The Coffin-Lowry syndrome is a malformation syndrome, which is caused by a mutation. The mutation-related defective RSK2 kinase in the patient loses its phosphotransferase activity and is responsible for the multiple malformations. Treatment of patients with the syndrome is purely symptomatic.
What is Coffin-Lowry Syndrome?
Malformation syndromes are recurring combinations of different malformations that are present from birth and affect several organs or tissues of the body. The group of malformation syndromes includes various diseases that are caused either by endogenous factors such as mutations or exogenous disorders such as viruses and toxins.
The Coffin-Lowry syndrome is a symptom complex with a genetic basis that belongs to the malformation syndromes. Those affected have physical characteristics such as a widened nose and enlarged lips. The first description of the syndrome goes back to the US pediatricians GS Coffin and RB Lowry.
Both described the syndrome independently in the late 1960s and early 1970s. Coffin-Lowry syndrome has an incidence of one case in 50,000 newborns. The male sex is more often affected because the genetic cause of the disorder is located on the X chromosome. In most cases, affected girls are asymptomatic carriers.
The cause of Coffin-Lowry syndrome lies in the genes. Patients with the syndrome have a change on the X chromosome, which is located in the gene locus Xp22.2-p22.1. The associated gene encodes a protein called RPS6KA3 (RSK2) in the DNA. This protein is involved in the formation of nerve cells as an enzyme kinase.
It also plays a role in bone growth and has some control over the cell cycle. Certain signal pathways in cell communication are also regulated with the participation of the enzyme. As a result of the mutation on the gene locus described, the RSH2 protein changes its structure and, as a component of the kinase, can no longer fully fulfill its physiological function.
Above all, the defective RSK2 kinase loses its phosphotransferase activity, to which all symptoms of Coffin-Lowry syndrome can be attributed. The mutation is passed on in the X-linked dominant inheritance. Therefore the Coffin-Lowry syndrome can be described as hereditary disease or hereditary disease called. Nonetheless, up to 80 percent of patients in the family are isolated cases.
Symptoms, ailments & signs
Patients with Coffin-Lowry syndrome suffer from a complex of different symptoms and malformations. Most of them have an exceptionally strong forehead and strong eyebrow arches. In addition to a wide bridge of the nose, you will notice a wide eye relief.
Their eyelid axes often pull down and thus assume an antimongoloid position. In addition, the floor of the nose is often facing forward. The lips are usually full, with the lower lip looking everted. In addition to large and soft hands with loose skin, the overstretchability of the wrists and finger joints characterizes the symptoms.
Many patients have pointed fingers and suffer from progressive kyphoscoliosis, which can impair breathing and cardiac activity. Micrognathia has also been documented as a symptom of the syndrome. Mentally, there is often a retardation of varying degrees.
The clinical picture is rounded off in individual cases by hearing loss, episodes of falls, epilepsy or extreme sensitivity to touch. In addition to the symptoms mentioned, there are often bone symptoms. Also, obesity or psychiatric disorders may occur. Women often remain asymptomatic throughout their lives.
Diagnosis & course
In the differential diagnosis, in addition to the Coffin-Lowry syndrome, the possibility of another malformation syndrome must be considered if the patient has a corresponding appearance. These differential diagnoses include the α-thalassemia mental retardation syndrome, the fragile X syndrome, the Sotos syndrome and the Williams-Beuren syndrome as well as the ATR-X syndrome.
The diagnosis is usually based on the clinical picture, which can be supported by radiological findings such as a cranial hyperostosis or an abnormally shaped vertebral body, a retarded bone age or tufted terminal phalanges. With the mutation analysis in the RPS6KA3 gene, the diagnosis can be confirmed in the shortest possible time.
The prognosis for people with the syndrome depends on its severity. In most cases, the prognosis is poor, which can be improved with regular check-ups and an early diagnosis.
Due to the Coffin-Lowry syndrome, various malformations and complications occur in the patient. In most cases, the syndrome is characterized by deformities in the face, with the eyebrows in particular arranged in the form of arches. The distance between the eyes is also greater than in people who are not ill.
Because of this, in many cases the patient feels unattractive and suffers from decreased self-esteem. The fingers and joints can be overstretched and the affected person’s skin is loose. In some cases, breathing and heart function may also be impaired, making it impossible for the patient to perform physical work. Mental disorder and retardation also develop, so that the patient often has to rely on the help of other people.
Hearing impairment can also occur as a complication in Coffin-Lowry syndrome and continue to complicate the patient’s life. In severe cases, epileptic seizures or mental disorders occur. Treatment for Coffin-Lowry syndrome is aimed only at treating the symptoms themselves, the disease itself cannot be cured. The syndrome leads to a reduced life expectancy. As a rule, treatment takes the form of therapies so that there are no further complications.
When should you go to the doctor?
