NEUROFIBROMATOSIS{ PHAKOMATOSIS }

NEUROFIBROMATOSIS{ PHAKOMATOSIS } - VON RECKLINGHAUSEN’S DISEASE

Systemic features

• The neurofibromatoses are a group of hereditary disorders
• It primarily affects the cell growth of neural tissues.
• Inheritance is AD with irregular penetrance and variable expressivity.
• The mutation rate is high.

The main types are:

1. Neurofibromatosis 1 (peripheral form) which is the most common. Gene locus- 17q11,AD

2. Neurofibromatosis 2 (central form) mainly consisting of bilateral acoustic neuromas with few if any cutaneous findings. Gene- 22q12

Segmental : Both may show segmental involvement in which the features are confined to one or more body segments.

Neurofibromatosis type 1

Systemic features

1. Intracranial tumours - primarily meningiomas and gliomas. 
   
   
2. Neurofibromas 
• It may develop anywhere along the course of peripheral or autonomic nerves - but do not occur on purely motor nerves. 
• They may also involve internal organs. 
1. Discrete cutaneous neurofibromas are small, soft, violaceous nodules or larger pedunculated flabby lesions. 
2. Nodular plexiform neurofibromas feel like a ‘bag or worms’ when palpated. Involvement of the eyelid gives rise to the characteristic S-shaped deformity. 
3. Diffuse plexiform neurofibromas may infiltrate widely and deeply into surrounding structures. Associated overgrowth of soft tissue and thick redundant folds of skin may result in considerable disfigurement. 
   
   
3. Skeletal. Short stature, mild macrocephaly (enlarged head), facial hemiatrophy, absence of the greater wing of the sphenoid bone, scoliosis and thinning of long bone cortex. 
   
   
4. Skin 
• Café-au-lait spots are light-brown macules that are most commonly found on the trunk. They appear during the first year of life and increase in size and number throughout childhood; teenagers and adults invariably have more than six. 
• Axillary or inguinal freckles usually become obvious around the age of 10 years and are pathognomonic. 
  
  
5. Associations include malignancies, hypertension and mental handicap. 

NF 1 : Diagnostic criteria

Two or more of the following must be present:

• Six or more café-au-lait macules over 5 mm in greatest diameter in pre-pubertal children, and over 15 mm in greatest diameter in post-pubertal individuals.
• Two or more neurofibromas of any type, or one plexiform neurofibroma. 
• Axillary or inguinal freckling.
• Optic glioma.
• Two or more Lisch nodules (iris hamartomas).
• A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudoarthrosis.
• A first degree relative (parent, sibling, or offspring) with NF1 by the above criteria.

Ophthalmic features

1. Orbital involvement may be caused by one of the following:

(a) Optic nerve glioma develops in about 15% of patients.

• It may be unilateral or bilateral.
• typically presents between the ages of 4 and 8 years.
• with a gradual onset of unilateral proptosis and visual impairment.
• The optic disc may show either atrophy or oedema.
• In about 90% of patients, the tumour involves the anterior aspect of the optic canal and causes an enlargement of the optic foramen.
• tends to extend posteriorly to involve the chiasm and hypothalamus.
• Ultrasonography and CT show an enlargement of the optic nerve.
  
  
• Other orbital neural tumours such as (Orbital plexiform neuroma.)
• neurilemmoma,
• plexiform neurofibroma and
• meningioma.

(b) Spheno-orbital encephalocele

• It is caused by absence of the greater wing of the sphenoid bone.
  (Congenital defect in the sphenoid bone) 
• It characteristically causes a pulsating proptosis,( pulsatile congenital proptosis) 
• Not associated with a bruit or a thrill. 

2. Eyelid neurofibromas,

• which may be either nodular or plexiform,
• tend to develop early in life.
• When involving the upper lid, they frequently cause a mechanical ptosis.
• It is associated with a characteristic S-shaped deformity.

3. Iris lesions

(a) Lisch nodules

• Bilateral
• Melanocytic iris hamartomas (Lisch nodules)
• develop during the 2nd–3rd decades and are eventually present in 95% of cases. 
• universal after the age of 16 years.
• The nodules have a smooth outline and are dome shaped.

(b) Congenital ectropion uveae is uncommon and may be associated with glaucoma. 

(c) Mammillations are rare.

4. Prominent corneal nerves may occur.

5. Glaucoma is rare and

• when present, is usually unilateral and congenital. and is frequently associated with an ipsilateral lid neurofibroma.
  (About 50% of patients with glaucoma manifest ipsilateral neurofibroma of the upper eyelid and facial hemiatrophy.)

6. Fundus lesions

 
(a) Choroidal naevi, which may be multifocal and bilateral, are common. Patients with NF1 and naevi are at increased risk for the subsequent development of choroidal melanoma.

(b) Retinal astrocytomas, identical to those in tuberous sclerosis, are rare.

(c) Choroidal hamartomas are present in about 30% of cases. They appear as discrete flat or slightly elevated areas of hyperpigmentation, dark brown-black in colour.

Neurofibromatosis type 2

∙ Neurofibromatosis 2 (NF2) is less common than NF1.

∙ Inheritance is AD with the gene locus on 22q12.

 

Diagnostic criteria

1. Bilateral acoustic neuromas which usually present in the late teens or early 20s with hearing loss, tinnitus or imbalance.

Most acoustic neuromas are schwannomas arising from the vestibular nerve. In young patients tumour growth is invariably fast, whereas in older patients the lesion may be either slow- or rapid-growing. Recent advances in microsurgical techniques have significantly improved the results of surgery. The gamma knife (stereotactic radiotherapy) provides a therapeutic option.

2. A patient with a first-degree relative with NF2 who also has either a unilateral acoustic neuroma or two of the following: neurofibroma, meningioma, glioma, schwannoma or juvenile cataract.

Ophthalmic features

The following ocular lesions are often the first signs of the disease and may therefore assist in pre symptomatic diagnosis:

1. Cataract affects about two-thirds of patients.  - Post subcapsular cataract
The opacities develop prior to the age of 30 years and
It may be posterior subcapsular or capsular, cortical or mixed.

2. Fundus lesions consisting of combined hamartomas of the retinal pigment epithelium and retina, and
perifoveal epiretinal membranes are relatively common.

3. Ocular motor defects are present in about 10% of cases.

4. Less common findings include

optic nerve sheath meningioma,
optic nerve glioma,
unilateral Lisch nodules and
an abnormal electroretinogram.