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