In most cases, the malformations of Coffin-Lowry syndrome are recognized immediately after the patient is born, so that early treatment can also begin. However, a doctor should always be consulted if the child suffers from malformations, especially if these only appear in the further course of development. Overstretchability of the joints or hands can also indicate Coffin-Lowry syndrome and requires a medical examination. Parents should also see a doctor if the child has difficulty breathing, as this can also weaken the heart.
In many cases, the patients also suffer from mental retardation and for this reason require special support in life. The earlier the retardation is recognized, the better it can be treated. If the Coffin-Lowry syndrome leads to an epileptic seizure, this must also be treated by an emergency doctor. The diagnosis of the syndrome is usually made by a pediatrician or a general practitioner. The further treatments, however, depend heavily on the severity of the symptoms.
Treatment & Therapy
Diagnosing Coffin-Lowry syndrome as early as possible is crucial for adequate treatment of Coffin-Lowry syndrome. Essentially, this early diagnosis has a positive effect on possibly progressive kyphoscoliosis. The cardiovascular functions of those affected can be closely monitored if diagnosed early.
The treatment of the patient is to be understood as symptomatic supportive treatment. A causal treatment to cure the syndrome is not yet available. Something about this may change as soon as gene therapy approaches reach the clinical phase. Standard therapies for patients with Coffin-Lowry syndrome currently exist just as little as causal therapy measures.
Progressive kyphoscoliosis can, for example, require physiotherapy or the use of braces, but the likely effectiveness of the different treatment options must be assessed on a case-by-case basis. Since many of the patients suffer from intellectual deficits, early intervention is often offered.
Also logopaedic language training can make sense if symptoms are present, such as delayed language acquisition. Some of the fascial malformations can be corrected with plastic surgery. However, pure blemishes can be neglected as long as malformations that impair bodily function have not been brought under control.
Outlook & forecast
Since a number of different malformations and malformations occur in Coffin-Lowry syndrome due to a genetic defect, these cannot be completely cured and also cannot be treated causally. The person concerned is therefore only offered symptomatic therapy, which is primarily intended to limit epilepsy.
The hearing loss can usually only be treated with a hearing aid. If there is a complete hearing loss, it can no longer be treated. The individual malformations can be treated with various exercises from physiotherapy or physiotherapy. Most of the time, the affected person can lead an ordinary life without any restrictions. Using corsets can also alleviate the symptoms. Some of the malformations can be treated with surgery if desired. Usually there are no further complications.
Since most patients with Coffin-Lowry syndrome cannot speak properly either, speech therapy training is necessary to make everyday life easier for the patient. If the Coffin-Lowry syndrome is not treated, the symptoms make the patient’s life extremely difficult and can possibly also reduce life expectancy. However, a complete cure of the syndrome is not achieved.
The only preventive option in the context of Coffin-Lowry syndrome is genetic counseling. In families at risk with a known mutation, prenatal diagnostics including a heterozygote test can be carried out, for example. Genetic counseling should be considered in family planning. The decision against having their own child and adopting it can be a conceivable precautionary step for families at risk.
Patients with Coffin-Lowry syndrome need long-term follow-up care. In order to reduce the physical limitations, rehabilitation measures should be started while the acute symptoms are being treated. In this way, any bad posture and other typical symptoms can be reduced.
Physiotherapy is essential to restore the patient’s motor skills. Those affected can also practice themselves, at home and during sports. After an operation, the specialist must check the healing process of the surgical wounds on a weekly basis and, if necessary, prescribe painkillers or ointments.
Aftercare also includes psychotherapy and drug treatment with pain relievers, sedatives, and antidepressants. In addition, attention and concentration should be trained. Despite all the measures taken, people with Coffin-Lowry syndrome still need constant care even after the actual treatment. This often leads to psychological complaints that also need long-term treatment.
The sick must consult a suitable therapist who can advise the patient individually. In addition, discussions with other affected persons are useful. The medical check-ups are an important part of the follow-up care and should take place twice a month. Since the Coffin-Lowry syndrome can occur in different forms, the individual therapy and aftercare always depends on the patient’s state of health and can therefore vary widely.
You can do that yourself
Coffin-Lowry syndrome is genetic. So far there are neither conventional medical methods nor alternative healing methods to treat the disease causally. However, it is possible to take action against a range of symptoms and better manage the difficulties people face in managing their daily lives.
The common obesity can be prevented by eating a healthy, low-fat diet. The patients or their relatives can have a nutrition plan drawn up by an ecotrophologist. This should start with the first signs of obesity.
Many patients also suffer from their often very noticeable external appearance. If there are isolated anomalies, such as an excessively wide nose or greatly enlarged lips, the patient can normalize his appearance with cosmetic surgery. If the patient’s problems cannot be solved by means of plastic surgery, he can learn in the context of psychotherapy to cope better with the reactions of third parties to his external appearance.
In the case of language and movement disorders, a speech therapist and a physiotherapist should be consulted. Through consistent training, the patient can usually significantly reduce these symptoms. In the case of a restricted ability to learn, it is important that the parents of affected children provide appropriate early intervention.