Neurofibromatosis 1

Question 1

What are the key clinical features of NF1?

Answer 1

(1) Cutaneous Neurofibromas, 98%,
(2) Cafe au Lait spots, 99%,
(3) Plexiform neuofibromas, 50%,
(4) Optic glioma, 15%,
(5) Scoliosis, 25–50%,
(6) Learning problems, 50–60%,
(7) Epilepsy, 12%,
(8) Malignant peripheral nerve sheath
tumors, 9%.
(9) Vasculopathy: dolichoectasia, aneurysm, steno-occlusive disease with moya moya appearance
(10) Sphenoid wing dysplasia (expansion of middle cranial fossa/superior orbital fissure with herniation of brain contents and proptosis)
(11) Can have abnormally high T2W signal (FASI/UBO) in the basal ganglia, cerebellum, brainstem

Question 2

Inheritance pattern and genetics of NF1?

Answer 2

Autosomal dominant. Mutation on long arm of chromosome 17 (17q11.2 encodes the protein neurofibromin). Defects in neurofibromin causes abnormalities in cell growth and proliferation => tumor formation

Question 3

What are the key clinical features of NF2?

Answer 3

(1) Vestibular Schwannoma, 95%,
(2) Cranial meningioma, 50%,
(3) Extramedullary spinal tumors (Schwannoma or meningioma), 80%,
(4) Intramedullary spinal cord or brainstem
tumors (ependymomas), 33%,
(5) Cataracts and retinal hamartoma, 80%,
(6) Skin tumors, 70% (subtle plaques, cutaneous tumors, subcut tumors)
(7) Seizures,
(8) Cranial nerve palsies.

Question 4

Inheritance pattern and genetics of NF2?

Answer 4

Autosomal dominant. Defect in Chromosome 22q12 encoding Merlin protein. It is characterized by multiple meningiomas, schwannomas, and ependymomas (MISME
syndrome). Half of all cases are spontaneous
mutations and a third of the new mutations
are mosaicisms. There is substantial
overlap between Neurofibromatosis type 2
and Schwannomatosis.