SNP Shot: Genomic Insights

Noonan syndrome is a multi-system disorder characterized by a range of features, including subtle differences in facial appearance, short stature, heart problems, bleeding tendencies, skeletal issues, and other varying signs and symptoms.

Individuals with Noonan syndrome often share distinct facial characteristics. These can include a prominent groove between the nose and upper lip (philtrum), wide-set eyes typically light blue or blue-green, and ears that sit low and are rotated backward. Other possible facial features include a high-arched palate, misaligned teeth, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck, and individuals of all ages may have excess skin folds on the neck (webbing) and a low hairline at the nape of the neck.

Short stature is observed in 50% to 70% of individuals with Noonan syndrome. While birth length and weight are generally normal, growth rate typically slows down over time. This slow growth can be attributed to abnormal levels of growth hormone, a vital protein for bone and tissue development.

Individuals affected by Noonan syndrome frequently exhibit chest deformities, either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Spinal curvature (scoliosis) may also be present in some individuals.

A significant portion of individuals with Noonan syndrome have some form of congenital heart defect. The most common is pulmonary valve stenosis, a narrowing of the valve controlling blood flow from the heart to the lungs. Hypertrophic cardiomyopathy, a condition that causes thickening and weakening of the heart muscle, can also occur.

Bleeding disorders are frequently associated with Noonan syndrome. This may present as easy bruising, nosebleeds, or prolonged bleeding after injuries or surgical procedures. In rare cases, women with Noonan syndrome who also have a bleeding disorder may experience heavy menstrual bleeding (menorrhagia) or excessive bleeding after childbirth.

Adolescent males with Noonan syndrome often experience a delay in puberty, starting around age 13 or 14. Their pubertal growth spurt is typically reduced, contributing to shorter adult height. Undescended testes (cryptorchidism) is also common in males with Noonan syndrome and can lead to infertility later in life. Puberty and fertility are usually normal in females with Noonan syndrome, although a delay in puberty is possible.

Noonan syndrome can manifest in diverse ways. While most children with the condition have normal intelligence, some may require special education support, and a few may have intellectual disabilities. Vision and hearing problems are also possible. Feeding difficulties may be present in infants but usually resolve by ages 1 or 2. Swelling due to fluid buildup (lymphedema) may be present at birth in the hands and feet and tends to resolve. Lymphedema can also develop later in life, especially in the ankles and lower legs.

Individuals with Noonan syndrome have an increased risk of developing certain cancers, particularly leukemia. Children with Noonan syndrome are estimated to have an eight times higher risk of developing leukemia or other cancers compared to their peers.

Noonan syndrome belongs to a group of related conditions known as RASopathies. These conditions share similar features and result from alterations in the same cell signaling pathway. Besides Noonan syndrome, RASopathies include cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, Legius syndrome, and Noonan syndrome with multiple lentigines.

Inheritance:

Noonan syndrome follows an autosomal dominant inheritance pattern. This means that only one copy of the affected gene in each cell is enough to cause the condition.