Noonan syndrome

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 clotting, 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. more...

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 features can vary greatly in patients with NS, thus diagnosis can often be delayed.

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 valves.

Noonan syndrome has been assigned OMIM number 163950 .

Manifestations by organ system

The most prevalent (common) signs are highlighted in bold with frequency listed in parentheses.

HEART —(2/3 of patients have a heart defect)

Pulmonary Valvular Stenosis —(50%)

Septal defects: atrial —(10%) or ventricular —(less common)

Heart murmur

Cardiomyopathy

GASTROINTESTINAL SYSTEM

Failure to thrive as an infant

Decreased appetite

Faddy eater

Digestive/Intestinal problems

Frequent or forceful vomiting

Swallowing difficulties

GENITO-URINARY SYSTEM

Cryptorchidism (undescended testicles) — (almost all males)

LYMPHATIC SYSTEM

Posterior cervical Hygroma (webbed neck)

Lymphedema (build-up of body fluid due to poor functioning of the lymphatic system)

DEVELOPMENTAL

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