Autosomal dominant tumor predisposition syndrome.

Synopsis

 cephalic anomalies

• macrocephaly
• sphenoid dysplasia
• Lisch nodules (iris hamartomas)
• glaucoma
• hypertelorism

 vascular anomalies

• renal artery stenosis

 skeletal anomalies

• scoliosis
• spina bifida
• pseudoarthrosis
• thinning of long bone cortex
• local bony overgrowth
• absent patellae

 cutaneous anomalies

• cafe-au-lait spots
• axillary freckling
• inguinal freckling

 cerebrospinal anomalies

• aqueductal stenosis
• hydrocephalus
• intrathoracic meningocele (#1681023#)

 tumor predisposition

• neurofibromas
• plexiform neurofibroma
• optic glioma
• meningioma
• hypothalamic tumor
• neurofibrosarcoma (malignant peripheral nerve sheath tumor MPNST)
• rhabdomyosarcoma
• duodenal carcinoid
• somatostatinoma
• parathyroid adenoma
• pheochromocytoma
• Wilms tumor
• ameloblastic fibroma
• ossifying fibroma of the bones

Etiology

 mutations in the NF1 gene encoding neurofibromin (MIM.162200)

• 50% of cases are caused by new mutations

References

 Costa RM, Silva AJ. Mouse models of neurofibromatosis type I: bridging the GAP. Trends Mol Med. 2003 Jan;9(1):19-23. PMID: #12524206#

 Gutmann DH. The neurofibromatoses: when less is more. Hum Mol Genet. 2001 Apr;10(7):747-55. PMID: #11257108#

 Reed N, Gutmann DH. Tumorigenesis in neurofibromatosis: new insights and potential therapies. Trends Mol Med. 2001 Apr;7(4):157-62. PMID: #11286939#