Coffin-Lowry syndrome is a malformation syndrome caused by a mutation. The patients’ mutation-defective RSK2 kinase 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 recurrent combinations of various malformations that are present from birth and affect multiple organs or tissues of the body. The group of malformation syndromes includes various disorders caused by either endogenous factors such as mutations or exogenous disorders such as viruses and toxins. Coffin-Lowry syndrome is a symptom complex with a genetic basis that belongs to the malformation syndromes. Affected individuals exhibit physical features such as a widened nose and enlarged lips. The syndrome was first described by the US pediatricians G. S. Coffin and R. B. Lowry. Both described the syndrome independently in the late 1960s and early 1970s. Coffin-Lowry syndrome has an incidence of one case per 50,000 newborns. The male sex is more frequently affected because the genetic cause of the disorder is located on the X chromosome. In most cases, affected girls are asymptomatic carriers.
Causes
The cause of Coffin-Lowry syndrome lies in the genes. Patients with the syndrome have an alteration on the X chromosome, located in gene locus Xp22.2-p22.1. The corresponding gene codes in the DNA for a protein called RPS6KA3 (RSK2). This protein is involved in the formation of neurons as an enzyme kinase. In addition, it plays a role in bone growth and exerts some control over the cell cycle. Certain cell communication signaling pathways are also regulated with the involvement of the enzyme. Due to the mutation at the described gene locus, the protein RSH2 changes its structure and, as a component of the kinase, can thus no longer fulfill its physiological function to the full extent. In particular, 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 mode of inheritance. Coffin-Lowry syndrome can therefore be described as a hereditary disease or inherited disorder. Nonetheless, up to 80 percent of patients in the family are isolated cases.
Symptoms, complaints, and signs
Patients with Coffin-Lowry syndrome suffer from a complex of different symptoms and malformations. Most often, they possess an exceptionally strong forehead and strong eyebrow arches. In addition to a broad nasal bridge, their wide interocular distance is striking. Their eyelid axes often pull downwards and thus assume an antimongoloid position. In addition, the nasal floor is often turned forward. The lips are usually full, with the lower lip appearing inverted. In addition to large and soft hands with loose skin, hyperextensibility of the hand and finger joints characterizes the symptomatology. Many patients have pointed fingers and suffer from progressive kyphoscoliosis, which can affect breathing and cardiac activity. Micrognathia has also been documented as a symptom of the syndrome. Mentally, retardation is often present with varying degrees of severity. The clinical picture is rounded off in individual cases by hearing loss, episodes of falling, epilepsy or extreme sensitivity to touch. In addition to the symptoms mentioned, bone symptoms often occur. Obesity or psychiatric disorders may also occur. Women often remain asymptomatic throughout their lives.
Diagnosis and course
Differentially, the possibility of another malformation syndrome must be considered in addition to Coffin-Lowry syndrome if the presentation is appropriate. These differential diagnoses include fragile X syndrome, Sotos syndrome, and Williams-Beuren syndrome, as well as ATR-X syndrome, in addition to α-thalassemia mental retardation syndrome. Diagnosis is usually guided by the clinical picture, which may be supported by radiological findings such as cranial hyperostosis or an abnormally shaped vertebral body, retarded bone age, or tufted end phalanges. With mutation analysis in the RPS6KA3 gene, confirmation of the diagnosis is possible in a very short time. The prognosis for patients with the syndrome depends on the severity.In most cases, there is an unfavorable prognosis, although this can be improved by regular checkups and early diagnosis.
Complications
Because of Coffin-Lowry syndrome, patients experience a variety of malformations and complications. In most cases, the syndrome is characterized by facial deformities, with the eyebrows in particular arranged in the form of arches. The distance between the eyes is also greater than in people who do not have the disease. Because of this, the patient feels unattractive in many and suffers from decreased self-esteem. The fingers and joints may be hyperextended and the affected person’s skin sits loosely. In some cases, breathing and heart function may also be impaired, making it impossible for the patient to perform physical tasks. Mental disturbance and retardation also develops, so the patient often depends on others for help. Hearing loss can also occur as a complication of Coffin-Lowry syndrome, continuing to complicate the patient’s life. In severe cases, epileptic seizures or mental disorders occur. Treatment of Coffin-Lowry syndrome is aimed only at treating the symptoms themselves; the disease cannot be cured in itself. Due to the syndrome, there is a decreased life expectancy. Usually, treatment is in the form of therapies, so there are no further complications in the process.
When should you go to the doctor?
