I. Epidemiology

  1. Autosomal dominant
    1. Chromosome region 17q11.2
    2. Parent with NF has 50% of transmission per birth
  2. Incidence
    1. NF-1: 1 in 4000
    2. NF-2: 1 in 50,000

II. Pathophysiology

  1. Disorder of neural crest differentiation

III. Diagnostic Criteria: NF-1 (any 2 of below present)

  1. Cafe-Au-Lait Spots (6 or more in 100% of cases)
    1. Pre-Puberty: >5 mm greatest diameter
    2. Post-Puberty: >15 mm greatest diameter
  2. Axillary or inguinal Freckles (2-3 mm diameter)
  3. Iris Lisch Nodules (2 or more)
    1. Hamartomas on iris (Slit Lamp exam)
    2. Present in half by kindergarten, 100% by age 21 years
  4. Optic Glioma (Optic Nerve benign tumor)
    1. Pupil dilates on response to bright light
  5. Neurofibromas (2 or more)
    1. Small, Rubbery, purple skin lesions
  6. Bone abnormalities (one of associated conditions)
    1. Scoliosis (most common)
    2. Sphenoid dysplasia
    3. Long bone cortical thinning
  7. First degree relative with NF-1

IV. Diagnostic Criteria: NF-2 (one of the following)

  1. Bilateral Cranial Nerve 8 Acoustic Neuromas
  2. First degree relative with NF-2 and one criteria below:
    1. Unilateral Acoustic Neuroma
    2. Neurofibroma (much less common in NF-2)
    3. Meningioma
    4. Glioma
    5. Schwannoma
    6. Posterior subcapsular lenticular opacity

V. Associated Conditions

  1. NF-1
    1. Intracranial low grade gliomas and hamartomas
    2. Learning disabilities (e.g. ADHD)
    3. Speech abnormalities
    4. Seizure disorder
    5. Macrocephaly
    6. Hydrocephalus (rare)
    7. Cerebrovascular Disease (Moyamoya Disease)
    8. Hypertension
      1. Associated with Renal Artery Stenosis
      2. NF-1 also associated with Pheochromocytoma
    9. Precocious Puberty
    10. Malignancies (e.g. Leukemia, Wilms' Tumor)
    11. CNS tumors (e.g. meningiomas, astrocytomas)
  2. NF-2
    1. CNS tumors (e.g. Schwann cell, glioma, meningioma)

VI. Monitoring

  1. Detailed history and physical periodically
  2. Pediatric Ophthalmology annually

VII. References

  1. Behrman (2000) Nelson Textbook of Pediatrics, p. 1835
  2. Debella (2000) Pediatrics 105:608-14 [PubMed] (or open in [QxMD Read])
  3. Lynch (2002) Neurol Clin 20(3):841-65 [PubMed] (or open in [QxMD Read])

Images: Related links to external sites (from Google)

Ontology: Neurofibromatosis 1 (C0027831)

