2. Introduction
• First described by Frederich von Recklinghausen in 1882
• NF1 is an inherited disorder that affects about one in 2500 to one in 3000 people world wide,
irrespective of sex or ethnic origin.
• Prone to develop benign and malignant tumours of the CNS and peripheral nervous system, in
addition to malignant diseases affecting other parts of the body.
Lammert M, Friedman JM, Kluwe L, Mautner VF. Prevalence of neurofi bromatosis 1 in German children at elementary school enrollment. Arch Dermatol 2005; 141: 71–74.
Huson SM, Harper PS, Compston DA. Von Recklinghausen neurofi bromatosis: a clinical and population study in south-east Wales. Brain 1988; 111: 1355–81.
Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofi bromatosis type 1 revisited. Pediatrics 2009; 123: 124–33.
3. Commonly Associated Tumors
Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. The Lancet Neurology. 2014 Aug 1;13(8):834-43.
4. Diagnostic Criteria
Anon. National Institutes of Health Consensus Development Conference Statement: neurofi bromatosis—Bethesda, MD, USA, July 13–15, 1987. Neurofi bromatosis 1988; 1: 172–78.
5. Genetics
• Germline mutation in the NF1 tumour-suppressor gene.
• Spontaneous mutation.
• Individuals with NF1 microdeletions tend to develop neurofibromas at an earlier age, have a
lower mean IQ, manifest abnormal facial features, and are at increased risk of developing
malignant peripheral nerve-sheath tumours.
• Genetic testings
Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. The Lancet Neurology. 2014 Aug 1;13(8):834-43.
6. Clinical Features
• Café au lait, freckles, lisch nodules
Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 2007; 44: 81–88.
Friedman JM. Neurofi bromatosis 1: clinical manifestations and diagnostic criteria. J Child Neurol 2002; 17: 548–54.
7. Clinical Features
• Neurofibromas are benign Schwann-cell tumours composed not only of neoplastic Schwann
cells but also of non-neoplastic fi broblasts, mast cells, macrophages, endothelial cells, pericytes,
and perineural cell
Le LQ, Parada LF. Tumor microenvironment and neurofi bromatosis type I: connecting the GAPs. Oncogene 2007; 26: 4609–16.
Munchhof AM, Li F, White HA, et al. Neurofi broma-associated growth factors activate a distinct signaling network to alter the function of neurofi bromin-defi cient endothelial cells. Hum Mol Genet 2006; 15: 1858–69.
Yang FC, Ingram DA, Chen S, et al. Neurofi bromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/– mastcells. J Clin Invest 2003; 112: 1851–61.
Yang FC, Ingram DA, Chen S, et al. Nf1-dependent tumors require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow. Cell 2008; 135: 437–48.
8. Clinical Features
Skeletal abnormalities:
- Osteopenia
- Scoliosis
- Sphenoid wing dysplasia
- Congenital tibial dysplasia
- Pseudarthrosis
Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. The Lancet Neurology. 2014 Aug 1;13(8):834-43.
9. Clinical Features
Cardiovascular abnormalities
• Congenital heart disease
• Vasculopathy
• Hyper tension
Neurocognitive defi cits
• Learning difficulties can include
visuospatial and visuomotor deficits,
language disorders, and fine and gross
motor deficiencies
• Furthermore, attention-deficit hyperactivity
disorder, autism spectrum disorders,
behavioural abnormalities
• zpsychosocial issues
Tedesco MA, Di Salvo G, Natale F, et al. The heart in neurofi bromatosis type 1: an echocardiographic study. Am Heart J 2002; 143: 883–88.
Acosta MT, Gioia GA, Silva AJ. Neurofi bromatosis type 1: new insights into neurocognitive issues. Curr Neurol Neurosci Rep 2006; 6: 136–43.
10. Clinical Features
Nervus system tumors
- Optic pathways and brainstem gliomas
- Glioblastomas
- Malignant peripheral nerve sheath tumours
(Neurofibrosarcomas or neurogenic sarcomas)
Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. The Lancet Neurology. 2014 Aug 1;13(8):834-43.
11. Clinical Features
Non nervous system tumors
- Gastrointestinal stromal tumours
- Breast cancers
- Leukaemia and lymphoma
- Phaeochromocytoma
- Duodenal carcinoids
- Rhabdomyosarcomas
12. Summary
• Inherited disorder
• Prone to develop benign and malignant tumours of the CNS and peripheral nervous system, in
addition to malignant diseases affecting other parts of the body
• Café ua lait ; lisch nodules
• Management: multidisciplinary approach
