Human pathology

Home page > D. Systemic pathology > Genetic and developmental anomalies > Noonan syndrome

Noonan syndrome

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.

Types

- Noonan syndrome type 1 (NS1) (PTPN11 at 12q24.1) (MIM.163950)
- Noonan syndrome type 2 (NS2) (MIM.605275)
- neurofibromatosis-Noonan syndrome (NF1 at 17q11.2) (MIM.162200)
- NS3 (MIM.609942)

Synopsis

- short stature
- webbed neck
- pectus excavatum
- cubitus valgus
- pulmonary valve stenosis
- patent foramen ovale
- characteristic face appearance
- cryptorchidism
- short stature (postnatal onset)
- failure to thrive in infancy
- specific growth curves are available
- triangular face with age
- low-set ears
- posteriorly rotated ears
- nerve deafness
- ptosis
- hypertelorism
- down-slanting palpebral fissures
- epicanthal folds
- myopia
- blue-green irides
- deeply grooved philtrum
- high peaks of upper lip vermilion border
- high arched palate - micrognathia
- dental malocclusion
- low posterior hairline
- webbed neck
- cystic hygroma
- congenital heart defect
- atrial septal defects
- ventricular septal defects
- pulmonic stenosis
- patent ductus arteriosus
- shield chest
- pectus carinatum superiorly
- pectus excavatum inferiorly
- occasional hypogonadism
- cryptorchidism
- male infertility in individuals with bilateral cryptorchidism
- vertebral abnormalities
- cubitus valgus
- clinodactyly
- brachydactyly
- blunt fingertips
- wooly-like consistency of hair
- lmphedema
- aticulation difficulties
- mental retardation (25%)
- megakaryocytic thrombocytopenia
- Von Willebrand disease
- bleeding tendency

NEOPLASIA :
- Malignant schwannoma

Laboratory

- Partial deficiency of factor XI:C
- Partial deficiency of factor XII:C
- Partial deficiency of factor XIII:C
- Thrombocytopenia

- rare autoimmune diseases

- central giant cell granuloma (giant cell granuloma of the jaws) (9660063)

Etiology

This autosomal dominant disease is caused mainly by mutations in the protein tyrosine phosphatase, nonreceptor-type, 11 gene (PTPN11) (MIM.176876).

- germline mutations in

References

- van der Burgt I. Noonan syndrome. Orphanet J Rare Dis. 2007 Jan 14;2:4. PMID: 17222357

- Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007 Apr;7(4):295-308. PMID: 17384584

Keywords