Diseases

Coffin Siris Syndrome – Causes, Symptoms & Treatment

Coffin-Siris-Syndrom

The Coffin-Siris syndrome is a congenital malformation syndrome with the main symptom of short stature. The syndrome is caused by a genetic mutation that usually occurs sporadically. The focus of therapy is on treating epilepsy.

What is Coffin Siris Syndrome?

There are various subgroups of the so-called malformation syndromes. For example, some malformation syndromes are predominantly associated with short stature . Coffin-Siris syndrome belongs to this subgroup. This is a congenital disease that, in addition to short stature , is associated with hypoplasia of the limbs, intellectual disability and nail hypoplasia .

The complex of symptoms was first described in 1970. The American pediatrician GS Coffin and the radiologist Ev. Siris, in whose honor the syndrome is named. The frequency for the syndrome is reported to be less than 1 case in 1,000,000 people.

The syndrome has a genetic basis and can sometimes be inherited. However, the disease occurs sporadically much more often and is therefore hardly associated with familial accumulation. If there is familial aggregation, the inheritance is apparently autosomal recessive .

causes

Coffin-Siris Syndrome is genetic. More precisely, the complex of symptoms is caused by a genetic mutation , which in most cases corresponds to a new mutation. The disease is based on mutations at the 7q32-q34 locus in most patients.

Mutations in the SOX11 gene, located at locus 2p25.2, have also been found in some affected individuals. In addition, mutations in the ARID1A gene, ARID1B gene, SMARCA4 gene, SMARCB1 gene, and SMARCE1 gene are associated with the disease. These genes code for the individual units of the so-called SWI/SNF chromatin remodeling complex. This complex corresponds to a group of proteins that alter and rearrange the packaging of DNA.

In the case of mutations in the coding genes, the protein complex loses its physiological shape and thus part of its function. The exact connections between the individual symptoms of Coffin-Siris Syndrome and the functions of the protein complex have not yet been conclusively clarified.

Symptoms, Ailments & Signs

Coffin-Siris syndrome patients suffer from a complex of different symptoms. The pronounced short stature of those affected is the main symptom. The first signs of growth retardation, which also affect the skull area, already occur intrauterine. Microcephaly or brachycephaly can develop.

In addition, many patients of the syndrome suffer from epilepsy . The body hair of those affected is conspicuous. In addition to sparse hair on the infant’s head, hypertrichosis may be present on the back. The same goes for the upper arm and thigh areas. Some facial abnormalities are characteristic of Coffin-Siris syndrome.

These include bushy brows, the epicanthus and an abnormally narrow eyelid fissure. The infants often squint and also have a wide and unusually short nose. The philtrum has passed. In addition, macroglossia is often present. Teeth and enamel are underdeveloped. There are often deformities in the ears .

The phalanges as well as the nails are hypoplastic. In addition to clinodactyly, additional symptoms can include overly mobile joints in the context of hip dislocations , retarded bone age or frequent respiratory infections . Symptoms such as scoliosis or an underdeveloped breast are somewhat less common.

Diagnosis & History

The doctor makes the diagnosis of Coffin-Siris syndrome primarily on the basis of the clinical findings. Examinations of the genetic material can provide evidence of the typical mutations and thus secure the diagnosis. Imaging methods show various abnormalities, especially heterotopias and a slight gyration.

Nicolaides-Baraitser syndrome, BOD syndrome, DOOR syndrome , Mabry syndrome, Rubinstein-Taybi syndrome and Cornelia de Lange syndrome must be excluded in the differential diagnosis. The prognosis for the patient depends on the severity of the manifestation in the individual case.

Above all , aspiration pneumonia is a danger that is associated with an unfavorable prognosis. Epileptic seizures can also affect the prognosis.

When should you go to the doctor?

In most cases, the Coffin-Siris syndrome leads to a clearly pronounced short stature. This does not require any special diagnosis, and direct treatment is usually not possible.

However, Coffin-Siris Syndrome must be monitored by a doctor in any case, as it can lead to epileptic seizures. In the event of an attack, you must go to the hospital or call an ambulance . The earlier the coffin-siris syndrome is diagnosed, the higher the chances of a positive course of the disease.

In the case of small children, a doctor should be consulted if they squint or if there are various malformations in the ears. Frequently occurring infections of the respiratory tract can also indicate the coffin-siris syndrome and should also be examined and treated. Coffin-Siris syndrome can usually be diagnosed by a pediatrician. However, further treatment depends on the severity of the symptoms and is carried out by the respective specialist.

complications

Coffin-Siris Syndrome causes various complications that can occur over the course of life. In most cases, epilepsy is the greatest complication and is therefore treated first. In Coffin-Siris syndrome, the person affected suffers from short stature and malformations in the area of ​​the skull.

Due to the malformations and growth disorders, children can become victims of bullying and teasing, which often leads to psychological problems. As a rule, almost all patients with Coffin-Siris syndrome are affected by epileptic seizures. In the worst case, these can lead to death and represent a very strong impairment for the person concerned.

