Coffin-Siris syndrome is a congenital malformation syndrome with the leading symptom of short stature. The syndrome is caused by a genetic mutation that usually occurs sporadically. Therapy focuses on treating the epilepsy.
What is Coffin-Siris syndrome?
Several subgroups exist 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 disorder that is associated with hypoplasia of the limbs, intelligence impairment, and nail hypoplasia in addition to short stature. The complex of symptoms was first described in 1970 by the US pediatrician G. S. Coffin and the radiologist Ev. Siris, in whose honor the syndrome is named. The incidence for the syndrome is reported to be less than one case in 1,000,000 people. The syndrome has a genetic basis and may be inherited in some circumstances. However, the condition is much more often sporadic and thus unlikely to be associated with familial clustering. If familial clustering exists, the mode of inheritance appears to be autosomal recessive.
Causes
Coffin-Siris syndrome is caused by genetics. More specifically, the complex of symptoms is caused by a genetic mutation, which in most cases corresponds to a new mutation. The disease has mutations at the 7q32-q34 locus as its basis in most patients. In some affected individuals, mutations have also been found in the SOX11 gene, which is located at locus 2p25.2. 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 modify and rearrange the packaging of DNA. When mutations occur in the coding genes, the protein complex loses its physiological shape and thus also part of its function. The exact relationships between the individual symptoms of Coffin-Siris syndrome and the functions of the protein complex have not yet been conclusively clarified.
Symptoms, complaints, and signs
Patients of Coffin-Siris syndrome suffer from a complex of different symptoms. The marked short stature of affected individuals represents the leading symptom. Intrauterine, the first growth retardations occur, which also affect the cranial region. Microcephaly or brachycephaly may develop. In addition, many patients of the syndrome suffer from epilepsy. The body hair of affected individuals is conspicuous. In addition to sparse hair on the infant’s head, hypertrichosis may be present on the back. The same applies to the areas of the upper arm and thigh. Some facial abnormalities are characteristic of Coffin-Siris syndrome. These include bushy brows, epicanthus, and an abnormally narrow palpebral fissure. Infants often squint and also have a broad and unusually short nose. The philtrum is stiffened. In addition, macroglossia is often present. The teeth and enamel are underdeveloped. The ears are often malformed. The phalanges and nails are hypoplastic. Additional symptoms besides clinodactyly may be overmobile joints in the context of hip dislocations, retarded bone age or frequently occurring respiratory infections. Somewhat less commonly, symptoms such as scoliosis or an underdeveloped chest are present.
Diagnosis and course
The physician makes the diagnosis of Coffin-Siris syndrome primarily on the basis of clinical findings. Examinations of genetic material can provide evidence of the typical mutations and thus confirm the diagnosis. Imaging techniques reveal various abnormalities, most notably heterotopia and low gyration. Differentially, Nicolaides-Baraitser syndrome, BOD syndrome, DOOR syndrome, Mabry syndrome, Rubinstein-Taybi syndrome, and Cornelia de Lange syndrome must be excluded. The prognosis for patients depends on the severity of the presentation in each individual case. Aspiration pneumonia, in particular, is a hazard associated with an unfavorable prognosis. Epileptic seizures may also affect prognosis.
When should you see a doctor?
In most cases, Coffin-Siris syndrome results in a marked short stature.This does not require any special diagnosis, and direct treatment is usually not possible either. However, Coffin-Siris syndrome must be monitored by a physician in any case, as it can lead to epileptic seizures. If a seizure should occur, the hospital must be visited or the emergency physician must be called in any case. The earlier the Coffin-Siris syndrome is diagnosed, the higher the chances of a positive course of the disease. In young children, a doctor should already be consulted if they squint or if there are various malformations of the ears. Frequently occurring infections of the respiratory tract can also indicate Coffin-Siris syndrome and should also be examined and treated. As a rule, Coffin-Siris syndrome can be diagnosed by a pediatrician. However, further treatment depends on the severity of the symptoms and is carried out by the relevant specialist.
Complications
Due to Coffin-Siris syndrome, various complications occur throughout life. In most cases, epilepsy is the major complication and is therefore treated first. The affected person suffers from short stature and malformations in the skull area in Coffin-Siris syndrome. Children can become victims of bullying and teasing due to the malformations and growth disorders, which not infrequently leads to psychological problems as well. 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 severe impairment for the affected person. The eyes, ears, and lungs are also affected by Coffin-Siris syndrome and can have malformations. The respiratory tract itself is highly susceptible to infection. Life expectancy is usually reduced by the disease. Treatment for Coffin-Siris syndrome is primarily designed to relieve symptoms and cannot completely cure the disease. Epilepsy and respiratory infections are treated first and foremost so that they do not restrict the patient’s daily life too much. Parents of sufferers are also severely affected by the syndrome and complain of psychological suffering, which can be treated by a psychologist.