Definition (NCI) Type 1 (peripheral) neurofibromatosis (von Recklinghausen's disease), is the most common type of neurofibromatosis. It is characterized clinically by cutaneous and subcutaneous tumors with patches of hyperpigmentation. The hyperpigmented skin areas, are present from birth and found anywhere on the body surface. They can vary markedly in size and color. The dark brown areas are called cafe-au-lait spots. The multiple cutaneous and subcutaneous tumors are nerve sheath neoplasms, called neurofibromas. They can develop anywhere along the peripheral nerve fibers. Neurofibromas can become quite large, causing a major disfigurement, eroding bone, and compressing various peripheral nerve structures. Type 1 neurofibromatosis has dominant inheritance, with a gene locus on the proximal long arm of chromosome 17.
Definition (NCI) A rare genetic condition that causes brown spots and tumors on the skin, freckling in skin areas not exposed to the sun, tumors on the nerves, and developmental changes in the nervous system, muscles, bone, and skin.
Definition (MSH) An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS).
Concepts Neoplastic Process (T191)
MSH D009456 , C538607
ICD9 237.71
ICD10 Q85.01
SnomedCT 92824003, 81669005
English Neurofibromatosis 1, Neurofibromatosis, Peripheral, NF 1, Neurofibromatosis, Peripheral, NF1, Recklinghausen Disease of Nerve, Recklinghausen's Disease of Nerve, Recklinghausens Disease of Nerve, von Recklinghausen Disease, von Recklinghausen's Disease, von Recklinghausens Disease, Neurofibromatosis, type 1 (von Recklinghausen's disease), PHAKOMATOSIS RECKLINGHAUSEN, RECKLINGHAUSEN DISEASE, Von Recklinghausen's Disease, Von Recklinghausen's disease, neurofibromatosis type 1, neurofibromatosis type 1 (NF1), VON RECKLINGHAUSEN DISEASE, NF1, NEUROFIBROMATOSIS, TYPE I, RECKLINGHAUSENS DIS OF NERVE, NEUROFIBROMATOSIS A 01, RECKLINGHAUSEN DIS OF NERVE, VON RECKLINGHAUSENS DIS, VON RECKLINGHAUSEN DIS, [M]Von Recklinghausen's dis, Von Recklinghausen's dis, Recklinghausen's neurofibromatosis, type I neurofibromatosis (diagnosis), neurofibromatosis type I (von Recklinghausen's disease), von Recklinghausen's disease, type I neurofibromatosis, Von Recklinghausen's disease (of nerve), NF1 (Neurofibromatosis 1), Neurofibromatosis Type 1, Neurofibromatosis, Type 1, Type 1 Neurofibromatosis, Type 1, Neurofibromatosis, Neurofibromatosis I, I, Neurofibromatosis Type, Neurofibromatoses, Type I, Neurofibromatosis Type I, Neurofibromatosis, Type I, Type I Neurofibromatoses, Type I, Neurofibromatosis, Neurofibromatoses, Peripheral, Neurofibromatosis, Peripheral, Peripheral Neurofibromatoses, Peripheral Neurofibromatosis, Neurofibromatosis type I, NEUROFIBROMATOSIS, PERIPHERAL TYPE, Neurofibromatosis 1 [Disease/Finding], Recklinghausen's Disease, von recklinghausen's disease, neurofibromatosis 1, recklinghausen disease, von recklinghausen disease, neurofibromatosis i, von recklinghausens disease, disease recklinghausens, neurofibromatosis type i, recklinghausen's disease, Recklinghausen's disease, Von Recklinghausen disease, Recklinghausen Disease, Nerve, Neurofibromatosis type 1, [M]Von Recklinghausen's disease, Neurofibromatosis, type 1, Clinical von Reclinghausen's disease, Neurofibromatosis, type 1 (disorder), disease; Von Recklinghausen, Von Recklinghausen; disease, Von Recklinghausen Disease, Neurofibromatosis, type 1 [von Recklinghausen's disease]
