Costello syndrome is an autosomal-dominant inherited defect. Characteristic features include developmental delays, mental retardation, cardiac abnormalities, and coarse facial features.
What is Costello syndrome?
Costello syndrome is caused by a mutation in the gene HRAS. The gene defect is inherited in an autosomal dominant manner, which means only one copy of the defective gene is needed to pass on the disease. The genetic defect is inherited by only one parent. Affected children suffer from severe postnatal developmental delay, structural heart defects. But also unusually flexible joints, a large facies, and soft and excess skin with pronounced plantar and palmar furrows at the ulnar finger base joints. There is a predisposition to tumor formation due to excessive cell growth. Costello syndrome is rarely seen, with approximately 150 cases documented worldwide.
Causes
Costello syndrome results from a mutation of the HRAS gene, which plays an important role in growth and mental development. This gene is classified in the group of monomeric GTPases (proteins) that act as molecular switches in cells. The HRAS gene produces proteins that lead to mutation of cells, which can cause malignant or benign tumors. So far, it has not been conclusively determined how this malformation syndrome develops. Characteristics include short stature, mental retardation, dermatologic, craniofacial, cardiac, and external abnormalities. Due to autosomal dominant inheritance, most of the disorders are new mutations that do not persist in a new pregnancy. The complex clinical picture with chronic course is associated with disability and limited life expectancy. There are children who live quite well with their disease and show only a developmental delay without physical limitations. The severe cases are associated with physical illnesses such as structural heart defects and mental retardation. Oxygen deficiency is often present. Many of the affected children cannot eat or swallow, so artificial feeding is indicated. Often, the final diagnosis is made only after many examinations and multiple surgical procedures that place undue stress on the child.
Symptoms, complaints, and signs
Children with Costello syndrome show noticeable developmental delays, underdevelopment, heart defects, coarse facial features, and various skin abnormalities. The developmental delays lead to short stature, and in later life, affected individuals often record abnormal weight gain. Many of the young patients suffer from cardiomyopathy, although other internal organs are less commonly affected. The maldevelopment syndrome is accompanied by a mental developmental delay with an affable and friendly character. Often there is hyperextension of the fingers and malposition of the feet. Dermatologically conspicuous are excess skin areas on the hands, feet and neck. The young patients have an increased tendency to tumor formation, especially rhabdomyosarcoma (soft tissue tumor). Costello syndrome is further accompanied by cardiac abnormalities such as hypertrophic cardiomyopathy (heart muscle disease) and increased heart rate (tachycardia). The growth of Costello children may be completely normal during the first few years of life, with a delay occurring later. Due to a deficiency of crucial growth hormones, patients record a shortened stature. This complex clinical picture causes a difficult diagnostic situation.
Diagnosis
In rare diseases with complex malformations, an exchange of the treating physician with experts is inevitable. The possibility of interdisciplinary cooperation is important to make a final diagnosis. The affected children need support in all areas of the disease; only in this way is it possible 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 remedial 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 professionals.Many physicians reach their limits in this respect and complain about a lack of networking between specialists, therapists, pediatricians in private practice and clinics, which would enable a faster diagnosis. In addition to pediatricians and therapists, the use of developmental neurologists and pediatric cardiologists is indispensable. Diagnosis is based on clinical findings, with papillomas as the characteristic feature. A coarse facie and hyperpigmented skin allow early identification of Costello syndrome. With a differential diagnosis, the physicians clarify whether cardio-facio-cutaneous syndrome or Noonan syndrome may be present. If the findings rule out these conditions, a cardiologic examination is performed to determine possible cardiac involvement.
When should you see a doctor?
Treatment should be initiated early in Costello syndrome. The earlier treatment begins, the higher the affected person’s quality of life may become later in adulthood. As a rule, a doctor should then be consulted if the patient suffers from severe short stature and also obesity. Also, a delay in the overall development usually indicates Costello syndrome and must be examined. In this case, the child’s mental development must also be supported so that complications do not arise in adulthood. Since Costello syndrome can often lead to heart disease, patients are dependent on regular examinations to increase their life expectancy. In most cases, the diagnosis can be made after birth. A pediatrician can also diagnose Costello syndrome and initiate treatment. In many cases, however, the support of other specialists is needed. Furthermore, psychological treatment should also take place if the parents or relatives suffer from psychological complaints or depression.
Treatment and therapy
Individual therapy options do not yet exist, since Costello syndrome has hardly been researched and rarely appears worldwide. Within certain limits, the individual symptoms can be treated with medication to alleviate the symptoms. However, there is no cure for this malformation syndrome. The accompanying structural heart abnormalities can be alleviated with cardiac medications. Children with valvular pulmonary stenosis suffer decreased blood flow and may develop subcutaneous bacterial endocarditis. They are given prophylactic antibiotics to prevent infection of the inner layer of the heart. Dermatologic abnormalities can be treated on an individual basis. Growth retardation and mental retardation are irreversible.
Outlook and prognosis
Because Costello syndrome is inherited through a genetic malformation, no causative treatment is possible in this case. Affected individuals are therefore always dependent on symptomatic therapy, which can only limit the individual symptoms. 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. Skin complaints can also often be limited. However, in the case of mental retardation and delays in growth and development, no treatment can be given, so that the patients are severely limited in their lives and thus usually dependent on outside help in their daily lives. If Costello syndrome is not treated, it usually leads to the death of the affected person, since the malformations of the heart are not corrected. Self-healing does not occur in this case. Whether life expectancy is reduced even with treatment cannot be generally predicted. Often, Costello syndrome also leads to severe psychological discomfort, which can occur not only in the patient but also in the parents or relatives.
Prevention
Medical care for patients is very limited for economic and structural reasons, as the large pharmaceutical companies have no interest in further research. The target group for appropriate drugs is too small and a profit margin is not available. For these economic reasons, improved therapeutic options are hardly in sight. Since it is a genetic disease, prevention is not possible.If this complex malformation syndrome is diagnosed during pregnancy, medical professionals can only adapt their medical care to this new situation. Only with individualized therapy and an ideal social environment are Costello children able to learn mental and physical activities that healthy people take for granted.
Here’s what you can do yourself
Individuals who have Costello syndrome initially require medical treatment. Medical therapy can possibly be supported by various measures and remedies from nature. First and foremost, good observation of the affected child is important. Parents should watch for unusual symptoms and, if in doubt, take the child to a pediatrician. Medicinal treatment is best supported by rest and bed warmth. Infants in particular are often sensitive to prescribed medications and need adequate sleep after taking the drugs. Since growth retardation is irreversible despite all measures, parents must seek professional help in the long term. The child needs a caregiver and, later in life, a trained professional who can monitor the child and take the necessary steps in case of incidents. In case of dermatological abnormalities, the classic home remedies will help, i.e. increased personal hygiene, soothing baths and possibly lotions made from natural remedies. To avoid problems, the use of these remedies should first be discussed with the doctor. In addition, control examinations by the physician are always indicated. Good medical care is especially important in the first months and years of life, since the greatest growth disorders and malformations can occur during this period.
