Signs and Symptoms of Costello Syndrome | Cardiology

Costello syndrome

What is Costello syndrome?

Costello syndrome is a very rare genetic condition. It occurs when there is a change (mutation) in a gene called the HRAS gene. This happens in a child’s DNA before birth.

Costello syndrome causes glitches that affect the heart, muscles, bones, skin, brain, and spinal cord. There is no cure for the condition, but doctors can help children control most symptoms.

Alternate name

  • Faciocutaneoskeletal syndrome

Causes of Costello syndrome

Mutations in the HRAS gene cause Costello syndrome. This gene provides orders for making a protein called H-Ras, which is part of a pathway that helps control cell growth and division. The mutations that cause Costello syndrome to lead to the production of an H-Ras protein that is turned on (activated) in an abnormal way. The overactive protein causes cells to constantly grow and divide, which can lead to the development of cancerous and non-cancerous tumors. It is not clear how mutations in the HRAS gene cause the other features of Costello syndrome, but many of the signs and symptoms are likely the result of excessive cell growth and abnormal cell division.

Some people with signs and symptoms such as Costello syndrome do not have an identified mutation in the HRAS gene. These individuals may have CFC syndrome or Noonan syndrome, which are caused by mutations in related genes. The proteins produced from these genes interact with each other and with the H-Ras protein as part of the same cell growth and division pathway. These interactions help explain why mutations in different genes can cause conditions with overlapping signs and symptoms.

Signs and symptoms of Costello syndrome

Babies with Costello syndrome are usually of normal or high birth weight, but show poor sucking ability, have difficulty swallowing, and do not grow or gain weight at the expected rate (growth retardation). Growth delay after birth generally results in short stature during childhood and adulthood. Affected children may have a developmental delay or mild to moderate intellectual disability. In some people, the development of speech and/or the ability to walk is significantly delayed. Children with Costello syndrome generally have warm and sociable personalities.

People with Costello syndrome often have loose skin (cutis laxa) on the neck, palms, fingers, and soles of the feet. The skin in these areas may lack elasticity and become loose; Furthermore, the skin may appear wrinkled and thickened. In some cases, certain areas of the skin may turn unusually dark (hyperpigmentation). Also, most patients with this disorder develop dry, hardened patches of skin (hyperkeratosis) with unusually deep folds on the palms and soles of the feet. Some affected individuals may also have skeletal abnormalities such as disrupted hips, abnormally flexible (hyperextensible) finger joints, wrists bent toward the little finger (ulnar deviation), and/or unusual tension of the fibrous cords at the back of the heels (Achilles tendon). Other skeletal abnormalities include side-to-side curvature of the spine (scoliosis), front-to-back curvature of the spine (kyphosis), and reduced range of motion in the shoulders and elbows.

Children with Costello syndrome often develop papillomas around the mouth and nasal passages. Papillomas can develop as young as two years of age or older. In some cases, these wart-like lesions (warts) can be found near the anus. Papillomas generally become more apparent with age. Other benign tumors have also been reported.

Children with Costello syndrome have a characteristic facial appearance. Characteristic facial features may include an abnormally large head (macrocephaly); low-set ears with large, thick lobes; unusually thick lips; a large, depressed bridge of the nose; abnormally wide nostrils (nostrils); and a rough facial appearance. Also, affected children may have unusually curly hair and/or sparse, thin hair on the front (anterior) part of the head. Some children have folds of skin over the inner corners of the eyes (epicanthus folds).

In early childhood, the relative overgrowth of the rhombencephalon compared to the available space in the posterior fossa of the skull cavity can lead to thronging and neurological problems. Because severe crowding requires surgical intervention, magnetic resonance imaging of the brain and cervical spine has been suggested.

Changes in the eyes and vision are shared and include nystagmus (rapid eye movements) in younger individuals, strabismus, and rarely keratoconus (abnormal thickening of the cornea) in older individuals.

Children with Costello syndrome often have sure heart abnormalities. These may include structural malformations of the heart that are present at birth (congenital heart defects); abnormal thickening of the muscular 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. Symptoms and associated findings may include abnormal heart sounds (heart murmurs) that can be detected by a physician using a stethoscope; shortness of breath, particularly when exercising; weakness; chest pain; abnormal heart rhythms (arrhythmias); and/or other findings that can potentially lead to life-threatening complications without proper treatment.

Affected people have an approximately 15% lifetime risk of developing malignant tumors, such as cancer of the muscle tissue (rhabdomyosarcoma), cancer of the nerve cells (neuroblastoma), and transitional cell carcinoma of the bladder.

In some cases, the symptoms and answers of Costello syndrome overlap with two similar disorders recognized as Noonan syndrome and cardiofaciocutaneous syndrome that are caused by mutations in different genes.

Diagnosis of Costello syndrome

Costello syndrome is very rare, so a doctor is unlikely to immediately suspect it.

A doctor will begin by assessing the child’s height, head size, and birth weight.

The next stage includes molecular genetic testing. Sequence analysis is approved out on the HRAS gene to see if there is an alteration related to Costello syndrome.

Treatment for Costello syndrome

There is no cure for Costello syndrome, nor is there any specific treatment, but aspects of the syndrome, for example, heart conditions, hypertrophic cardiomyopathy, can be specifically treated.

Ways to help the individual manage the condition include:

  • Help a child overcome feeding difficulties during infancy
  • Treatment for heart problems
  • Providing special education
  • Researchers are looking for an effective way to treat the condition at the genetic level.

Other interventions include:

  • Physical therapy and occupational therapy
  • Surgery to lengthen the Achilles tendon
  • Removal of papillomas with cryotherapy


Costello syndrome is a complex, multi-system condition that can lead to a variety of complications.

Babies may not be able to feed by mouth until they are 2 to 4 years old, or around the same time, they begin to speak.

Cardiovascular problems usually appear from early childhood, although symptoms may not appear until later. These include congenital heart defects and cardiac hypertrophy. The person may experience tachycardia or rapid heartbeat and arrhythmias or irregular heart rhythms.

Macrocephaly, or overgrowth of the brain, has been observed in 50 percent of patients. This can lead to a Chiari malformation, a structural defect in the brain found in 32 percent of people, according to one study. Seizures appear to affect between 20 and 50 percent of people with the condition.

There may be delays in bone growth, low bone density, and an increased risk of bone fractures and osteoporosis. Vitamin D and calcium supplements can help.

Tumors, most commonly papillomas, small growths that resemble warts, can develop, especially around the nose, mouth, and anus.

People with Costello syndrome are prone to developing cancerous and non-cancerous tumors. Cancerous tumors include rhabdomyosarcoma, neuroblastoma, and transitional cell carcinoma.

Two other genetic conditions with similar symptoms are Noonan syndrome and cardiofaciocutaneous syndrome (CFC). Overlapping symptoms make it difficult to diagnose Costello syndrome during childhood.

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