Rasopathy disorders

The RAS pathway is a part of the body that regulates each person's growth and function. It is critical to each person's normal, early development. If this pathway is disrupted by a genetic change in a child's development, there can be a variety of symptoms, including skin changes, heart defects, problems with muscles, bones, eyesight and learning abilities. In some cases, there is an increased risk of developing tumors or cancer.

RASopathies are a group of genetic conditions caused by changes in genes that are part of the RAS pathway. These gene changes can occur on their own or be inherited from a parent.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a condition that has many small blood vessel differences, known as capillary malformations, mostly on the face, arms and legs. In addition, some individuals also have an abnormal connection between an artery and a vein in the skin, muscle, bone, spine or brain, known as arteriovenous malformations or fistulas. These can have significant effects, sometimes causing life-threatening complications including bleeding, heart failure or brain problems. CM-AVM most often is inherited from a parent, but sometimes results from a new change in an individual's gene, so the individual may be the first person in the family to have the condition.

Cardio-facial-cutaneous (CFC) syndrome is a condition characterized by:

  • Heart problems such as heart defects or problems with heart function.
  • Facial features that are very specific.

Skin, hair and nail problems such as different types of birthmarks or skin that is rough looking or thickened in some areas. Hair may be thin, curly or brittle. Occasionally there will be very few eyelashes or the eyelashes and eyebrows will be missing. Fingernails or toenails may be flat and broad.

Other findings of CFC syndrome include feeding problems and growth delays. In addition, individuals with CFC often have low muscle tone and developmental delays. There may be an increased risk for certain types of cancer in some individuals with CFC. CFC typically is due to a new change in an individual's gene and usually is not inherited from a parent.

Costello syndrome is a condition that includes feeding and growth difficulties, heart defects and problems with heart function and the skin, and specific facial features. Skin problems include growths on the face and anus called papillomata, and loose, soft skin with deep creases in the hands and feet. Individuals with Costello syndrome also may have curly or thin, fine hair.

Other features of Costello syndrome include developmental delays, shorter height and a sociable, outgoing personality. The wrists and fingers may develop in a very specific way. Individuals with Costello syndrome have approximately a 15 percent lifetime risk for cancerous tumors. Costello syndrome is typically due to a new change in an individual's gene and usually is not inherited from a parent.

Multiple lentigines syndrome (formerly known as LEOPARD (LS) syndrome)
The features of this condition include:

  • Lentigines, which are flat, black-brown spots, mostly on the face, neck and chest that generally appear around age 4 or 5 and increase in number over time. Some individuals with LS do not have lentigines. Some individuals with LS also have brown birthmarks called cafe-au-lait spots.
  • ECG, which include problems with how the heart works.
  • Ocular hypertelorism, described as wide-spaced eyes.
  • Pulmonic stenosis, described as narrowing of the heart's pulmonary valve.
  • Abnormal genitalia, which most often involves undescended testes in males.
  • Retardation of growth, which means that some individuals with LS have a delay in growth that leads to shorter height. However, birth size may be normal or even large.
  • Deafness or hearing loss.

Some individuals with multiple lentigines syndrome have mild developmental delays. Symptoms of LS vary, so a diagnosis is made based on a number of medical factors. LS can be inherited from a parent or result from a new change in an individual's gene, so the individual may be the first person in the family to have the condition.

Noonan syndrome (NS) is a condition that has specific physical signs, including a broad, webbed neck, a chest bone that sticks out and wide-spaced eyes with droopy eyelids. Many individuals with NS also have heart problems. They may be born with a heart defect such as pulmonic stenosis, which is a narrowing of the pulmonary valve of the heart, or have hypertrophic cardiomyopathy, a problem with the function of the heart, which makes it larger than normal. Males with NS can have undescended testes. Learning problems sometimes are associated with NS. People with NS often are shorter than other people in their family. NS can be inherited from a parent or result from a new genetic change, so the individual may be the first person in the family to have the condition. If a parent has NS, there is a 50 percent chance his or her child also will have NS. This is called autosomal dominant inheritance.