years of life, the growing child should be informed about the existing disease and its further course at an early stage. In the daily handling of the disorder, it is important to avoid sudden situations and unpleasant surprises. Therefore, the close social environment should also be informed about the existing health impairment. As visual changes occur, strengthening self-confidence is important in the child’s development and growth process. Since surgery is often performed to improve the situation, mental support for the child is just as important as strengthening the immune system. To cope with an operation, the organism needs defensive forces. Mental strength can be built up in cooperation with a psychotherapist. In addition, the therapies offered help to cope well emotionally with the challenges of the disease. In some cases, parents should also consider seeking psychotherapeutic treatment.
