Costello syndrome - Symptoms, causes and treatment

Costello syndrome is a genetic disorder that can cause a range of symptoms, including developmental disorders, facial features, mental retardation, and heart problems. This condition occurs since the baby is still in the womb.

Costello syndrome is extremely rare and is estimated to occur in only 1 in 2.5 million people. This gene disorder can affect a number of systems in the body, including the brain, heart, muscles, skin, and spinal cord.

People with Costello syndrome are known to be at high risk for certain types of cancer, such as: rhabdomyosarcoma (cancer of the skeletal muscles) and neuroblastoma (cancer of the nervous system). Although there is no method to treat this condition, but proper treatment can help relieve the symptoms experienced.

Causes of Costello Syndrome

Costello syndrome is caused by mutations in the HRAS gene. Patients with Costello syndrome, both men and women, have a 50% risk of developing this condition with each pregnancy. However, Costello syndrome also often results from new mutations in the genes of the fetus from parents who do not have this condition.

The HRAS gene functions to produce H-Ras, a protein that helps control cell growth and division. HRAS mutations cause the H-Ras protein to be activated continuously so that cells continue to grow and divide. These conditions can trigger the growth of benign tumors or malignant tumors.

It is not known exactly how mutations in the HRAS gene cause Costello syndrome. However, experts suspect that this condition occurs due to uncontrolled cell growth and division.

Symptoms of Costello Syndrome

Costello syndrome can be detected before the baby is born through a pregnancy ultrasound. Symptoms that can be seen include:

Excess amniotic fluid in the uterus which can cause hydrops fetalis and polyhydramnios
Thickening in the fetal neck area
The size of the long bones, such as the thighbone which is shorter than normal
Abnormalities in the heart and kidneys
Fast fetal heart rate
Lymphatic dysplasia or abnormal cell growth around the spleen

Meanwhile, the symptoms of Costello syndrome that can be seen after birth include:

Head disorders, such as:

Large head size (macrocephaly)
Ear position lower than normal position
Big and thick ear lobes
Wide mouth
Thick lips
Big nostrils
Crossed eyes (strabismus)
Uncontrolled eye movement (nystagmus)
Hair loss and sagging facial skin that causes sufferers to look like old people

Developmental disorders, in the form of:

Difficult to increase weight and height
Difficulty eating
Mental retardation
Early puberty
Delays in walking or speaking

Musculoskeletal system disorders, including:

Osteoporosis to fractures
Tension of the Achilles tendon at the ankle
Spine curvature (kyphosis) or curvature (scoliosis)
Wrist bends towards the little finger
Weak muscle contractions
Joints are very flexible

Nervous system disorders, including:

Accumulation of cerebrospinal fluid (hydrocephalus)
Seizures
Imbalance in walking
Numbness or tingling in the hands and feet

Heart disorders, such as:

Heart rhythm disturbances
Chest pain
Congenital heart disease
Cardiomyopathy

Skin disorders, for example:

Warts that generally grow around the mouth and nostrils in children aged 2 years or older. In some cases, warts grow near the anus.
Thickened and blackened skin.
Cutis laxa or skin conditions that are overstretched and look saggy. This condition can occur in the neck area, fingers, palms, and soles of the feet.

When to go to the doctor

Symptoms of Costello syndrome can be seen from birth. Babies born in the hospital will usually immediately get the necessary examination and treatment.

If your baby shows any of the signs mentioned above and you don't give birth in a hospital, take the baby to a hospital immediately, especially one with a NICU facility.

If you or a member of your family has Costello syndrome, it is advisable to seek genetic counseling, especially if you are pregnant or planning a pregnancy. Consulting a doctor can help you determine the risk of this condition passing to your offspring.

Costello Syndrome Diagnosis

Just like in other genetic disorders, the diagnosis of Costello syndrome is quite difficult to make. During pregnancy, this condition can be suspected from the physical characteristics obtained on ultrasound examination of pregnancy and blood tests. However, DNA testing for HRAS gene mutations should be performed to confirm the diagnosis.

Meanwhile, in the case of Costello syndrome after birth, the examination will begin with questions and answers regarding the patient's symptoms and medical history. The diagnosis of Costello syndrome can generally be obtained by looking at the patient's physical signs.

To confirm the presence of HRAS gene mutations, doctors also need to do a DNA test. This is done to differentiate Costello syndrome from other conditions with similar symptoms, such as Noonan syndrome.

If necessary, the doctor will also carry out supporting examinations, such as:

MRI, to check the condition of the brain and spinal cord
Abdominal ultrasound and pelvic ultrasound
Electrocardiogram, to detect arrhythmias
Urine test, to check the presence of blood in the urine
Echocardiography, to detect abnormalities in the heart or heart valves

In pediatric patients, regular check-ups to the doctor are also necessary to detect abnormalities in the muscles and heart rhythm, as well as cancers in nerve cells, muscles, and bladder.

Costello Syndrome Treatment

Until now, there is no treatment method that can specifically treat Costello syndrome. Treatment is only limited to treating the symptoms experienced by the patient. Here are some of the treatment methods:

Feed replacement infusion with a nasogastric tube (a tube inserted through the nose into the esophagus until it reaches the stomach), or with a gastronomic tube (a tube inserted through the stomach wall into the stomach), to provide nutrition for the baby
Medicines and surgical procedures to treat heart problems
Physiotherapy, occupational therapy, and physical therapy to treat developmental disorders
Surgical procedure to lengthen the short Achilles tendon so the child can walk, run and play better
Treatment to a dermatologist to remove warts and improve skin thickening
Growth hormone therapy to treat growth disorders and control metabolism

Costello Syndrome Complications

Complications that need to be watched out for in Costello syndrome are complications from heart problems. If not treated properly, the heart problems in Costello syndrome can lead to heart failure or sudden cardiac arrest.

In addition, genetic disorders that are owned by people with Costello syndrome make them more at risk of developing malignant cancers, such as muscle tissue cancer (such as rhabdomyosarcoma), nerve cancer (neuroblastoma), and bladder cancer.