Noonan syndrome Guide, Meaning , Facts, Information and Description
Noonan Syndrome (NS) is a relatively common congenital genetic condition which affects both males and females. The principal features include congenital heart malformation, short stature, learning problems, indentation of the chest, impaired blood cloting, and a characteristic configuration of facial features. NS is one of the most common conditions associated with congenital heart anomalies, especially those of the right heart. The syndrome is named after Dr Jacqueline Noonan, a paediatric cardiologist based in Kentucky.It is believed that 1 in 1,000 to 1 in 2,500 children worldwide are born with Noonan syndrome. It is one of the most common genetic syndromes associated with congenital heart malformations, similar in frequency to Down syndrome. However, the body features are much less obviously abnormal, and many if not most affected persons go undiagnosed.
| Table of contents |
|
2 Manifestations by organ system 3 Diagnosis 4 Treatment 5 History 6 See also 7 External links |
Cause
Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with autosomal dominant inheritance and variable expression. A clearly affected person had up to a 50% chance of transmitting it to a child. The fact that affected parents cannot be identified for many children with Noonan syndrome suggests that (1) a parent could carry the gene without being affected, (2) that manifestations were variably expressed and could be so subtle as to go unrecognized, (3) that a high proportion of cases represented new, sporadic mutations, or 4) that Noonan syndrome is heterogeneous, comprised of more than one similar condition of differing cause, some not inherited.
In most of the families with multiple affected members, Noonan syndrome mapped to chromosome 12q24.1 In 2001, it was reported that approximately half of a group of patients with Noonan syndrome carried a mutation of the PTPN11 gene at that location, which encodes protein tyrosine phosphatase SHP-2 (Tartaglia M, et al. Nature Genetics 2001;29:465-468). The protein SHP-2 is a component of several intracellular signal transduction systems involved in embryonic development that modulate cell division,differentiation, and migration, including that mediated by the epidermal growth factor receptor. The latter pathway is important in the formation of the cardiac semilunar valvess.
Noonan syndrome has been assigned OMIM number 163950 [1].
HEART —(2/3 of pts have a heart defect)
Jacqueline Noonan is a pediatric cardiologist and pediatrician, now based in Kentucky, who qualified in Boston in 1956. When she subsequently began work at the University of Iowa as their first pediatric cardiologist, she noticed that children with a rare type of heart defect, valvular pulmonary stenosis, often had a characteristic physical appearance with short stature, webbed neck, wide spaced eyes, and low-set ears. Both boys and girls were affected. Even though these characteristics were sometimes seen running in families, chromosomes appeared grossly normal. She studied 833 patients at the congenital heart disease clinic, looking for other congenital abnormalities, and in 1962 presented a paper: "Associated non-cardiac malformations in children with congenital heart disease". This described 9 children who in addition to congenital heart disease had characteristic faces, chest deformities and short stature. Both males and females were found to be similarly affected, and the chromosomes were apparently normal.
Dr John Opitz, a former student of Dr Noonan, first began to call the condition "Noonan Syndrome" when he saw children who looked like those whom Dr Noonan had described. Dr Noonan later produced a paper entitled "Hypertelorism with Turner Phenotype", and in 1971 at the Symposium of Cardiovascular defects, the name 'Noonan Syndrome' became officially recognized.
This is an Article on Noonan syndrome. Page Contains Information, Facts Details or Explanation Guide About Noonan syndrome Manifestations by organ system
The most prevalent (common) signs are highlighted in bold with frequency listed in parentheses.
GASTROINTESTINAL SYSTEM
GENITO-URINARY SYSTEM
LYMPHATIC SYSTEM
DEVELOPMENTAL
MUSCULOSKELETAL
HEMATOLOGIC —(1 in 5 pts have a bleeding disorder)
By physical appearance
STATURE/POSTURE
HEAD
EYES
NOSE
EARS/HEARING
MOUTH/SPEECH
LIMBS/EXTREMITIES
SKIN
Diagnosis
Despite identification of a candidate gene, the diagnosis of Noonan syndrome is still based on clinical features. In other words, it is made when a physician feels that a patient has enough of the features to warrant the label indicating association. It is likely that a specific gene test will become available soon, but absence of the specific mutation will not exclude the diagnosis. The principal values of making such a diagnosis are that it suggests other problems to check for, it excludes other possible explanations for the features, and it suggests the possibility of recurrence risk in siblings or offspring of the patient. Treatment
Each specifc abnormality can be treated as if it occurred in isolation. A congenital heart malformation can be corrected surgically. Undescended testes can be brought into the scrotum surgically. Growth hormone is sometimes given to improve shortness. Learning problems should be ameliorated by determining a child's optimal learning conditions. Behavior problems can usually be helped by counseling the family.History
The first description of a patient with the features of Noonan syndrome was made by Koblinsky in 1883, although it was not until the late 1960's that the condition became commonly referred to as Noonan syndrome.See also
External links
P.O.Box 145 Upperco, MD 21155, USA