Neurofibromatosis 1

Noonan Syndrome

Mutation

NF1

PTPN11

SOS1, RAF1, KRAS.

Inheritance pattern

AD

AD

Clinical features

Neurofibromas

Lisch nodules

Axillary freckling

Plexiform neurofibroma

> 6 Café-au-lait macules

Skeletal abnormalities; as scoliosis, dysplasia of sphenoid

bones and thinning of the long bones with and

without pseudoarthrosis.

Optic glioma.

Learning difficulties and attention deficit disorder occurs in up to 50%.

Short stature

Facial: triangular face; ear abnormalities: low-set posteriorly rotated ears and thick helix; eye abnormalities: ptosis, hypertelorism, epicanthal folds, down-slanting palpebral fissures,

strabismus, proptosis, myopia and nystagmus; deeply grooved philtrum with high peaks of upper lip vermilion border; neck abnormalities: short or webbed neck.

Cardiac: congenital heart defect (50–75%); pulmonary valve stenosis (50%), hypertrophic cardiomyopathy.

Chest: pectus carinatum/ excavatum, broad thorax.

Mental retardation

Cryptorchidism

Lymphatic dysplasia

Cancer risk

Increased:

neurofibrosarcoma, astrocytoma, pheochromocytoma and juvenile myelomonocytic leukemia.

Increased, but in low percentage:

juvenile myelomonocytic leukemia and multiple giant cell lesions