Costello syndrome: what is it, symptoms (photo), treatment, prognosis

What is Costello Syndrome?

Costello syndrome is an extremely rare disease that affects various organ systems in the body. This condition is characterized by stunted growth after birth; loose skin on the neck, palms, fingers and feet; noncancerous tumors (papillomas) around the face and anus; developmental delay and mental retardation; and the characteristic appearance of the face.

Other physical features may include the development of dry, rough skin on the palms and soles of the feet (palmoplantar hyperkeratosis), abnormally deep folds in the palms and soles, and / or abnormally flexible finger joints (hyperextended). There is an increase in the incidence of congenital heart disease and a thickening of the heart muscle called cardiomyopathy. Characteristic craniofacial features may include an abnormally large head (macrocephaly); rough facial features; unusually thick lips; and / or abnormally wide nostrils. Affected people have an increased lifetime risk of developing specific cancers.

Costello syndrome is an autosomal dominant genetic condition caused by mutations in the gene HRAS.

Signs and symptoms

Babies with Costello Syndrome are usually of normal birth weight but show poor ability suck, have difficulty swallowing, and are unable to grow and gain weight at the expected rate (inability develop). Stunted growth after birth usually results in short stature during childhood and adulthood. Affected children may have developmental delays or mild to moderate mental retardation. In some people, speech development and / or the ability to walk is significantly delayed. Children with Costello syndrome are usually warm, outgoing personalities.

People with the condition usually have loose skin on their neck, palms, fingers, and soles. The skin in these areas has no elasticity and hangs freely. In addition, the skin may appear wrinkled and thickened. In some cases, certain areas of the skin may become unusually dark (hyperpigmentation). In addition, most people with this condition develop dry, hardened patches of skin (hyperkeratosis) with unusually deep folds in the palms and soles.

Some victims may also have skeletal abnormalities such as dislocated hips, abnormally flexible (overly stretched) finger joints, wrists bent towards the little finger (elbow deviation) and / or unusual pinching of the fibrous cords at the back of the heels (Achilles tendon). Additional skeletal abnormalities include side-to-side curvature of the spine (scoliosis), curvature of the spine from front to back (kyphosis) and reduced range of motion in the shoulders and elbows.

Children with Costello syndrome usually suffer from papillomas around the mouth and nostrils. Papillomas can develop as early as 2 years of age or later. In some cases, these verrucous lesions can be found near the anus. Papillomas usually become more pronounced with age. Other benign tumors have also been reported.

Patients with Costello syndrome have a characteristic appearance. Facial features may include:

• an abnormally large head (macrocephaly);
• low set large thick ears;
• unusually thick lips;
• large, depressed nasal bridge;
• abnormally wide nostrils;
• rough appearance of the face.

In addition, sick children may have unusually curly hair and / or sparse, fine hair on the scalp. Some children develop skin folds at the inner corners of the eyes.

In early childhood, the relative overgrowth of the hindbrain compared to the space available in the posterior fossa of the cranial cavity can lead to crowding and neurological problems.

Vision changes are common and include nystagmus (rapid eye movements) and strabismus in young patients, and rarely in the elderly keratoconus (abnormal thickening of the cornea).

Children with Costello syndrome often have certain heart abnormalities. They can include:

• structural heart defects that are present at birth (congenital heart defects);
• abnormal thickening of the muscle walls of the lower left chamber of the heart (hypertrophic cardiomyopathy);
• valve leakage between the left upper (atrial) and lower (ventricular) chambers of the heart (mitral valve prolapse);
• and / or other heart defects.

Associated symptoms and signs may include:

• abnormal heart sounds (heart murmur) that can be detected by a doctor with a stethoscope;
• shortness of breath, especially with physical exertion;
• general ailments;
• chest pain;
• heart rhythm disturbances (arrhythmias);
• and / or other features that can lead to life-threatening complications without proper treatment.

Patients have an increased lifetime risk of developing malignant tumors such as muscle cancer (rhabdomyosarcoma), nerve cell cancer (neuroblastoma) and bladder cancer, and accounts for about 15% of all cases.

In some cases, the symptoms and signs of Costello syndrome overlap with two similar disorders known as Noonan syndrome and cardio-facio-cutaneous syndrome, which are caused by mutations in different genes.

Causes

Costello syndrome is inherited as an autosomal dominant genetic condition and is caused by mutations in the gene HRAS. Mutations in this gene result in the formation of an abnormal H-Ras protein, which leads to continuous cell growth and division.

Dominant genetic disorders occur when only one copy of an abnormal gene is needed to cause a specific disorder. An abnormal gene can be inherited from either parent or be the result of a new mutation (gene change) in a sick person. Most people with Costello syndrome have the disorder as a result of the new mutation. The risk of passing the abnormal gene from a sick parent to offspring is 50% with every pregnancy. The risk is the same for both men and women.

There have been several reports of several siblings with Costello syndrome in the family. This is most likely due to germ cell mosaicism, in which some of the parent's reproductive cells (germ cells) carry a gene mutation HRASwhile others contain the normal gene. As a result, one or more of the parent's children may inherit the gene mutation, resulting in an autosomal dominant disorder, but the parent may be asymptomatic.

Affected populations

Costello's syndrome is a very rare condition that affects men and women in relatively equal numbers. There are about 350 reported cases worldwide.

Diagnostics

Costello's syndrome is diagnosed based on the results of a clinical examination and specific diagnostic criteria have been developed for this. Molecular genetic testing for mutations in the gene is available to confirm the diagnosis. HRAS. Most clinically ill people have an identifiable mutation HRAS. Experts in the field have suggested that individuals without an identifiable mutation HRAS should not be diagnosed with Costello syndrome, as they are more likely to have an underlying medical condition, such as Noonan syndrome or cardio-facio-cutaneous syndrome.

A specific mutation in a gene is important for identification. HRASwhich is often referred to as a result of amino acid changes. Although most people with Costello syndrome have a common mutation that results in the replacement of the amino acid glycine at position 12 with serine, a number of changes are observed. The prognosis for a patient depends on the specific mutation, as some have more serious health problems than others.

Treatment of von Willebrand disease

Treatment for Costello syndrome targets specific symptoms that each person experiences. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, cardiologists, orthopedists, orthopedic surgeons, specialists diagnosing and treating skin abnormalities (dermatologists), speech therapists, nutritionists and other healthcare professionals require systematic and comprehensive treatment planning for the victim child.

Individuals with heart problems, such as hypertrophic cardiomyopathy, may be treated with certain drugs (for example, beta-blockers or calcium channel blockers, antiarrhythmic drugs), surgery and / or others measures. The specific surgical procedures will depend on the severity and location of the anatomical abnormalities, associated symptoms, and other factors.

Occupational therapy and physical therapy can be used to treat elbow wrist deviations. Surgery can be used to lengthen the Achilles tendon. Facial papillomas can be removed with dry ice.

Early intervention is essential for children with Costello syndrome to reach their potential. Services that may be helpful include special remedial education, speech therapy, special social support, and other medical, social and / or professional services.

Other treatments for the disorder are symptomatic and supportive.

Forecast

Costello's syndrome is a lifelong condition. Life expectancy often depends on the severity of the heart damage as well as other medical complications.