In most cases, Coffin-Lowry syndrome malformations are detected right after the patient is born, so early treatment can also begin. However, a physician should always be consulted if the child suffers from malformations, especially if they appear later in development. Hyperextensibility of the joints or hands can also indicate Coffin-Lowry syndrome and requires a medical examination. Parents should also seek medical attention if the child suffers from breathing difficulties, as this can also weaken the heart. In many cases, patients also suffer from mental retardation and need special support in life for this reason. The earlier the retardation is detected, the better it can be treated. If an epileptic seizure occurs as a result of Coffin-Lowry syndrome, it must also be treated by an emergency physician. The syndrome is usually diagnosed by a pediatrician or general practitioner. However, further treatments depend greatly on the severity of the symptoms.
Treatment and therapy
For appropriate treatment of Coffin-Lowry syndrome, early diagnosis is critical. Essentially, this early diagnosis has a positive effect on any progressive kyphoscoliosis. The cardiovascular functions of affected individuals can be closely monitored if diagnosed early. The treatment of patients should be understood as symptomatic supportive treatment. A causal treatment to cure the syndrome is not yet available. Eventually, this will change once gene therapy approaches reach the clinical phase. Standard therapies for patients with Coffin-Lowry syndrome currently do not exist, nor do causative therapeutic measures. For example, progressive kyphoscoliosis may require physiotherapy or brace applications, but the likely effectiveness of the various 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. Speech therapy training may also make sense if symptoms such as delayed language acquisition are present. Some of the fascial deformities can be corrected by plastic surgery. However, purely cosmetic defects are negligible as long as malformations that impair bodily function have not been brought under control.
Outlook and prognosis
Because Coffin-Lowry syndrome results in a number of different malformations and deformities due to a genetic defect, they cannot be completely cured or treated causally. Therefore, only symptomatic therapy is available to the affected person, mainly to limit the epilepsy. Hearing loss can usually only be treated by a hearing aid.Should a complete hearing loss occur, it can no longer be treated. The individual deformities can be treated with various exercises from physiotherapy or physiotherapy. In most cases, the affected person can lead an ordinary life without any restrictions. Corset applications can also alleviate the discomfort. Some of the deformities can be treated by surgery if desired. As a rule, no further complications occur. Since most patients are also unable to speak properly due to Coffin-Lowry syndrome, logopedic training is necessary to facilitate the patient’s daily life. If Coffin-Lowry syndrome is not treated, the symptoms will make the patient’s life extremely difficult and may possibly reduce life expectancy. However, a complete cure for the syndrome is not achieved.
Prevention
The only prevention option in the context of Coffin-Lowry syndrome is genetic counseling. For example, in high-risk families with a known mutation, prenatal diagnostics including heterozygote testing can be performed. Genetic counseling should be considered in family planning. The decision not to have a child of one’s own and to adopt may be a conceivable precautionary step for at-risk families.
Follow-up
Patients suffering from Coffin-Lowry syndrome rely on long-term follow-up care. To reduce physical limitations, rehabilitation should begin while the acute symptoms are being treated. In this way, any poor posture and other typical symptoms can be reduced. Physiotherapy is essential for restoring the patient’s motor skills. Affected persons can also exercise themselves, at home and during sports. After surgery, the specialist must check the healing process of the surgical wounds weekly and prescribe painkillers or wound ointments if necessary. Aftercare also includes psychotherapy and drug treatment with painkillers, sedatives and antidepressants. Attention and concentration should also be trained. Despite all the measures, people suffering from Coffin-Lowry syndrome need constant care even after the actual treatment. As a result, psychological complaints often arise, which also need to be treated in the long term. Sufferers need to consult a suitable therapist who can provide the patient with individual counseling. Accompanying discussions with other affected persons are useful. Medical check-ups are an important part of follow-up care and should take place twice a month. Since Coffin-Lowry syndrome can occur in different forms, the individual therapy and aftercare always depends on the patient’s state of health and can vary accordingly.
What you can do yourself
Coffin-Lowry syndrome is genetic. So far, there are neither conventional medical methods nor alternative cures to treat the disease causally. However, it is possible to take action against a number of the symptoms and to better manage the difficulties that sufferers face in coping with their daily lives. Obesity, which is common, can be prevented by eating a healthy, low-fat diet. Patients or their relatives can have a nutrition plan drawn up by an ecotrophologist. This should be started at the first signs of obesity. Many patients also suffer from their often very noticeable external appearance. If it is a matter of isolated anomalies, such as an overly wide nose or greatly enlarged lips, the patient can normalize his or her appearance through cosmetic surgery. If the patient’s problems cannot be corrected by means of plastic surgery, he can learn to cope better with the reactions of third parties to his external appearance within the framework of psychotherapy. In case of speech and movement disorders, a speech therapist and a physiotherapist should be consulted. With consistent training, the patient can usually significantly reduce these symptoms. In the case of impaired learning ability, it is important that the parents of affected children seek appropriate early intervention.
