Noonan Syndrome

Question 1

Inheritance of Noonan syndrome

Answer 1

Autosomal dominant

Question 2

Another name

Answer 2

Male Turner’s

Question 3

Karyotype

Answer 3

Normal

Question 4

Abnormal Chromosome & Gene

Answer 4

Chromosome 12

Gene: PTPN11 (50% and most common)

Encodes: Protein tyrosine phosphatase non-receptor type 11

Also:Chromosome 15, Gene MAP2K1, Encodes mitogen-activated protein kinase kinase 1 (member of MAPK kinase pathway) & several others

Question 5

Defected genes ( = Associated genes)

Answer 5

PTPN11, MAP2K1, SOS1, RADF1 and KRAS

50% have defect in PTPN11

Question 6

Protein encoded by PTPN11

Answer 6

Protein tyrosine phosphatase non-receptor type 11

(other involved genes encode proteins that are part of MAPK kinase pathway)

Question 7

Similar features between Turner syndrome and Noonan syndrome

Answer 7

Short stature

Webbed neck

Widely spaced nipples

Pectus carinatum

Pectus excavatum

Cubitus valgus

Question 8

Facial features of Noonan syndrome (absent in Turner)

Answer 8

Triangular shaped face

Low-set ears (and/or posteriorly rotated)

Ptosis

Question 9

Blood defect in Noonan syndrome (Absent in Turner)

Answer 9

Coagulation disorder (factor 11C deficiency common)

30% has factor 11C, 12C, 8C deficiencies

Von Willibrand disease

Juvenile myelomonocytic leukaemia (rarely)

Thrombocytopenia

(Factor 11 & 8 deficiency can be haemophilia)

Question 10

Cardiac defect specifically in Noonan syndrome

Answer 10

Pulmonary valve stenosis (more common)

Hypertrophic cardiomyopathy

Septal defects: ASD, VSD

Branch pulmonary artery stenosis

Question 11

Cardiac defect in Noonan syndrome & Turner syndrome

Answer 11

Noonan syndrome:

• Pulmonary valve stenosis

Turner syndrome

• Bicuspid aortic valve 15%
• Coarctation of aorta 5-10%

Question 12

Intelligence

Answer 12

Mild intellectual disability in 30%