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Neurofibromatosis, Type 1
		Uploaded: 2007-11-16, Updated: 2007-11-16

Chronic erosions/pits of the bone from the constant pressure of adjacent neurofibromas and schwannomas; the neural foramen of the spine can be widened due to the presence of a nerve root neurofibroma or schwannoma; also in NF-1, these is a generalized abnormality of the soft tissues, referred to as mesodermal dysplasia, which may cause maldevelopment of skeletal structures.

Focal scoliosis and/or kyphosis, the most common skeletal manifestation of NF-1, occurring in 20% of affected patients. Approximately one quarter of patients will require corrective surgery.
Bowing of a long bone with a tendency to fracture and not heal, yielding a pseudarthrosis. The most common bone to be affected is the tibia (causing congenital pseudarthrosis of the tibia or CPT). CPT occurs in 2-4% of individuals with NF-1.
Malformation of the facial bones or of the eye sockets (lambdoid suture defects, sphenoid dysplasia).
Unilateral overgrowth of a limb.

The most common complication in patients with NF-1 is cognitive and learning disability.
The cognitive problems are in approximately 80% of children with NF-1.
The most common cognitive problems are with perception, executive functioning and attention. ADHD has been shown to be present in approximately 38% of children with NF-1. Language, maths and motor deficits are also common. These cognitive problems have been shown to be stable into adulthood and do not get worse unlike some of the other physical symptoms of NF-1.

CLINICAL FEATURES
	Also called peripheral neurofibromatosis, or Recklinghausen's disease; One of the most common autosomal dominant genetic disorders; Accounts for 85% of NF patients; Incidence: 1/ 3000-4000, 50% due to spontaneous mutations; In familial cases, expressivity of the disorder is variable, but the penetrance is 100%.
GENETIC MUTATIONS
	The mutation rate in the NF1 gene (1/10,000) is among the highest known for any human gene. Gene location: 17q11.2; gene product: neurofibromin, a tumor suppressor.
DIAGNOSTIC CRITERIA
	At least 2 of the following features:
	Café au lait macules: at least six, > 5 mm in prepubertal children and > 1.5 cm in adults; Neurofibromas: at lease two of any type or one plexiform type; Multiple freckles (Crowe sign) in the axillary or inguinal region; Osseous lesion: sphenoid dysplasia, or thinning of long bone cortex, with or without pseudoarthrosis; Optic glioma; Iris hamartomas (Lisch nodules): two or more by slitlamp or biomicroscopy examination; A first-degree relative with NF1, as diagnosed by using the criteria above
PATHOLOGY FINDINGS
	Peripheral nervous system
	Neurofibromas: intraspinal, or peripheral (cutaneous, spinal nerve root and paraspinal nerve); Plexiform neurofibromas: the hallmark lesion of NF-1 is the plexiform neurofibroma. These lesions are composed of sheets of neurofibromatous tissue which may infiltrate and encase major nerves, blood vessels, and other vital structures.Associated with overlying hyperpigmentation or hypertrichosis. Rarely, rapid growth may occur and can be suggestive of malignant transformation; Malignant peripheral nerve-sheath tumors: approximately 2%.
	Central nervous system
	Optic glioma: usually pilocytic astrocytoma, classically bilateral; Dural ectasia: weakness of the dura leads to focal enlargement; Unidentified bright object (UBO): an intracranial lesion with increased signal on T2 MRI, typically found in the cerebellar peduncles, pons, midbrain, globus pallidus, thalamus, and optic radiations. Usually disappear by age 16, and may represent a focally degenerative bit of myelin.
	Skin
	Café-au-lait spots: present at birth or may appear over time, frequently increasing in size and number throughout childhood. In adults, café-au-lait spots tend to fade and may be less obvious; Axillary or inguinal freckles: rarely present at birth, but appear during childhood through adolescence; Cutaneous or subcutaneous neurofibroma.
	Skeletal system
	Chronic erosions/pits of the bone from the constant pressure of adjacent neurofibromas and schwannomas; the neural foramen of the spine can be widened due to the presence of a nerve root neurofibroma or schwannoma; also in NF-1, these is a generalized abnormality of the soft tissues, referred to as mesodermal dysplasia, which may cause maldevelopment of skeletal structures.
	Focal scoliosis and/or kyphosis, the most common skeletal manifestation of NF-1, occurring in 20% of affected patients. Approximately one quarter of patients will require corrective surgery. Bowing of a long bone with a tendency to fracture and not heal, yielding a pseudarthrosis. The most common bone to be affected is the tibia (causing congenital pseudarthrosis of the tibia or CPT). CPT occurs in 2-4% of individuals with NF-1. Malformation of the facial bones or of the eye sockets (lambdoid suture defects, sphenoid dysplasia). Unilateral overgrowth of a limb.
	Cognitive and learning abilities in NF-1
	The most common complication in patients with NF-1 is cognitive and learning disability. The cognitive problems are in approximately 80% of children with NF-1. The most common cognitive problems are with perception, executive functioning and attention. ADHD has been shown to be present in approximately 38% of children with NF-1. Language, maths and motor deficits are also common. These cognitive problems have been shown to be stable into adulthood and do not get worse unlike some of the other physical symptoms of NF-1.
	Other associated neoplasms
	Childhood MDS (myelodysplasia) and ANLL (often with monosomy 7 syndrome, 'juvenile myelomonocytic leukaemia'): risk, increased by X 200 to 500, is still low, as JMML is rare ; M>F; most often before the age of 5 yrs; no increased risk of leukemia in the adult Pheochromocytomas Rhabdomyosarcomas
REFERENCES
	AFIP, tumor of the central nervous system, series 4 http://www.emedicine.com/neuro/topic248.htm http://en.wikipedia.org/wiki/Neurofibromatosis_type_I