p.1
Definition
Noonan syndrome is a condition usually involving a heart problem found at birth, short stature, a broad or webbed neck, pectus excavatum and pectus carinatum (chest deformities), as well as a range of developmental delays. Occasionally, café-au-lait spots (a skin finding) and other features of neurofibromatosis may be present.
Description
First described by the pediatrician and heart specialist Jacqueline Noonan in 1963, Noonan syndrome includes numerous specific features. However, no two affected individuals typically have the exact same combination of these characteristics. There still is no defined list of criteria to diagnose the condition, and no molecular genetic testing exists to confirm a diagnosis. Therefore, attributing an individual's features to Noonan syndrome is based upon a careful review of medical and family history, a detailed physical examination, and study of other possible diagnoses.
There are three major groups of Noonan syndrome. The classical type is Noonan syndrome, Type 1 (NS1). This is also known as Noonan syndrome, Male Turner syndrome, Female pseudo-Turner syndrome, Turner phenotype with normal karyotype, and Pterygium colli syndrome. NS1 has been called Male Turner syndrome because so many features overlap between NS1 and Turner syndrome. The striking difference between the two conditions is that Turner syndrome is caused by a chromosome abnormality, and affects females only. In contrast, men and women are affected with Noonan syndrome equally.
Individuals with NS1 may often have a heart defect, pulmonic stenosis, found at birth. A chest wall abnormality is common, typically with pectus carinatum at the upper portion (near the neck) and pectus excavatum below it, creating a "shield-like" appearance. Developmental delays are sometimes a part of the condition.
Facial features such as a tall forehead, wide-set eyes, low-set ears, and a short neck are common. Young children with NS1 often have very obvious facial features, and may have a "dull" facial expression, similar to conditions caused by muscle weakness. However, facial features may change over time, and adults with Noonan syndrome often have more subtle facial characteristics. This makes the face a less obvious clue of the condition in older individuals. Other associated features in NS1 are smaller genitalia in males, as well as cryptorchidism. Some individuals with the condition develop thrombocytopenia, or a low number of blood platelets, as well as other problems with normal blood coagulation (clotting).
Another type of the condition is Noonan syndrome, Type 2 (NS2). This involves the same characteristic features as Type 1, but the inheritance pattern is proposed as recessive, rather than the more commonly seen dominant pattern.
The final type of the syndrome is neurofibromatosis-Noonan syndrome, also known as Noonan-neurofibromatosis syndrome, and neurofibromatosis with Noonan Phenotype. In this, individuals often have some features of both neurofibromatosis and NS1. It has been proposed that this may simply be a chance occurrence of two conditions. This is because these conditions have two distinct gene locations, with no apparent overlap.
Genetic profile
In 1994, Ineke van der Burgt and others discovered the gene for Noonan syndrome is located on chromosome 12, on the q (large) arm. They found this through careful studies of a large Dutch family, as well as 20 other smaller families, all with people affected by Noonan syndrome. Research studies are taking place to further narrow down the gene location. It is proposed to be at 12q24 (band 24 on the q arm of chromosome 12).
Historically, NS1 has been inherited in an autosomal dominant manner, and this is still the most common inheritance pattern for the condition. This means that an affected individual has one copy of the mutated gene, and has a 50% chance to pass it on to each of his or her children, regardless of that child's gender. About half of people with Noonan syndrome have a family history of it. For the other half, the mutated gene presumably occurred as a new event in their conception, so they would likely be the first person in their family to be diagnosed with the condition.
New studies have identified evidence for other inheritance patterns. van der Burgt and Brunner studied four Dutch individuals with Noonan syndrome and their families and proposed an autosomal recessive form of the condition, NS2. In autosomal recessive conditions individuals may be carriers, meaning that they carry a copy of a mutated gene. However, carriers often do not have symptoms of the condition. Someone affected with an autosomal recessive condition has two copies of a mutated gene, having inherited one copy from their mother, and the other from their father. Thus, only two carrier parents can have an affected child. For each pregnancy that two carriers have together, there is a 25% chance for them to have an affected child, regardless of the child's gender. Consanguineous parents (those that are blood-related to each other) are more likely (when compared to unrelated parents) to have similar genes. Therefore, two consanguineous parents may have the same abnormal genes, which together may result in a child with a recessive condition. The hallmark feature of the families in the Dutch study is that the parents of the affected children were consanguineous, making an autosomal recessive form of Noonan syndrome a possibility
p.2
Demographics
Noonan syndrome is thought to occur between one in 1,000 to one in 2,500 live births. There appears to be no ethnic bias in Noonan syndrome, though many studies have arisen from Holland, Canada, and the United States.
Signs and symptoms
Occasionally, feeding problems may occur in infants with Noonan syndrome, because of a poor sucking reflex. Short stature by adulthood is common, though birth length is typically normal. Developmental delays may become apparent because individuals are slower to attain milestones, such as sitting and walking. Behavioral problems may be more common, but often are not significant enough for medical attention. Heart defects are common, with pulmonary stenosis being the most common defect. Muscle weakness is sometimes present, as is increased flexibility of the joints. Less common neurologic complications may include schwannomas, or growths (common in neurofibromatosis) of the spinal cord and brain. These schwannomas may also occur in the muscle.
