Three mutation-related malformation syndromes are summarized as tricho-rhino-phalangeal dysplasias. The causative mutations affect the TRPS1 gene on the long arm of chromosome 8. Treatment is symptomatic and ideally begins in the form of early support in the first year of life.
What is tricho-rhino-phalangeal dysplasia?
Dysplasias are abnormalities of body parts, organs or tissues. Numerous clinical pictures are associated with dysplasia. This applies in particular to congenital malformation syndromes. Tricho-rhino-phalangeal dysplasia is one of the malformation syndromes. The syndrome is characterized by a combination of facial dysmorphism and cone epiphyses. For food allergy basics, please visit theinternetfaqs.com.
Tricho-rhino-phalangeal dysplasia can be divided into three different types:
- Type I was first described by the German dermatologist Klingmüller in the middle of the 20th century.
- Type II is known as Langer-Giedion syndrome. In the 20th century, Giedion classified the disease as a growth and developmental disorder.
- Type III is called Alè-Calò syndrome and goes back to the Italian first descriptors G. Alè and S. Calò.
The exact prevalence of the congenital disease is not yet known. It is estimated to be a rare disease that runs in families. Inheritance is believed to be autosomal dominant. However, spontaneous new mutations have also been observed in connection with the disease. The exact cause and the clinical picture depend on the type of disease in each individual case.
The cause of tricho-rhino-phalangeal dysplasia is a gene mutation or chromosomal deletion. The long arm of chromosome 8 was identified as the location of the gene mutation. The responsible TRPS1 gene is located on gene locus 8p24.1 of this chromosome. Type I dysplasia occurs with a partial or complete loss of a TRPS11 gene copy. A causal chromosome anomaly that destroys the gene through translocation or inversion is also conceivable.
The most common cause is a point mutation of the gene. The second type of dysplasia is due to a deletion. Those affected are missing a more or less large part of the EXT1 and TRPS1 genes. Other genes are often lost as well. Type II is therefore referred to as gene group syndrome. The third type of tricho-rhino-phalangeal dysplasia is always preceded by a missense mutation in exon six of the TRPS1 gene.
Spontaneous new mutation is the sole primary cause of the deletions. The other two forms of dysplasia can be inherited in an autosomal dominant manner. Inheritance is complete penetrance. Any change in the affected genes leads to a disease.
Symptoms, Ailments & Signs
Cone epiphyses on the middle phalanges are considered characteristic of all types of tricho-rhino-phalangeal dysplasia. This manifestation is associated with a pear-shaped nasal deformity, muscular weakness, and a high philtrum in all subforms of the disease. In addition, thin and sparse hair with often premature alopecia can give a characteristic indication of the group of diseases. Other symptoms differ depending on the type.
In type I, there is also often short stature with a pronounced shortening of the phalanges or metatarsal and metacarpal bones. The picture is rounded off by femoral head changes in this sub-form of the disease. Type II of the disease is characterized by reduced intelligence.
In the first years of life, this subtype often develops exostoses at the long ends of the bones, which are associated with pain and functional limitations. Type III is the most pronounced variant of tricho-rhino-phalangeal dysplasia and is similar to type I in its basic features. However, it is more pronounced in this variant. There is also severe brachydactyly.
Diagnosis & course of disease
The suspected diagnosis of tricho-rhino-phalangeal dysplasia can be made by visual diagnosis. X-ray imaging is used to confirm the diagnosis. X-rays typically show cone epiphyses with extremely short, possibly yellow metacarpal bones. Molecular genetic diagnostics can provide definitive information.
Due to the large number of possible but relatively unspecific symptoms, the diagnosis of tricho-rhino-phalangeal dysplasia often turns out to be a challenge in individual cases. The earliest possible diagnosis has a positive effect on the course of the disease. Treatment should be started as early as possible to ensure a favorable outcome.
The symptoms of this disease can vary greatly. For this reason, the further course of the disease also depends very much on the exact severity of the symptoms. The patients primarily suffer from severe muscle weakness. A deformation of the nose can also occur and have a negative effect on the patient’s aesthetics.
Especially when it comes to children or young people in general, those affected are often bullied or teased. This can also lead to psychological problems or depression. Short stature also occurs, which has a very negative effect on the patient’s quality of life.
In some cases, the disease leads to reduced intelligence, leaving affected people dependent on other people’s help in their lives. Parents or relatives often suffer from psychological problems or depression. Since no causal treatment of this disease is possible, only the individual symptoms can be treated.
