Noonan syndrome is a genetic disorder caused by mutations in genes involved in a key cell signaling pathway known as the RAS/MAPK pathway. This condition is present from birth and is characterized by a wide and varied range of physical features and health issues that can change significantly as a person ages5. Because its presentation can range from very mild to severe, a diagnosis is often made based on a clinical evaluation of these characteristic symptoms, which can affect many different parts of the body, from facial appearance to heart function410. The signs may be subtle, especially in infancy, but often become more apparent during early childhood20.
The most recognizable signs of Noonan syndrome involve distinctive physical features, though these can become less obvious in adulthood11. Many individuals have widely spaced eyes (hypertelorism) with down-slanting eyelid folds, drooping eyelids (ptosis), and low-set ears that may be rotated backward10. Other common facial traits include a short neck with excess skin (webbed neck), a high forehead, and a small lower jaw10. In early childhood, the face may appear broad, but it often lengthens into a more triangular shape with age, sometimes with signs of premature aging4. Beyond facial features, short stature is a very common characteristic, and growth may slow over time10. Skeletal differences are also frequently observed, including an unusually shaped chest, such as a breastbone that protrudes outward (pectus carinatum) or sinks inward (pectus excavatum)10.
Beyond the visible physical traits, Noonan syndrome is associated with several significant health conditions affecting various organ systems10. Congenital heart defects are present in a majority of individuals, with the most common being pulmonic stenosis (a narrowing of the valve that controls blood flow from the heart to the lungs) and hypertrophic cardiomyopathy (a thickening of the heart muscle)10. Many individuals also experience developmental delays, which can range from mild learning disabilities to more significant intellectual challenges, and may include delayed speech or motor milestones10. Other potential issues include:
- Bleeding problems, such as easy bruising or prolonged bleeding after injury or surgery, often due to a deficiency in clotting factors like factor XI10.
- Lymphatic system abnormalities, which can cause fluid buildup (lymphedema), particularly in the extremities, or fluid-filled sacs (cystic hygromas) detected before birth10.
- In males, undescended testicles (cryptorchidism) are common and can affect fertility later in life, even if surgically corrected.
- Eye and ear problems, including crossed eyes (strabismus) and hearing loss15.
- Feeding difficulties in infancy, which may contribute to a failure to thrive in the first few months of life20.
What does a child with Noonan syndrome look like?
A child with Noonan syndrome often has distinct facial features that can be subtle and may become less noticeable as they get older11. These characteristics typically include wide-set, downward-slanting eyes, often with droopy eyelids (ptosis)10. Their ears are usually low-set and rotated toward the back of the head15. Other common physical traits are a short neck, which may have extra folds of skin, a tall forehead, and a nose with a wide base10. In addition to facial features, many children with the condition have short stature and a chest that appears either sunken in (pectus excavatum) or pushed out (pectus carinatum)10.
What is the daddy long legs syndrome?
"Daddy long legs syndrome" is an informal name for Marfan syndrome, a genetic disorder that affects the body's connective tissue19. The nickname stems from the condition's most prominent physical features: a tall, slender build with disproportionately long arms, legs, fingers, and toes183. Caused by a mutation in the gene that produces fibrillin-1, a protein essential for tissue elasticity and strength, Marfan syndrome impacts multiple body systems193. While the skeletal signs are the most visible, the most dangerous complications involve the heart and aorta, which can weaken and stretch, leading to life-threatening conditions like an aortic aneurysm194. The disorder can also cause significant issues with the eyes, spine, and lungs19.
At what age is Noonan syndrome diagnosed?
Noonan syndrome can be diagnosed at various stages of life, from before birth to adulthood115. In some cases, prenatal genetic testing can identify the condition, particularly if there is a family history or if ultrasounds show potential signs like excess amniotic fluid155. More frequently, diagnosis occurs in infancy or early childhood when key characteristics, such as specific facial features or congenital heart defects, are recognized by doctors20. Because the symptoms can be very mild and subtle, some individuals may not be diagnosed until later in childhood or even as adults, sometimes only after their own child is diagnosed with the condition204.
What is Noonan syndrome like?
Living with Noonan syndrome varies greatly from person to person, as symptoms can range from mild to more significant and may change with age16. Individuals often have distinct facial features, such as wide-set and downward-slanting eyes, a short or webbed neck, and a shorter stature compared to their peers103. Daily life may involve managing various health conditions, most commonly congenital heart defects, as well as potential bleeding disorders, feeding difficulties in infancy, or vision and hearing problems5. While most people with the condition have normal intelligence, some experience developmental delays, learning disabilities, or speech difficulties that require therapeutic and educational support10. With ongoing care to manage symptoms and complications, individuals can lead full and active lives113.
Is Noonan syndrome a form of dwarfism?
Noonan syndrome is a genetic condition in which short stature is a very common clinical feature14. Medically, dwarfism is defined as having a height below the third percentile or two standard deviations below the mean for a person's age and sex21. Because a significant percentage of individuals with Noonan syndrome meet this criterion, it is recognized as a syndromic cause of dwarfism, alongside other genetic conditions like Turner syndrome and achondroplasia10. As one of the more common RASopathy conditions, Noonan syndrome is frequently included in the differential diagnosis for children being evaluated for pathologic short stature and is sometimes classified as a genetic short stature disorder274.
What are the neurological effects of Noonan syndrome?
Noonan syndrome (NS) impacts neurological development due to mutations in the RAS/MAPK pathway, which is essential for processes like neural activity and plasticity24. This can lead to a variety of cognitive difficulties, most notably affecting memory, attention, visual processing, and executive functions24. A characteristic finding in individuals with NS is that recall memory is more impaired than recognition memory, a pattern linked to dysfunction in the hippocampus and prefrontal networks24. Furthermore, attention deficits are common, with approximately 30% of individuals receiving an ADHD diagnosis, and many children experience delays in communication skills24. Despite these specific challenges, the majority of people with NS (50-66%) have average or above-average intellectual abilities, and studies show that IQ scores often improve throughout their lifespan243.
What is the difference between Noonan syndrome and Williams syndrome?
Noonan syndrome and Williams syndrome are distinct genetic disorders with different underlying causes and clinical presentations16. Williams syndrome results from a microdeletion on chromosome 7q11.23, which includes the elastin ( ELN ) gene, leading to characteristic "elfin-like" facial features, supravalvular aortic stenosis, hypercalcemia, and a uniquely sociable personality with strong verbal skills28. In contrast, Noonan syndrome is a RASopathy caused by mutations in genes of the RAS-MAPK signaling pathway, such as PTPN11 or SOS1 . It is typically characterized by different facial features like wide-set eyes and low-set ears, a high incidence of pulmonary valve stenosis or hypertrophic cardiomyopathy, short stature, and potential bleeding disorders273. While both syndromes can involve heart defects and developmental delays, the specific genetic pathways and hallmark features clearly differentiate them273.