Many facial features are found in Noonan syndrome, often involving the eyes. Eyes may be wide-set, may appear half-closed because of droopy eyelids, and the corners may turn downward. Some other findings, such as nystagmus and strabismus may occur. Interestingly, most people with Noonan syndrome have beautiful pale blue- or green-colored eyes. Often, the ears are low-set (lower than eye-level), and the top portion of cartilage on the ear is folded down more than usual. Hearing loss may occur, most often due to frequent ear infections. A very high and broad forehead is very common. An individual's face may take on an inverted triangular shape. As mentioned earlier, facial features may change over time. An infant may appear more striking than an adult does, as the features may gradually become less obvious. Sometimes, studying childhood photographs of an individual's presumably "unaffected" parents may reveal clues. Parents may have more obvious features of the condition in their childhood photographs.
Chest wall abnormalities such as a shield chest, pectus carinatum, and pectus excavatum occur in 90-95% of people with NS1. These are thought to occur because of early closure of the sutures underneath these areas. Additionally, widely-spaced nipples are not uncommon. Scoliosis (curving of the spine) may occur, along with other spine abnormalities.
Lymphatic abnormalities may be common, often due to abnormal drainage or blockage in the lymph glands. This may cause lymphedema, or swelling, in the limbs. Lymphedema may occur behind the neck (often prenatally) and this is thought to be the cause of the broad/webbed neck in the condition. Prenatal lymphedema is thought to obstruct the proper formation of the ears, eyes, and nipples as well, causing the mentioned abnormalities in all three.
Individuals with Noonan syndrome may have problems with coagulation, shown by abnormal bleeding or mild to severe bruising. von Willebrand disease and abnormalities in levels of factors V, VIII, XI, XII, and protein C (all proteins involved in clotting of blood) are common, alone or in combination. These problems may lessen as the person ages, even though the mentioned coagulation proteins may still be present in abnormal amounts. Rarely, some forms of leukemia and other cancers occur.
Kidney problems are often mild, but can occur. The most common finding is a widening of the pelvic (cupshaped) cavity of the kidney. In males, smaller penis size and cryptorchidism are sometimes seen. Cryptorchidism may lead to improper sperm formation in these men, although sexual function is typically normal. It is not as common to see an affected man have a child with Noonan syndrome, and this is probably due to cryptorchidism. Puberty may be delayed in some women with NS1, but fertility is not usually compromised.
Lastly, follicular keratosis is common on the face and joints. It is a set of dark birthmarks that often show up during the first few months of life, typically along the eyebrows, eyes, cheeks, and scalp. Generally, it progresses until puberty, then stops. Sometimes it may leave scars, which may prevent hair growth in those areas. café-au-lait spots can occur, not unlike those seen in neurofibromatosis
p.3
Diagnosis
There are no molecular or biochemical tests for Noonan syndrome, which would aid in confirming a diagnosis. Therefore, it is a clinical diagnosis, based on findings and symptoms. The challenge is that there are several conditions that mimic Noonan syndrome. If a female has symptoms, a chromosomal study is crucial to determine whether she has Turner syndrome, as she would have a missing X chromosome. Other chromosomal conditions that are similar include trisomy 8p (three copies of the small arm of chromosome 8) and trisomy 22 mosaicism (mixed cell lines with some having three copies of chromosome 22). A karyotype would help to rule these out.
An extremely similar condition is Cardio-facio-cutaneous syndrome (CFC), which has similar facial features, short stature, lymphedema, developmental delays, as well as similar heart defects and skin findings. It has been debated as to whether CFC and NS1 are the same condition. The most compelling argument that they are two, distinct condition lies with the fact that all cases of CFC are sporadic (meaning there is no family history), whereas NS1 may often be seen with a family history.
Other similar conditions include Watson and multiple lentigines/LEOPARD syndrome, as they are associated with pulmonary stenosis, wide-set eyes, chest deformities and mental delays. Careful study would identify Noonan syndrome from these.
Most individuals are diagnosed with NS1 in childhood, however some signs may present in late stages of a pregnancy. Lymphedema, cystic hygroma, and heart defects can sometimes be seen on a prenatal ultrasound. With high-resolution technology, occasionally some facial features may be seen as well. After such findings, an amniocentesis would typically be offered (as Turner syndrome would also be suspected) and a normal karyotype would further suspicion of NS1.
Treatment and management
Treatment is very symptom-specific, as not everyone will have the same needs. For short stature, some individuals have responded to growth hormone therapy. The exact cause of the short stature is not well defined, and therapies are currently being studied. Muscle weakness and early delays often necessitate an early intervention program, which combines physical, speech, and occupational therapies. Heart defects need to be closely followed, and treatment can sometimes include beta-blockers or surgeries, such as opening of the pulmonary valve. For individuals with clotting problems, aspirin and medications containing it should be avoided, as they prevent clotting. Treatments using various blood factors may be necessary to help with proper clotting. Drainage may be necessary for problematic lymphedema, but it is rare. Cryptorchidism may be surgically corrected, and testosterone replacement should be considered in males with abnormal sexual development. Back braces may be needed for scoliosis and other skeletal problems. Unfortunately, medications such as creams for the follicular keratosis are usually not helpful. Developmental delays should be assessed early, and special education classes may help with these. In summary, these various treatment modalities require careful coordination, and many issues are lifelong. A team approach may be beneficial.
Prognosis
Prognosis for Noonan syndrome is largely dependent on the extent of the various medical problems, particularly the heart defects. Individuals with a severe form of the condition may have a shorter life span than those with a milder presentation. In addition, presence of mental deficiency in 25% of individuals affects the long term prognosis.
.................................................
if you wanna make a lil extra money click on the banner^^^^ talk to THEONE she'll help ya out on wut ya can do chat is free by the way so feel free to drop by and say hi make sure u tell her how you found the site and guys can sign up as a high roller to get private shows from some of the girls on there.