There are no further complications. However, complete healing is not achieved. With the help of various therapies, the individual symptoms can be alleviated. The life expectancy of the patient is usually not limited by the disease.
When should you go to the doctor?
Since this disease cannot heal itself and the symptoms caused by the disease can continue to worsen, the affected person should consult a doctor as soon as the first symptoms and signs appear. The sooner a doctor is consulted, the better the further course is, as a rule. A doctor should be contacted if the person concerned suffers from various malformations on the body. A deformed nose in particular indicates the disease. In some cases, the disease also causes severe muscle weakness and very thin and cracked hair.
Reduced intelligence or short stature can also indicate this disease, so that a doctor should be consulted. It is not uncommon for those affected to suffer from severe pain or restricted movement due to the malformations. As a rule, the disease can be diagnosed by a general practitioner or a pediatrician. The treatment then depends on the severity and severity of the symptoms and is usually carried out by a specialist.
Treatment & Therapy
There is no causal therapy for patients with tricho-rhino-phalangeal dysplasia. Treatment is symptomatic and depends on the symptoms in the individual case. The cone epiphyses can be treated, for example, by surgical intervention. Resection arthrodeses with tension band osteosynthesis offer an intervention option. In this way, the patient’s pain is reduced.
Language problems, developmental problems, muscle weakness and cognitive limitations are also addressed in supportive therapy. Speech therapy is available to treat speech problems. Educational games promote the cognitive development of patients and physiotherapy can be used to strengthen muscles. Ideally, the supportive measures are already used in the first year of life in the form of early support.
Drug therapies to prevent infections are conceivable. For example, the administration of infection-inhibiting pediatric Septrin. On the part of dietary therapy, overcaloric food supplements can be used. In order to support parents in particular in dealing with the illness, there are psychotherapeutic measures, educational talks and self-help groups. Gene therapy is currently an important focus in medical research. In the future, tricho-rhino-phalangeal dysplasia may be treatable causally through gene therapy.
Tricho-rhino-phalangeal dysplasias are caused by mutations. It is not yet known which connections lead to the mutations. For this reason, the clinical picture is difficult to prevent. An affected person passes the disease on to their own children with a risk of up to 50 percent. This connection can be considered when planning a family.
Intensive follow-up treatment should always follow the treatment of tricho-rhino-phalangeal dysplasia. The symptoms and complaints remaining after the therapy are decisive here. Those affected should take care of their bones and joints throughout their lives. If pain persists or chronic pain develops over the course of life as a result of permanent deformation of the bones, these must be treated separately.
In addition, all check-ups that are recommended for adults from a certain age group should be carried out early on in people with tricho-rhino-phalangeal dysplasia. This applies in particular to examinations of the skeleton and muscles and the ear, nose and throat area.
Short stature should also be treated by the pediatrician with growth hormones. Parents of a child born with trichorhinophalangeal dysplasia should consider prenatal diagnosis in future pregnancies. The probability of having another child with tricho-rhino-phalangeal dysplasia in these cases is very high and prenatal diagnostics can bring certainty about this.
Despite successful medical treatment, the disease can be accompanied by social and personal problems over the course of life, which put a great strain on the psyche. Therefore, the families of affected persons should offer them the greatest possible emotional stability. If mental illnesses nevertheless occur, they must be treated separately, psychotherapeutically and psychiatrically.
You can do that yourself
Medical treatment is necessary for tricho-rhino-phalangeal dysplasia. The treatment of the various malformations and physical complaints can be supported by the patient with suitable self-help.
External abnormalities such as sparse hair or prominent ears, lips or teeth can be partially treated cosmetically. For example, the sallow skin can be hidden with cosmetics. The typical joint problems require comprehensive physiotherapy. This can be supported by the patients at home with suitable exercises. To avoid respiratory infections, careful attention must be paid to good hygienic conditions. It is also important to avoid other risk factors such as cold or contact with sick people. If there is a heart defect, a pacemaker may have to be used. The patient must strictly adhere to the safety regulations and inform the doctor in the event of any abnormalities.
Many misalignments are treated surgically. Rest and bed rest are important after the procedures. Due to the poor physical condition of most of those affected, there should always be a relative or professional nurse nearby who can contact the emergency doctor in the event of complications. Which measures are necessary in detail for tricho-rhino-phalangeal dysplasia depends on the individual symptoms of the complex disease. Those affected can also find help from self-help groups and the medical emergency service.