Guidelines for Management of Children with Neurofibromatosis I

GUIDELINES FOR MANAGEMENT OF CHILDREN WITH NEUROFIBROMATOSIS I

INTRODUCTION

Neurofibromatosis I (Von Recklinghausen disease) is a common inherited autosomal dominant disorder with an incidence of 1 in 2500-3000 births. About half the cases are the first in their family and mosaic NF1 may occur as a result of mutation in the NF1 gene. The disease principally affects the skin and peripheral nervous system. The disease is progressive so that distinctive features may be present at birth but the development of complications, which may involve any of the body systems, can be delayed for decades. The expression and severity of NF1 varies even within families.

DIAGNOSIS

2 or more of the following are necessary for diagnosis:

·  6 or more cafe au lait macules (> 5mm in prepubertal and >15mm in postpubertal children)

·  Axillary or inguinal freckling

·  2 or more neurofibromas of any type or one plexiform neurofibroma

·  Optic glioma

·  2 or more Lisch nodules (iris hamartomas)

·  Distinctive osseous lesion ( e.g. sphenoid dysplasia, bowing of long bones) +/- pseudoarthrosis

·  First degree relative with NF1 by above criteria

MANAGEMENT

At Diagnosis:

·  Detailed family history

·  Examination of the skin

·  Examination of long bones and spine

·  Detailed developmental assessment

·  Complete neurological examination

·  Ophthalmology assessment

·  Genetic counselling and referral

·  Laboratory test in asymptomatic patients is unlikely to be of value

ANNUAL ASSESSMENTS

Yearly surveillance recommended for early detection of treatable conditions and complications.

·  Growth assessment: Plot height,weight and head circumference

·  Pubertal development: assess for signs of delayed or precocious puberty

·  Ophthalmology assessment: fundoscopy, visual fields and acuity

·  Blood pressure

·  Evaluation of the spine (for scoliosis/underlying plexiform neuroma)

·  Evaluation of the skin

·  Development and progress in school

·  Multi-disciplinary review –only if indicated following disability

Referrals and notifications

·  General practitioner

·  Ophthalmologist

·  Paediatric neurologist(William-please comment if and when necessary)

·  Education

·  Geneticist

·  Occupational therapy and physiotherapy(if necessary)

·  Dermatologist(Jane please comment if and when necessary)

SPECIFIC PROBLEMS AND MANAGEMENT

A. SKIN

Cutaneous and subcutaneous neurofibromas develop in adolescence. They may cause cosmetic problems, itching unresponsive to antihistamines or transient stinging. They rarely undergo malignant change.

·  Surgical removal for symptomatic lesions

·  Carbon dioxide laser may be helpful for small lesions

·  Risk of hypertrophic scarring and recurrence after removal

Plexiform neurofibromas may be associated bony and soft tissue hypertrophy. There is a 10% lifetime risk of malignant change, most common in the 2nd and 3rd decades. Individuals should seek urgent expert advice if the following develop;

·  Persistent pain for > 1 month

·  New neurological deficit

·  Change in texture from soft to hard or rapid increase in size

B. VISION

Problems include Glaucoma, Sphenoid wing dysplasia resulting in proptosis, exophthalmos or enophthalmos and Plexiform neurofibroma involving eyelid orbit.

Optic pathway glioma occur predominantly in children under 7 years.

·  Annual visual assessment

·  Refer to ophthalmologist for specific problems

·  Brain MRI screening for optic pathway glioma is not indicated as treatment is not required in the absence of progressive symptoms

·  Seek expert advice for management of OPG- this should be led by the opthalmologist

C. NEUROLOGICAL

Epilepsy; particularly complex partial seizures may occur.

Tumours include cerebral and optic gliomas, ependymoma, and medulloblastoma.

Neurofibromatosis neuropathy; a mild symmetrical distal tingling numbness or weakness. Malformations, including aqueductal stenosis. Cerebrovascular disease

Pressure effect on nerves and spinal cord from plexiform neurofibromas

·  Neurological examination should be undertaken during annual assessment

·  Refer to paediatric neurologist if any unexplained neurological signs or symptoms

D. CARDIOVASCULAR

Problems include congenital heart disease and hypertension

·  Annual blood pressure check

·  Careful cardiovascular examination.

·  If hypertensive recheck 3 times over a one month period to verify findings

·  Check upper and lower limb blood pressure to look for aortic coarctation

·  Consider renal artery stenosis

·  Check 24 hour urinary catecholamines if phaeochromocytoma suspected

·  Seek advice/refer to cardiologist unexplained findings

E. ORHTOPAEDIC

Bowing of long bones +/- pseudoarthrosis presents in infancy and will not develop de novo once fully mobile.

Scoliosis may be idiopathic or dystrophic

·  Spine should be checked yearly

·  Refer scoliosis for orthopaedic assessment

F. COGNITIVE & BEHAVIOURAL

Problems may occur as cognitive delay

References

1) Clinical Guidelines for the management of individuals with neurofibromatosis Type 1. The Neurofibromatosis Association