Neurofibromatosis Disease

BASICS

DESCRIPTION

The most common of the neurocutaneous syndromes (phakomatosis), consisting of Neurofibromatosis Type 1 (1 in 4,000) and Neurofibromatosis Type 2 (1 in 50,000). Although named similarly, and both autosomal dominant disorders, they are two distinctly different conditions with genes now identified on two separate chromosomes.

Type 1 (NF 1) is also known as von Recklinghausen disease
Type 2 (NF 2) as bilateral acoustic neurofibromatosis
System(s) affected: Nervous, Skin/Exocrine, Musculoskeletal
Genetics:
- NF1: autosomal dominant inheritance. Nearly 50% of cases are attributed to new mutations. The NF1 gene mapped to chromosome 17. Prenatal diagnosis possible.
- NF2: autosomal dominant inheritance. The NF2 gene mapped on chromosome 22.
Incidence/Prevalence in USA: NF 1 = 1/4,000; NF 2 = 1/50,000
Predominant age: N/A
Predominant sex: Male = Female

SIGNS AND SYMPTOMS

NF1: Two or more of the following:
- Six or more café-au-lait macules measuring 5 mm or more in prepubertal individuals or 15 mm or more in adults (97%)
- Two or more neurofibromata or plexiform neurofibroma (15%)
- Axillary or inguinal freckling (91%)
- Two or more Lisch nodules (30%)
- Optic glioma (4%)
- Characteristic osseous lesions such as sphenoid dysplasia, long bone cortical thinning, ribbon ribs, angular scoliosis (6%)
- First degree relative with NF1, according to above criteria
NF2: When one or more present, diagnosis is likely:
- Bilateral vestibular schwannomas
- Family history of NF2, plus unilateral 8th nerve mass or family history and any two of the following: neurofibroma, meningioma, glioma, schwannoma, and juvenile posterior subcapsular lenticular opacity

CAUSES

Congenital

RISK FACTORS

Family history

DIAGNOSIS

LABORATORY

N/A
Drugs that may alter lab results: N/A
Disorders that may alter lab results: N/A

PATHOLOGICAL FINDINGS

NF1: Generalized disorder of cells of neural crest origin

SPECIAL TESTS

N/A

IMAGING

N/A

DIAGNOSTIC PROCEDURES

NF1:
- Dictated by findings and clinical evaluation
- Slit lamp ocular exam
- Radiology of skull and spine
- Psychological testing
- Diagnostic criteria: two or more of the following:
  - Six or more café-au-lait spots measuring 5 mm or more in prepubertal individuals or 15 mm or more in adults (97%)
  - Two or more neurofibromata or plexiform neurofibroma (15%)
  - Axillary or Inguinal freckling (91%)
  - Two or more Lisch nodules (30%)
  - Optic glioma (4%)
  - Characteristic osseous lesions such as sphenoid dysplasia, long bone cortical thinning, ribbon ribs, angular scoliosis (6%)
- First degree relative with NF1, according to above criteria
NF2:
- Clinical examination: skin, eye, and hearing
- Audiologic evaluation: brain stem evoked response (BAER)
- Radiologic examination: MRI of head
- When one or more of the following are present, the diagnosis of NF2 is likely:
  - Bilateral vestibular schwannomas
  - Family history of NF2, plus unilateral 8th nerve mass or family history and any two of the following: neurofibroma, meningioma, glioma, schwannoma, and juvenile posterior subcapsular lenticular opacity

TREATMENT

APPROPRIATE HEALTH CARE

Outpatient

GENERAL MEASURES

Access to patient support groups
Referral of patient to National NF Organization
NF1:
- General outpatient follow-up of symptomatic patients for early identification of complications
- Periodic exams with particular attention to CNS findings and close attention to any masses or focally arising "new" pain
- Referral for psychosocial issues of family and affected individuals
- Educational intervention for children with learning disabilities or ADHD (40%)
NF2:
- Annual neurologic examination
- Annual ophthalmologic exam
- Annual hearing examination or more frequently as necessitated
- Hearing augmentation as needed
- Speech therapy as needed
- Counseling and education regarding insidious problems associated with hearing loss, balance, or sense of direction

SURGICAL MEASURES

NF1: Surgical treatment if indicated for scoliosis, plexiform neurofibromata, or malignancy
NF2: Excision of tumor as indicated

ACTIVITY

NF2: Caution advised in swimming, diving, or climbing heights

DIET

No restrictions

PATIENT EDUCATION

Genetic counseling and patient education regarding future complications and decisions about family planning

FOLLOW UP

PREVENTION/AVOIDANCE

Genetic counseling

POSSIBLE COMPLICATIONS

NF1:
- Disfigurement: skin neurofibromata develop primarily on exposed areas
- Scoliosis: common; most cases mild
- CNS: A large head is common but rarely associated with hydrocephalus. Optic glioma or other CNS tumors arise usually during childhood (5-10%)
- Learning disability: common; often diagnosed upon entering school. May be associated with attention deficit hyperactivity disorder (ADHD)
- Rare Complications:
  - Mental retardation
  - Epilepsy
  - Hypertension
  - Variable onset of puberty
  - Slightly higher risk for malignancy (e.g., Wilms', leukemia, rhabdomyosarcoma)

EXPECTED COURSE AND PROGNOSIS

NF1: Variable; most patients have a mild expression and lead normal lives
NF2: Variable

MISCELLANEOUS

ASSOCIATED CONDITIONS

N/A

AGE-RELATED FACTORS

Pediatric: External stigmata subtle or absent in very young children
Geriatric: Cutaneous lesions and tumors increase in size and number with age
Others: N/A

PREGNANCY

Genetic counseling

OTHER NOTES

N/A

ABBREVIATIONS

N/A

Clinical Investigations

ROLE OF HOMOEOPATHY

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