neurofibromatosis

definition

·      hamartomatous disorder of neural crest origin

·      can involve any organ system

aetiology

·      inherited disorder

·      most common single gene disorder found in humans

·      autosomal dominant with complete penetrance and variable expressivity

·      50% new spontaneous mutation rate

pathogenesis

·      of multiple cell origin

Neurogenic theory

·      disease develops through deviation in development of primitive neuroblast

·      affects its differentiation into other cells

·      esp. Schwann cell

Dysontogenic theory

·      tendancy to dysplasia of ectodermal and mesodermal tissue

clinical features
Type 1 (NF-1)

·      peripheral neurofibromatosis

·      von Recklinghausen’s disease

·      incidence 1 in 3 000

·      gene on long arm of chromosome 17

Diagnostic criteria

·      devised by National Institute of Health in 1987

·      require 2 or more of the following

1.   cafe au lait spots

·      6 or more

·      >5mm (prepubertal)

·      >15mm (postpubertal)

2.   freckling

·      axillary or inguinal

3.   neurofibromas

·      two or more neurofibromas of any sort OR

·      one plexiform neurofibroma

4.   optic glioma

5.   Leisch nodules

·      two or more

6.   distinctive osseous lesion

·      sphenoid dysplasia

·      thinning of long bone cortex with pseudarthrosis

7.   first degree relative with neurofibromatosis

·      parent, sibling or offspring

Neurofibromatosis 2

·      central neurofibromatosis

·      incidence 1 in 50 000

·      gene on long arm of chromosome 22

Features

·      two types

1.   multiple CNS involvement

·      neuraxial neoplasia

·      meningoneuroplasia

·      cranial schwannoma

2.   bilateral acoustic neuromas

·      isolated

·      dermal lesions unusual

SKIN manifestations
Cafe au lait spots

·      tan, maccular lesions

·      located in basal layer of epidermis

·      melanocytic in origin

·      often present in areas of skin not exposed to sun

·      present in <90% of NF-1

·      present in 20% of normal population

·      usually present by age 9

·      enlarge with age

·      become darker with puberty and pregnancy

·      said to have smooth edges

·      coast of California

·      cf. rough edges in fibrous dysplasia

·      coast of Maine

Nodules

·      fibroma molluscum

·      now considered to be dermal neurofibromas

·      manifestation of longstanding/ adult disease

·      usually elevated lesions with colour of normal skin

Naevi

·      hyperpigmentation

·      dark brown pigmented areas

·      may be isolated to one side of body

·      may be underlying plexiform neurofibroma

Plexiform neurofibroma

·      large neurofibroma

·      has ropey bag of worms feeling

·      extremely sensitive to touch

·      often overlying hyperpigmentation

·      can involve cord, canal, nerve roots

·      problems with

·      malignant transformation (10%)

·      local invasion

·      more aggressive if

·      overlying area of pigmentation

·      near midline

Elephantiasis

·      pachydermatocoele

·      large soft tissue mass

·      rough, raised villous type of skin hypertrophy

·      more common in adults

·      may be dysplasia of underlying bone

Verrucous hyperplasia

·      immense thickening and overgrowth of skin

·      associated with crevice formation, weeping and superficial infection

Axillary and inguinal freckling

·      2-3mm in diameter

·      in armpits, groin, inframammary area

SKELETAL manifestations
Scoliosis

Incidence

·      most common osseous defect

·      3% of scoliosis patients have NF

·      60% of NF patients have scoliosis

Aetiology

·      cause unknown

·      may be due to

·      osteomalacia

·      neurofibroma

·      endocrine disturbance

·      mesodermal dysplasia

Patterns

Dysplastic

·      usually upper thoracic area

·      short sharply angulated segment (4-6 bodies)

·      severe wedging  and rotation of apical vertebrae

·      scalloping of vertebral bodies

·      spindling of transverse processes

·      enlargement of foraminae

·      pencilling of apical ribs

·      adjacent neurofibroma

·      usually progressive

Nondysplastic

·      features of idiopathic scoliosis

·      left and right thoracic curves occur in equal number

Treatment

Dysplastic

·      usually progressive

·      bracing unsuccessful

·      posterior fusion procedure of choice

·      should have MRI to exclude intraspinal neurofibroma

Nondysplastic

·      same tendancy to progress as idiopathic form

·      same treatment protocol

·      higher incidence of pseudarthrosis

Kyphoscoliosis

Features

·      predominance of kyphosis

·      acute angulation

·      S-shaped rotatory scoliosis

·      high incidence of paraplegia

Treatment

·      anterior and posterior fusion

·      prolonged rigid immobilisation

·      very difficult to instrument

·      very high rate of pseudarthrosis post-operatively

Cervical spine

·      various lesions

·      atlanto-axial instability

·      vertebral body fusion and absence

·      increased incidence if thoracic curve present

Other spinal

·      due to

·      intraspinal neurofibromas (dumbbell tumours)

·      dural ectasia (saccular dilatations of dura)

·      may cause

·      intrathoracic meningocoele

·      scalloping of vertebral body

·      widening of intervertebral foramen

Disorders of bone growth

·      usually causes

·      hemihypertrophy

·      macrocephaly

·      bone shows

·      elongation

·      thickening

·      wavy irregularity of cortex

·      usually associated with changes in overlying soft tissue

·      haemangioma

·      elephantiasis

·      plexiform neuroma

Congenital bowing/ pseudarthrosis

·      most commonly affects tibia

·      anterolateral bow

·      can also affect

·      radius, ulnar, femur, clavicle, humerus

·      thought to be due to neurofibroma in bone

·      probably due to abnormality in overlying soft tissue

Bone erosion

·      from contiguous neurogenic tumours

·      may be pit or cyst

Subperiosteal bone proliferation

·      syn. subperiosteal calcifying haematoma

·      may be due to dysplasia of periosteum

ocular manifestations
Lisch nodules

·      pigmented iris hamartoma

·      present in 94% of patients with NF-1

Optic glioma
NEOPLASIA

·      common

·      most are neurogenic in origin

·      central or peripheral

·      neurogenic tumours include

·      optic giloma

·      astrocytoma

·      meningioma

·      neurofibroma

·      non-neurogenic tumours include

·      non-lymphocytic leukemia

·      Wilm's tumor

·      urogenital rhabdomyosarcoma

MISCELLANEOUS

·      short stature

·      mental retardation

·      learning difficulties

·      malignant hypertension

·      pectus excavatum