The Costello syndrome is an autosomal dominant inherited undesirable development. Characteristic features are developmental delays, intellectual disability, cardiac abnormalities, and gross facial features.
What is Costello Syndrome?
Costello syndrome is caused by a mutation in the HRAS gene. The genetic defect is inherited as an autosomal dominant trait, which means that only one copy of the defective gene is necessary for the disease to be passed on. The genetic defect is inherited from only one parent. The affected children suffer from serious postnatal developmental delays and structural heart defects.
But also unusually flexible joints, a large face, as well as soft and excess skin with pronounced plantar and palmar furrows on the ulnar metatarsophalangeal joints. Due to excessive cell growth, there is a predisposition to tumor formation. Costello syndrome appears only rarely, around 150 diseases have been documented worldwide.
Costello syndrome is caused by a mutation in the HRAS gene, which plays an important role in growth and mental development. This gene belongs to the group of monomeric GTPases (proteins) that act as molecular switches in cells. The HRAS gene produces proteins that cause cells to mutate that can cause malignant or benign tumors.
So far it has not yet been conclusively determined how this malformation syndrome develops. Characteristic are short stature, mental retardation, dermatological, craniofacial, cardiological and external abnormalities. Due to the autosomal dominant inheritance, most diseases are new mutations that do not exist in the event of a new pregnancy.
The complex clinical picture with a chronic course is associated with disability and limited life expectancy. There are children who live quite well with their illness and only show a developmental delay without physical limitations. The severe cases are associated with physical illnesses such as structural heart defects and intellectual disability.
Often there is a lack of oxygen. Many of the affected children cannot eat and swallow, which is why artificial feeding is indicated. Often the final diagnosis is only made after many examinations and several surgical interventions that place excessive stress on the child.
Symptoms, ailments & signs
Children with Costello syndrome show noticeable developmental delays, inadequate giftedness, heart defects, rough facial features and various skin anomalies. The developmental delays lead to short stature; in later years of life, those affected often experience noticeable weight gain.
Many of the small patients suffer from cardiomyopathy, but other internal organs are less affected. The undesirable development syndrome is accompanied by a mental development delay with a sociable and friendly character. Often the fingers are overstretched and the feet are misaligned. Excess skin on hands, feet and neck are dermatologically noticeable. The small patients have an increased tendency to develop tumors, especially rhabdomyosarcoma (soft tissue tumor).
Costello syndrome is also accompanied by cardiac abnormalities such as hypertrophic cardiomyopathy (heart muscle disease) and increased heart rate (tachycardia). Costello children’s growth can be completely normal in the first few years of life, with a delay later. Due to a lack of vital growth hormones, patients experience a shortened stature. This complex clinical picture makes it difficult to diagnose.
In the case of rare diseases with complex malformations, an exchange between the treating doctor and experts is essential. The possibility of interdisciplinary cooperation is important in order to make a final diagnosis. The affected children need support in all areas of the disease, this is the only way to improve their quality of life at least to some extent.
Treatment options include physiotherapy to support general and fine motor skills, as well as speech therapy and curative education for general support in the areas of language and independence. The challenge of accompanying children with Costello syndrome on their journey through life can only be met with optimal coordination of all specialists.
Many medical professionals reach their limits in this regard and criticize the lack of a network of specialists, therapists, resident paediatricians and clinics, which would enable a faster diagnosis. In addition to paediatricians and therapists, the use of developmental neurologists and pediatric cardiologists is essential.
Diagnosis is based on clinical findings, with papillomas being the characteristic feature. A rough face and hyperpigmented skin allow an early diagnosis of Costello’s syndrome. With a differential diagnosis, the doctors clarify whether the cardio-facio-cutaneous syndrome or Noonan’s syndrome may be present. If the findings rule out these diseases, a cardiological examination is carried out to determine whether the heart may be involved.
When should you go to the doctor?
Treatment should be started early for Costello syndrome. The earlier treatment begins, the higher the quality of life of the person affected in adulthood can become. As a rule, a doctor should be consulted if the patient suffers from severe short stature and also from obesity. A delay in overall development also usually points to Costello syndrome and needs to be investigated. The mental development of the child must also be supported here so that complications do not arise in adulthood.
Since Costello syndrome can often lead to diseases of the heart, patients depend on regular examinations in order to increase life expectancy. Most of the time, the diagnosis can be made after birth. A pediatrician can diagnose Costello syndrome and initiate treatment. In many cases, however, the support of other specialists is also required. Furthermore, psychological treatment should also take place if the parents or relatives suffer from psychological complaints or depression.
Treatment & Therapy
There are currently no individual therapy options, as Costello syndrome has hardly been researched and only rarely appears worldwide. Within certain limits, the individual symptoms must be treated with medication in order to alleviate the symptoms. However, this malformation syndrome is not curable. The accompanying structural heart abnormalities can be mitigated with heart medication.
Children with heart valve pulmonary stenosis suffer from decreased blood flow and can develop subcutaneous bacterial endocarditis. You will be given prophylactic antibiotics to prevent infection of the inner layer of the heart. Dermatological abnormalities can be treated individually. The growth retardation and mental retardation are irreversible.
Outlook & forecast
Since Costello syndrome is inherited through a genetic malformation, no causal treatment is possible. Those affected are therefore always dependent on symptomatic therapy, which can only limit the individual complaints. A complete cure is therefore not achieved in Costello syndrome.
The individual complaints can be treated with the help of medication, but in many cases surgical interventions are also necessary. The discomfort on the skin can also often be limited. In the case of mental retardation and the delays in growth and development, however, no treatment can take place, so that the patients are severely restricted in their lives and are therefore usually dependent on outside help in their everyday lives.
If Costello’s syndrome is not treated, it usually leads to death, as the deformities in the heart are not corrected. Self-healing does not occur here. It is not generally possible to predict whether life expectancy will also be reduced with treatment. Often the Costello syndrome also leads to severe psychological complaints, which can occur not only in the patient, but also in the parents or relatives.
Medical care for patients is only possible to a very limited extent for economic and structural reasons, as the large pharmaceutical companies are not interested in further research. The target group for appropriate drugs is too small and there is no profit margin. For these economic reasons, there are hardly any prospects of improved therapeutic options.
Since it is a genetic disease, prevention is not possible. If this complex malformation syndrome is diagnosed during pregnancy, doctors can only adapt their medical care to this new situation. Only with individual therapy and an ideal social environment are Costello children able to learn mental and physical activities that are a matter of course for healthy people.
You can do that yourself
People who have Costello syndrome must first seek medical attention. Under certain circumstances, medical therapy can be supported by various measures and means from nature.
First and foremost, it is important to observe the affected child closely. Parents should look out for any unusual symptoms and, if in doubt, take the child to a pediatrician. The drug treatment is best supported by rest and bed warmth.
Small children in particular are often sensitive to the prescribed medication and need sufficient sleep after taking the medication. Since the growth retardation is irreversible in spite of all measures, the parents must seek professional help in the long term. The child needs a carer and, in later life, a trained professional who can monitor the child and take the necessary steps in the event of an incident.
The classic home remedies help with dermatological abnormalities, i.e. increased personal hygiene, soothing baths and possibly also lotions made from natural products. To avoid problems, the use of these agents should first be discussed with the doctor. In addition, check-ups by the doctor are always indicated. Good medical care is particularly important in the first few months and years of life, as this is the period during which the greatest growth disorders and malformations can occur.