Clouston syndrome is a type of ectodermal dysplasia. It is caused by an autosomal dominant inherited mutation. No causative treatment is available.
What is Clouston syndrome?
Dysplasias are malformations in various tissues. The heterogeneous disease group of ectodermal dysplasia includes inherited defects associated with malformations of structures from the outer cotyledon. The outer cotyledon of the embryo is called the ectoderm. At the beginning of embryonic development, all cells of the embryo are omnipotent, meaning that they can develop into any tissue through steps of differentiation. Differentiation of the cells into the three germ layers is an early step in embryonic development and converts the omnipotency of the cells to multipotency. That is, the cells of the cotyledons can become only a certain range of tissues. For example, those of the ectoderm become hair, nails, teeth, and skin, including sweat glands. In ectodermal dysplasia, maldevelopment of the ectodermal cells takes place, resulting in malformations of the aforementioned tissues. One ectodermal dysplasia is Clouston syndrome. The symptom complex is also called hidrotic ectodermal dysplasia or ectodermal dysplasia II. It is a rare and congenital disorder characterized by a triad of nail dystrophy, hair loss, and increased corneal formation on the palms. The prevalence is reported to be one to nine affected individuals per 100,000 people. It was first described in 1929, and Canadian physician H. R. Clouston is considered the first describer.
Causes
Genetic causes underlie Clouston syndrome. Familial clustering has been observed in association with the syndrome. Thus, the complex of symptoms is congenital and is passed in the autosomal dominant mode of inheritance. The cause of multiple dysplasias is a genetic mutation. The localization of the causative mutations has also now been defined. The patients suffer from mutations in the GJB6 gene, which is located at the gene locus 13q12. The affected gene codes in the DNA for the so-called gap junction protein connexin-30, a transmembrane protein that enables the direct exchange of different molecules up to sizes of about one kDa by forming gap junctions between neighboring cells. With a mutation in the GJB6 gene, the protein connexin-30 does not have a normal structure. Thus, it fulfills its tasks only inadequately. The formation of gap junctions is impeded. Gap junctions are pore-forming complexes of proteins that tightly connect cells at their plasma membrane. Connexons usually consist of about six subunits and form a channel between the cells that serves the exchange of ions and substances. Due to the Clouston syndrome mutation, subunits of the connexin-30 proteins are interchanged or absent. Channel formation is problematic because of the defective protein structure, so that mass transfer between adjacent cells of ectodermal tissue is impaired.
Symptoms, complaints, and signs
Patients with Clouston syndrome suffer from marked cornification of the palms. In most cases, callus formation increases with age. The patients’ hair falls out more frequently. Moderate to severe hair loss already occurs in infancy and affects all hairy parts of the body. The main hair is usually sparse and brittle. Multiple nail changes are usually present on the nails of affected individuals, such as dystrophies, paronychia or discoloration. The nail tissue is often thickened and grows slowly. In some cases, the nails also fall off. Although the skin is affected by changes, the sweat glands are fully functional. Sweating is thus possible for the patients to a normal degree. Dental changes are usually not present. The severity of all changes may vary. The symptom triad of nail dystrophy, hair loss and callus formation in the sense of hyperkeratosis of the palms is not completely present in every case. For example, some patients lack palmoplantar hyperkeratosis. However, hair loss and nail changes always occur. There is no impairment in everyday life. The life expectancy of those affected is also not limited.In a consequence of severe hair loss, psychological discomfort sets in as secondary diseases in extreme cases.
Diagnosis and course
The species makes the diagnosis of Clouston syndrome on the basis of clinical symptoms. The disease requires differentiation from other dysplasias of the ectoderm. The diagnosis is usually confirmed by mutation detection by molecular genetic analysis. This detection is also possible prenatally. The prognosis for patients with the syndrome is relatively favorable. Impairments in everyday life are not to be expected.
Complications
As a result of Clouston syndrome, the patient usually suffers from severe hair loss and discomfort of the inner surfaces of the skin. These can present an increased formation of callus, which leads to unpleasant feelings and pain. Hair loss occurs at a young age and usually affects all areas of the body that are usually covered with hair. Likewise, there are often complaints about the nails. These can become discolored or even fall out completely. Due to the symptoms, there are often inferiority complexes or feelings of insecurity in the patient, as the appearance suffers greatly from Clouston syndrome. Children may be teased and bullied as a result of the symptoms. Causal treatment of Clouston syndrome is not possible. For this reason, only the symptoms are treated. The patient and parents receive psychological support and counseling to prevent depression and other psychological symptoms. The complications on the skin can possibly be eliminated with the help of ointments, although there is no promise of success for this treatment. Life expectancy is not reduced by Clouston syndrome, but daily life is greatly complicated for the patient.
