Neurofibromatosis

growth rate of plexiform NF

highly variable periods of rapid growth and quiescence

Features of Noonan syndrome

hypertelorism, ptosis, downsloping palpebral fissures, low set, posteriorly rotated ears, webbed neck, pectus deformities, and short stature. Over 50% of children with Noonan syndrome have cardiovascular disease, most commonly pulmonary valve stenosis mutation in PTN11

Possible new treatment of plexiform NF

imatinib sirolimus

what are the bony abnormalities of NF

sphenoid dysplasia - results in poor formation of the wall of the orbit dysplasia of long bones & bowing - usually tibia scoliosis is most common skeletal manifestation

what happens if NF1 is deleted.?

Facial dysmorphism, MR early NFs and plexiform NFs

other diseases with PTPN11 mutations

LEOPARD NOONAN

what are lisch nodules?

slightly raised well-circumscribed melanocytic hamartomas of the iris thought to be virtually pathognomonic of NF-1 do not cause functional impairment

What are the types of NF?

1. von Recklinghausen disease 2. bilateral vestibular schwannomas 3. segmental 4. Legius Spred 1 5. schwannomatosis

what percentage of children with NF have optic tumors

15% but only half are symptomatic more females greatest risk in first six years of life

A patient has the clinical diagnosis of NF-2 if one of the following criteria is present:

Bilateral vestibular schwannomas First degree family relative with NF-2 and unilateral vestibular schwannomas or any twoa: meningioma, schwannoma, glioma, neurofibroma, or posterior subcapsular lenticular opacities Unilateral vestibular schwannoma and any twoa: meningioma, schwannoma, glioma, neurofibroma, or posterior subcapsular lenticular opacities Multiple meningiomas (two or more) and unilateral vestibular schwannoma and any twoa: schwannoma, glioma, neurofibroma, cataract

Ddx of multiple CALms

Most Likely Neurofibromatosis type-1 Neurofibromatosis type-2 Familial café-au-lait spots (consider Legius syndrome) LEOPARD syndrome (multiple lentingines syndrome) Less Likely Tuberous sclerosis Fanconi anemia Multiple endocrine neoplasia type 2B Bannayan-Riley-Ruvalcaba syndrome McCune-Albright syndrome (polyostotic fibrous dysplasia) Bloom syndrome Ataxia-telangiectasia

diagnostic criteria for NF

Need two or more 6 CALMS >5 mm in greatest diameter in prepubertal individuals, and over 15 mm in postpubertal individuals Two or more neurofibromas of any type or one plexiform neurofibroma Freckling in the axillary or inguinal regions Optic glioma Two or more iris Lisch nodules A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex with or without pseudarthrosis A first-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria

what are neurofibromas made of

Schwann cells, mast cells, fibroblasts, and perineural cells, are benign nerve sheath tumors that appear as discrete masses arising from peripheral nerves

what is Legiuss syndrome

Spred 1 autosomal dominant Café au lait, intertriginous freckles macrocephaly

symptoms of optic glioma

afferent papillary defect, optic nerve atrophy, papilledema, strabismus, or defects in color vision

where is NF1 located

chromosome 17 encodes neurofinromin

where is NF 2 and what does it encode

chromosome 22 schwannomin aka merlin

cancer associated with NF

especially in females CNS tumors pheochromocytoma peripheral nerve sheath tumors- arise from plexiform NF CML and ALL - JXGs

Eye findings in NF 2

juvenile posterior subcapsular cataracts retinal hamartomas optic nerve sheath meningiomas

what is RAS?

membrane-bound protein that requires farnesylation addition of C15 isoprenoid to a cysteine

patients with NF 2 at risk of developing

multiple meningiomas, schwannomas, gliomas, and neurofibromas throughout neural axis. juvenile posterior subcapsular cataracts

Schwannomatosis

multiple schwannomas without other manifestations of NF2 caused by mutations in SMARCB1/INI1

what is a plexiform neurofibromas

nerve sheath tumor involving single or multiple nerve fascicles wormy sensation on palpation

IQ in NF

only 5-10 points lower than average

what causes segmental NF

post-conceptual mutation in NF1

Chiasmal tumors associated with

precocious puberty

when do plexiform neurofibromas appear

usually present at birth