Eyes, ears and lungs are also affected by Coffin-Siris Syndrome and can show malformations. The respiratory tract itself is highly susceptible to infections. Life expectancy is usually reduced by the disease. Treatment for Coffin Siris Syndrome is primarily aimed at relieving symptoms and cannot completely cure the disease.

First and foremost, epilepsy and infections of the respiratory tract are treated so that they do not restrict the patient’s everyday life too much. The parents of those affected are also severely affected by the syndrome and complain about mental illnesses that can be treated by a psychologist.

Treatment & Therapy

Genetic therapies are a current research topic in medicine. So far, however, the approaches to gene therapy have not reached the clinical phase. Until they are in the clinical phase, genetic diseases remain incurable. Since no causal therapies are currently available, the Coffin-Siris syndrome is treated purely symptomatically.

The therapy depends on the symptoms in the individual case. Epilepsy in particular must be treated symptomatically. In addition to conservative medical procedures, invasive surgical treatment options are also available in some cases. Respiratory infections are usually treated with antibiotics .

The facial abnormalities can be corrected by surgical intervention. In most cases, the patients also receive physiotherapeutic care in order to build up muscles and thus stabilize the hypermobile joints. Early intervention can also be used to promote normal mental development. Phalangeal hypoplasia requires surgical intervention.

Those of the nails can be compensated by a transplant. However, since the nail abnormalities are primarily a cosmetic problem, early intervention is usually not absolutely necessary. Parents of affected children receive guidance on how to prevent respiratory infections and food aspiration.

Outlook & Forecast

Since Coffin Siris Syndrome is a genetic disease, it cannot be treated causally. Even a complete cure is not possible with this disease. Only a few symptoms of the syndrome can be limited, with epilepsy being treated in the foreground. With proper treatment, the patient’s life expectancy is not reduced.

Since those affected often suffer from infections of the respiratory tract, they are significantly restricted in their everyday life. Deformities appear on the ears and teeth, which can reduce aesthetics. However, these malformations can be easily corrected by surgical intervention. Squinting is usually corrected with glasses.

Epilepsy is only treated symptomatically in Coffin-Siris syndrome. The frequency of epileptic seizures can be reduced with the help of medication, although it is not possible to predict the next epileptic seizure. Nail ailments are relieved by transplants with no further complications or discomfort. Since the breathing difficulties can lead to difficulties in taking food and liquids in childhood, the parents are dependent on special therapy. In adulthood, these symptoms usually no longer occur.

prevention

Coffin-Siris Syndrome cannot actually be actively prevented. Genetic counseling in family planning can possibly prevent a mutation based on familial accumulation. However, since the syndrome usually occurs sporadically and the external influencing factors are still relatively unknown, this preventive measure is not considered to be particularly safe.

Due to the intrauterine growth disorders, a diagnosis can possibly be made by fine ultrasound. The deformity ultrasound gives expectant parents the opportunity to decide against the unborn child.

aftercare

Follow-up care for Coffin-Siris Syndrome is somewhat difficult. Not much can be done against short stature and all the symptoms that accompany it. Coffin-Siris syndrome is also characterized by other complex symptoms such as hypoplasia of the limbs and nails, various malfunctions and intellectual disability.

The lack of effective support also applies to them. Coffin-Siris syndrome may later represent a disease that gene therapy could cure. At best, the many health disorders caused by the genetic defect can be treated symptomatically.

For example, if epilepsy is present, a treatment strategy can be selected that monitors those affected by close monitoring measures. Subsequent therapy may have to be adapted to current developments. In addition, doctors and nurses must be careful that patients do not contract pneumonia through accidental inhalation of food components.

Evidence shows that epileptic seizures as well as aspiration pneumonia and other emergencies can lead to hospitalizations in people with Coffin-Siris syndrome. The follow-up care deals with the processing of acute events and the further treatment according to the situation.

The focus of this disease is also in the follow-up care to alleviate the symptoms. Improving the quality of life should also be a priority in coffin-siris syndrome. The life expectancy of those affected is reduced given the severity of the genetic defect.

You can do that yourself

Coffin-Siris Syndrome is genetic. The patient or his relatives cannot take any measures to treat the disorder causally. However, self-help measures can be taken against some of the symptoms.

If the typical short stature is accompanied by mental retardation, parents must ensure that their child receives optimal early support. Pedagogical and psychological measures can contribute to the better development of the child’s intellectual abilities.

If there is no or only a slight mental disability, those affected usually suffer greatly from their conspicuous external appearance. Excessive body hair can be removed using a variety of cosmetic procedures. In the meantime, overly hairy parts of the body can also be permanently epilated using a laser.

Malformations or misalignments of the teeth are also common. In these cases, a dentist specializing in aesthetic treatments should be consulted at an early stage . The frequently observed malformation of the nails can be corrected with the help of plastic surgery .

Short stature is often accompanied by hypermobility of the joints, which can impair the patient’s mobility. In order to prevent or at least mitigate this, physiotherapy should be started early on, which is aimed at stabilizing the affected joints through the targeted build-up of muscles.

If those affected are mentally suffering from the symptoms of their illness, timely consultation with a psychotherapist is an important step towards self-help.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.