Dutch ziekte van Von Recklinghausen (zenuw), neurofibromatose, type 1 (ziekte van von Recklinghausen), Von Recklinghausen; ziekte, ziekte; Von Recklinghausen, Neurofibromatose 1, Neurofibromatose, 1, Perifere neurofibromatose, Von Recklinghausen, ziekte van, Ziekte van Von Recklinghausen
French Neurofibromatose de type 1 (maladie de von Recklinghausen), Maladie de Von Recklinghausen (nerf), NF-1 (Neurofibromatose de type 1), Maladie de von Recklinghausen, Neurogliomatose, Neurofibromatose de type 1, Neurofibromatose de type I, Gliofibromatose de Recklinghausen, Maladie de Recklinghausen, NF1 (Neurofibromatose de type 1)
German Von Recklinghausen-Krankheit (des Nervs), Neurofibromatose, Typ 1 (von Recklinghausenkrankheit), NEUROFIBROMATOSE A 01, Neurofibromatose 1, Neurofibromatose, periphere, NF1, Recklinghausenkrankheit, Nerven, Periphere Neurofibromatose, von-Recklinghausen-Krankheit
Italian Malattia di Von Recklinghausen (nervosa), Neurofibromatosi tipo I [malattia di von Recklinghausen], Neurofibromatosi 1
Portuguese Neurofibromatose tipo 1 (doença de von Recklinghausen), Doença de von Recklinghausen (dos nervos), Doença de Recklinghausen, Doença de von Recklinghausen, Doença Nervosa de Recklinghausen, Doença Neural de Recklinghausen, Neurofibromatose 1, Neurofibromatose Periférica
Spanish Neurofibromatosis de tipo 1 (enfermedad de von Recklinghausen), Enfermedad de Von Recklinghausen (de nervio), enfermedad de von Recklinghausen clínica, enfermedad de von Reclinghausen clínica, neurofibromatosis, tipo 1 (trastorno), neurofibromatosis, tipo 1, Enfermedad de von Recklinghausen, Enfermedad Nerviosa de Recklinghausen, Neurofibromatosis 1, Neurofibromatosis de Recklinghausen, Neurofibromatosis Periférica, Neurofibromatosis Periferica
Japanese フォンレックリングハウゼン病, 神経線維腫症、1型(フォンレックリングハウゼン病), フォンレックリングハウゼンビョウ, シンケイセンイシュショウ1ガタフォンレックリングハウゼンビョウ, 神経線維腫症-末梢-NF-1, NF1末梢神経線維腫症, Recklinghausen病1型, 神経線維腫症-NF1末梢, 神経レックリングハウゼン病, レックリングハウゼン病-1, Recklinghausen病-神経, レックリングハウゼン病1型, Recklinghausen病-1, 神経Recklinghausen病, レックリングハウゼン病-神経, 神経線維腫症1, NF-1末梢神経線維腫症, 神経線維腫症1型
Swedish Neurofibromatos 1
Czech Recklinghausenova neurofibromatóza, neurofibromatóza 1, Neurofibromatóza typu 1 (von Recklinghausenova nemoc), Von Recklinghausenova nemoc (nervu)
Finnish Neurofibromatoosi 1
Russian NEIROFIBROMATOZ 1, NEIROFIBROMATOZ PERIFERICHESKII NF1, NEIROFIBROMATOZ TIPA I, REKLINGAUZENA BOLEZN' NERVA, НЕЙРОФИБРОМАТОЗ 1, НЕЙРОФИБРОМАТОЗ ПЕРИФЕРИЧЕСКИЙ NF1, НЕЙРОФИБРОМАТОЗ ТИПА I, РЕКЛИНГАУЗЕНА БОЛЕЗНЬ НЕРВА
Polish Nerwiakowłókniakowatość typ 1, Choroba Recklinghausena, Neurofibromatoza 1, Włókniakonerwiakowatość obwodowa
Hungarian Von Recklinghausen-betegség (ideg), Neurofibromatosis, I típus (von Recklinghausen-betegség)