When should you see a doctor?
In Clouston syndrome, a doctor should be consulted when the patient experiences various skin complaints. In most cases, affected individuals suffer from keratinization disorder, which mainly affects the inner surfaces of the hands. Furthermore, hair loss can also indicate Clouston syndrome and should therefore be investigated. In this case, the hair falls out in different parts of the body. Aesthetic complaints can lead to bullying or teasing, especially in children, so it is advisable to consult a psychologist in case of psychological problems. A medical professional should also be contacted if the nails fall out or break. As a rule, in the case of Clouston syndrome, the dermatologist should be consulted. This person can diagnose the syndrome and also initiate treatment. The life expectancy of the affected person is not reduced and in most cases there is also a positive course of the disease. Severe psychological symptoms should also be treated to avoid further complications or depression. Especially in children, early therapy is necessary in this case.
Treatment and therapy
Patients with Clouston syndrome cannot be cured. Because a mutation underlies the changes, causal therapeutic steps are not available until gene therapy approaches reach the clinical phase. For this reason, only supportive symptomatic treatment can be given to those affected. The individual symptoms can possibly be alleviated by administering medication. In extreme cases, those affected receive psychotherapeutic care. Especially during puberty, severe hair loss can cause psychological discomfort. In supportive psychotherapy, patients can work through insecurities so that a psychologically normal development is guaranteed. Symptoms such as the nail changes and callus formation can be addressed with podological and cosmetic treatments. Ointment dressings may be required for some nail changes. An established therapy for the symptoms does not yet exist, which means that the physician may proceed differently from case to case or try a wide variety of therapeutic approaches. Thus, a more or less long period of time may pass until a suitable and successful therapy is found for the individual case.
Outlook and prognosis
Clouston syndrome cannot be treated causally because it is a genetic disorder. For this reason, there can be no complete cure for the syndrome, although some symptoms can be relieved.Without treatment, patients suffer from hair loss or a significantly increased formation of cornea. Psychological complaints can also occur as a result of these aesthetic symptoms. Furthermore, the disease leads to changes in the teeth and nails. If these are also not treated, severe pain or limitations in everyday life may occur. The symptoms usually worsen over time if no treatment is initiated. Since a causal therapy is not possible, only the symptoms of Clouston syndrome are treated. With the help of surgical interventions, many of the aesthetic complaints can be alleviated. In most cases, patients also require several interventions. Especially teeth and nails have to be treated at an early stage to avoid complications in the patient’s adulthood. The syndrome does not negatively affect the life expectancy of the affected person, although the complaints can occur throughout life.
Prevention
To date, Clouston syndrome can only be prevented through genetic counseling during the family planning phase.
Follow-up care
Because Clouston syndrome is a genetic disorder that cannot be treated causally or completely, there are no direct options for follow-up care. The individual symptoms can be treated by various therapies, but the patient is dependent on lifelong treatment. In order to limit the symptoms as much as possible, regular visits to the doctor and various check-ups are therefore necessary. It may also be possible to try different therapeutic approaches, since Clouston syndrome has not yet been extensively researched. In many cases, Clouston’s syndrome also leads to psychological complaints in those affected, which should be treated by a psychologist. Parents and relatives can also seek psychological treatment in order to avoid complications or psychological upsets. Psychological treatment should be initiated at a young age, as Clouston syndrome often leads to bullying or teasing among children. Although the syndrome does not have a negative effect on life expectancy itself, it does significantly reduce the quality of life. Contact with others affected by the syndrome may eventually have a positive effect on the course and may reveal new therapeutic approaches.
What you can do yourself
Clouston syndrome requires a medical diagnosis. The treatment options available depend on the extent to which the disease occurs and the concomitant symptoms observed. Complaints such as the typical nail changes and callus formation can be counteracted with the help of cosmetic and podological remedies. For nail changes, dressings with medicinal ointments or natural remedies such as arnica or aloe vera are suitable. Pain can also be countered with both classic medicines and natural remedies. Turmeric and St. John’s wort, for example, which can be applied in the form of ointments or tinctures, have proven effective. Hair loss can be countered with appropriate care products. In severe cases, wearing a toupee or medical hair transplantation is useful. In the case of severe skin changes or excessive hair loss, as occurs with the disease, especially during puberty, therapeutic counseling is sometimes advisable. Affected individuals sometimes suffer greatly from Clouston syndrome and the social exclusion associated with it. Therefore, comprehensive medical counseling and support from friends and family members are considered the most important measures.