Treatment and therapy
Genetic therapies are a current area of research in medicine. To date, however, gene therapy approaches have not reached the clinical phase. Until they reach the clinical phase, genetic diseases remain incurable. Since no causal therapies are currently available, Coffin-Siris syndrome is treated purely symptomatically. Therapy is thus based on the symptoms in each individual case. Above all, the epilepsy must be treated symptomatically. In addition to conservative medicinal procedures, invasive surgical treatment methods are also available for this purpose in some cases. Respiratory infections are usually treated via the administration of antibiotics. The facial abnormalities can be corrected by surgical procedures. In most cases, patients also receive physiotherapy to build up muscles and thus stabilize the overly mobile joints. Early intervention may also be provided to promote normal mental development. Hypoplasias of the phalanges require surgical intervention. Those of the nails can be compensated by transplantation. However, since nail abnormalities are primarily a cosmetic problem, early intervention is usually not essential. Parents of affected children are given instructions to prevent respiratory infections and food aspiration.
Outlook and prognosis
Because Coffin-Siris syndrome is a genetic disorder, it cannot be treated causally. Thus, a complete cure is also not possible for this disease. Only some of the symptoms of the syndrome can be limited, with the epilepsy being treated in the foreground. With proper treatment, the patient does not suffer from a reduced life expectancy. As the affected persons often suffer from respiratory infections, they are significantly limited in their everyday life. Deformities occur on the ears and teeth, which can reduce aesthetics. However, these deformities can be well corrected by surgical interventions. As a rule, strabismus is corrected with glasses.Epilepsy is treated only symptomatically in Coffin-Siris syndrome. Medication can be used to reduce the frequency of epileptic seizures, although it is not possible to predict the next epileptic seizure. Nail discomfort is relieved by transplants, with no further complications or discomfort. Since the breathing difficulties can lead to difficulties in taking food and fluids in childhood, parents are dependent on special therapy for this. These symptoms usually do not recur in adulthood.
Prevention
Coffin-Siris syndrome cannot be actively prevented in the strict sense. Genetic counseling in family planning can possibly prevent a mutation based on familial clustering. However, since the syndrome usually occurs sporadically and the external influencing factors are so far rather unknown, this preventive measure is not considered to be particularly safe. Due to the intrauterine growth disturbances, a diagnosis can possibly already be made by fine ultrasound. To the expectant parents, the malformation ultrasound gives the opportunity to decide against the unborn child.
Follow-up
Follow-up care for Coffin-Siris syndrome is somewhat difficult. Not much can be done about the short stature and all the associated symptoms. Coffin-Siris syndrome is also characterized with other complex complaint patterns such as hypoplasia of the limbs and nails, various dysfunctions, and intelligence reduction. The lack of effective assistance also applies to these. It is possible that Coffin-Siris syndrome may later represent a disease that gene therapy could cure. The many health disorders caused by the genetic defect can at best be treated symptomatically. For example, in the presence of epilespy, a treatment strategy can be chosen that controls the affected individual through close machine monitoring measures. Downstream therapy may need to be adapted to current developments. In addition, physicians and nurses must be careful that patients do not develop pneumonia from accidental inhalation of food particles. It turns out in people with Coffin-Siris syndrome that epileptic seizures as well as aspiration pneumonia and other emergencies can lead to hospitalization. Follow-up care in each case is concerned with working through acute events and continuing treatment according to the situation. The main focus of this disease in the aftercare is also the relief of symptoms. Improving the quality of life should also be a priority in Coffin-Siris syndrome. The life expectancy of affected individuals is diminished given the severity of the genetic defect.
What you can do yourself
Coffin-Siris syndrome is genetic. The patient or family members cannot take steps 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 intervention. Educational and psychological measures can help the child’s intellectual abilities to develop better. If there is no or only a slight intellectual disability, those affected usually suffer greatly from their conspicuous external appearance. Excessive body hair can be removed by means of various cosmetic procedures. Meanwhile, excessively hairy parts of the body can also be permanently epilated by using a laser. Deformities or malocclusions of the teeth also occur frequently. 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. Often, dwarfism is also accompanied by hypermobility of the joints, which can affect the mobility of the patient. In order to prevent or at least mitigate this, physiotherapy should be started at an early stage, which is aimed at stabilizing the affected joints through the targeted development of muscles. Insofar as those affected suffer emotionally from the symptoms of their disease, timely consultation with a psychotherapist is an important step towards self-help.