Ontology: Neurofibromatoses (C0162678)

Definition (NCI) An autosomal dominant hereditary neoplastic syndrome. Two distinct clinicopathological entities are recognized: neurofibromatosis type 1 and neurofibromatosis type 2. Neurofibromatosis type 1 is associated with the presence of cafe-au-lait cutaneous lesions, multiple neurofibromas, malignant peripheral nerve sheath tumors, optic nerve gliomas, and bone lesions. Neurofibromatosis type 2 is associated with the presence of schwannomas, meningiomas, and gliomas.
Definition (MEDLINEPLUS)

Neurofibromatosis is a genetic disorder of the nervous system. It mainly affects how nerve cells form and grow. It causes tumors to grow on nerves. You can get neurofibromatosis from your parents, or it can happen because of a mutation (change) in your genes. Once you have it, you can pass it along to your children.

There are three types of neurofibromatosis:

  • Type 1 (NF1) causes skin changes and deformed bones and usually starts at birth.
  • Type 2 (NF2) causes hearing loss, ringing in the ears and poor balance. It often starts in the teen years.
  • Schwannomatosis causes intense pain. It is the rarest type.

There is no cure. Treatment is aimed at controlling symptoms. Depending on the type of disease and how bad it is, treatment may include surgery to remove tumors, radiation therapy and medicines.

NIH: National Institute of Neurological Disorders and Stroke

Definition (MSH) A group of disorders characterized by an autosomal dominant pattern of inheritance with high rates of spontaneous mutation and multiple neurofibromas or neurilemmomas. NEUROFIBROMATOSIS 1 (generalized neurofibromatosis) accounts for approximately 95% of cases, although multiple additional subtypes (e.g., NEUROFIBROMATOSIS 2, neurofibromatosis 3, etc.) have been described. (From Neurochirurgie 1998 Nov;44(4):267-72)
Definition (CSP) group of disorders characterized by an autosomal dominant pattern of inheritance with high rates of spontaneous mutation and multiple neurofibromas or neurilemmomas; neurofibromatosis 1 (generalized neurofibromatosis) accounts for approximately 95% of cases, although multiple additional subtypes (e.g., neurofibromatosis 2, neurofibromatosis 3, etc.) have been described.
Concepts Neoplastic Process (T191)
MSH D017253
ICD9 237.70, 237.7
ICD10 M9540/1 , Q85.00
SnomedCT 154642000, 81669005, 19133005
English Neurofibromatosis, NEUROFIBROMA, MULTIPLE, NEUROFIBROMATOSIS, Neurofibromatosis, NOS, Neurofibromatosis, unspecified, Neurofibromatoses, Neurofibromatosis NOS, neurofibromatosis (diagnosis), neurofibromatosis, Neurofibromatosis (disorder), Multiple Neurofibroma, Multiple Neurofibromas, Neurofibroma, Multiple, Neurofibromas, Multiple, Neurofibromatosis Syndrome, Neurofibromatosis Syndromes, Syndrome, Neurofibromatosis, Syndromes, Neurofibromatosis, Neurofibromatoses [Disease/Finding], neurofibromatosi, neurofibromatosys, multiple neurofibromatosis, neurofibromatose, Multiple neurofibromatosis, Neurofibromatosis syndrome, NF - Neurofibromatosis, [M]Multiple neurofibromatosis, [M]Neurofibromatosis NOS, Clinical neurofibromatosis, Neurofibromatosis (morphologic abnormality), Neurofibromatosis syndrome (disorder), neurofibromatoses
Dutch neurofibromatose, niet-gespecificeerd, neurofibromatose, Neurofibromatose
French Neurofibromatose, non précisée, Neurofibromatose, Neurofibromatoses, Neurofibromes multiples
German Neurofibromatose, unspezifisch, Neurofibromatose, Neurofibromatosen
Italian Neurofibromatosi, non specificato, Neurofibromatosi
Portuguese Neurofibromatose NE, Neurofibromatose Tipo 3, Neurofibromatose, Neurofibromatoses
Spanish Neurofibromatosis no especificada, Neurofibromatosis, neurofibromatosis (anomalía morfológica), neurofibromatosis clínica, neurofibromatosis múltiple, neurofibromatosis, SAI, neurofibromatosis, síndrome de neurofibromatosis (trastorno), síndrome de neurofibromatosis
Japanese 神経線維腫症、詳細不明, シンケイセンイシュショウショウサイフメイ, シンケイセンイシュショウ, 神経線維腫症, 神経鞘腫症
Swedish Neurofibromatoser
Czech neurofibromatózy, Neurofibromatóza, blíže neurčená, Neurofibromatóza
Finnish Neurofibromatoosit
Russian NEIROFIBROMATOZY, NEVROFIBROMATOZ, NEIROFIBROMATOZ, НЕВРОФИБРОМАТОЗ, НЕЙРОФИБРОМАТОЗ, НЕЙРОФИБРОМАТОЗЫ
Croatian NEUROFIBROMATOZE
Polish Neurofibromatozy, Nerwiakowłókniakowatość
Hungarian Neurofibromatosis, nem meghatározott, Neurofibromatosis