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Costello syndrome

Costello syndrome is a genetic disorder that affects many parts of the body. This condition is characterized by delayed development and mental retardation, distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints. Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but have difficulty feeding and grow more slowly than other children. Later in life, people with this condition have relatively short stature and many lack growth hormone. more...

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Beginning in early childhood, people with Costello syndrome have an increased risk of developing certain cancerous and noncancerous tumors. Small growths called papillomas are the most common noncancerous tumors seen with this condition. They usually develop around the nose and mouth or near the anus. The most frequent cancerous tumor associated with Costello syndrome is a soft tissue tumor called a rhabdomyosarcoma. Other cancers also have been reported in children and adolescents with this disorder, including a tumor that arises in developing nerve cells (neuroblastoma) and a form of bladder cancer (transitional cell carcinoma).

Genetics

Mutations in the HRAS gene cause Costello syndrome. The HRAS gene provides instructions for making a protein that helps control cell growth and division. Mutations that cause Costello syndrome lead to the production of an HRAS protein that is permanently active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. This unchecked cell division can cause cancerous and noncancerous tumors to develop. It remains unclear how mutations in the HRAS gene cause the other features of Costello syndrome, but many of the signs and symptoms probably result from cell overgrowth and abnormal cell division.

This condition is considered to have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Almost all cases have resulted from new mutations in the gene, and occur in people with no history of the disorder in their family. This condition is rare; 150 to 200 cases have been reported worldwide.

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