Noonan syndrome

Abstract

Noonan Syndrome (NS) is characterised by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The main facial features of NS are hypertelorism with down-slanting palpebral fissures, ptosis and low-set posteriorly rotated ears with a thickened helix. The cardiovascular defects most commonly associated with this condition are pulmonary stenosis and hypertrophic cardiomyopathy. Other associated features are webbed neck, chest deformity, mild intellectual deficit, cryptorchidism, poor feeding in infancy, bleeding tendency and lymphatic dysplasias. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Recently, mutations in the KRAS gene have been identified in a small proportion of patients with NS. A DNA test for mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. NS should be considered in all foetuses with polyhydramnion, pleural effusions, oedema and increased nuchal fluid with a normal karyotype. With special care and counselling, the majority of children with NS will grow up and function normally in the adult world. Management should address feeding problems in early childhood, evaluation of cardiac function and assessment of growth and motor development. Physiotherapy and/or speech therapy should be offered if indicated. A complete eye examination and hearing evaluation should be performed during the first few years of schooling. Preoperative coagulation studies are indicated. Signs and symptoms lessen with age and most adults with NS do not require special medical care.

Noonan Syndrome Presenting as Lymphoedema Precox

“…They lead to generalized lymphoedema, peripheral lymphoedema, pulmonary lymphangiectasia or intestinal lymphangiectasia. 8 Lymphangiographic studies have indicated that obstructed lymphatic drainage caused by congenital hypoplasia or absence of superficial lymphatic channels is a factor in the production of oedema in these patients. 9 The most common manifestation of the lymphatic dysplasia is dorsal limb lymphoedema, which generally disappears during childhood.…”

Mutation analysis of the SHOC2 gene in Noonan-like syndrome and in hematologic malignancies

“…Patients with Noonan syndrome occasionally develop juvenile myelomonocytic leukemia or leukemia. 2 Recently, the occurrence of ALL or non-Hodgkin's lymphoma has been reported in three patients with CFC syndrome. 5,19,20 The presence of leukocytosis in mutation-positive patients and the high expression of SHOC2 mRNA in PMN led us to look for possible SHOC2 mutations in patients with hematologic malignancies.…”

“…1,2 Noonan syndrome is a heterogeneous disease and overlaps phenotypically with Costello syndrome (MIM 218040) and cardio-facio-cutaneous (CFC) syndrome (MIM 115150). Costello syndrome is characterized by mental retardation, distinctive facial features, neonatal feeding difficulties, curly hair, loose skin, and hypertrophic cardiomyopathy and carries an increased risk of malignancy.…”

Unfoldomics of Human Genetic Diseases: Illustrative Examples of Ordered and Intrinsically Disordered Members of the Human Diseasome

“…Noonan syndrome is characterized by facial anomalies, postnatal growth retardation, webbing of the neck, pectus excavatum/carinatum, pulmonic stenosis and undescended testicles in boys. This syndrome is caused by the mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein [109].…”