Download Case Report-Neurofibromatosis Type I

Case Report-Neurofibromatosis Type I
Yu-Ho Cheng, OD; Susan P. Schuettenberg, OD, FAAO
Abstract:
Neurofibromatosis type I (NF-1) is the most common phakomatosis (1 in 4000). It is
characterized by pigmented skin lesions (café-au-lait spots), and multiple peripheral nerve
tumors (neurofibromas). This case report documents the systemic and ocular signs, diagnosis,
and management of a 25 year old white male patient diagnosed with NF-1.
I. Case History
a. 25 year old white male
b. Complains of occasional mild dry eyes OU
c. Medical history positive for Neurofibromatosis type I, obesity, and mental
retardation
d. Ocular history positive for optic nerve glioma, and dry eye syndrome.
Optic nerve glioma diagnosed at age two and irradiated in 1985
e. Medication includes Loprox gel, and Systane eye drops
f. Family History: (+) Lisch nodules-father (no other manifestations of NF).
Patient has 5 unaffected siblings, 2 have been diagnosed with cone
dystrophy
II. Pertinent findings
a. BCVA: 20/70+ OD, 20/80 OS. PERRL –APD. Full EOM. Unreliable
confrontation VF results due to unsteady fixation OU. Biomicroscopy
examination showed multiple bilateral iris Lisch nodules . Dilated fundus
examination revealed overall nerve pallor OU, and 1 de-pigmented
CHRPE lesion in the peripheral retina, OD. Color vision with Ishihara
plates OD: 11/12, OS 10/12.
b. Physical exam: (+) multiple neurofibromas, left arm. (+) abdominal caféau-lait spots.
III. Differential diagnosis of NF type I
a. Systemic- when cutaneous hamartomas present:
i. Leading: NF type II
ii. Others: Watson syndrome, LEOPARD syndrome, Tuberous
sclerosis, Von Hippel-Lindau disease, Proteus syndrome, and
Sipple syndrome
b. Ocular
i. Iris:
1. Leading: Lisch nodules
2. Other: Busacca nodules, Koeppe nodules
ii. Optic nerve:
1. Optic nerve glioma
2. Others: retinoblastoma, hamartomas of the optic disc of RP,
ischemic optic neuropathy, pseudotumor cerebri, optic
neuritis
IV. Diagnosis and discussion-NF type I
a. NF is one of the Phakomatoses - a group of hereditary disorders that are
characterized by the presence of hamartomas on a variety of body tissues.
b. Two common forms of NF
i. Type I (Von Recklinghausen disease): involving peripheral
nervous system
ii. Type II: involving central nervous system
c. Inheritance pattern of NF type I: autosomal dominant with the gene locus
on 17q11. Presents with irregular penetrance, variable expressivity, and
high mutation rate.
d. Prevalence of NF type I: 1/4000. No race or sex predilection.
e. Pathophysiology: mutation of NF-1 gene on chromosome 17q11loss of
gene product (neurofibromin) that serves as tumor suppressor in the
nervous system increased risk of developing benign and malignant
tumors
f. Systemic signs:
i. Intracranial tumors: meningiomas and gliomas
ii. Neurofibromas
iii. Skeletal anomaly
iv. Skin lesions i.e. café-au-lait spots, axillary/inguinal freckles
g. Ocular features:
i. Orbital: optic nerve glioma, neurolemmoma, meningioma, sphenoorbital encephalocele
ii. Eyelid neurofibromas
iii. Iris lesions: Lisch nodules, congenital ectropion uveae
iv. Prominent corneal nerves
v. Congenital glaucoma
vi. Fundus lesion: choroidal nevus, retinal astrocytomas
h. Diagnostic criteria: Two or more of the following signs must be present
i. 6 or more café-au-lait spots
ii. 2 or more neurofibromas
iii. Axillary or inguinal freckling
iv. Optic nerve glioma
v. Two or more Lisch nodules
vi. A distinctive osseous lesion such as sphenoid dysplasia or thinning
of long bone cortex, with or without pseudoarthrosis
vii. A first degree relative with NF-1 by the above criteria
i. Diagnostic tests
i. Systemic
1. Prenatal testing-chorionic villus sampling
2. Audiogram
3. Brainstem auditory-evoked response
ii. Ocular
1. MRI of orbit with contrast
2. CT of orbit
3. VEP
j. Other Association
i. Cognitive problems and behavioral difficulties with NF-1
individuals
1. IQ in the lower average range
2. Specific learning problems observed in 30-60% children
with NFI: Reading/writing difficulties, Visual spatial
problems, working memory impairment, attention deficit
ii. Behavioral problems
1. Sleep disturbance, impaired socialization, low self-esteem,
and poor interpretation of social cues
iii. Malignant peripheral nerve sheath tumors (MPNST)
1. 8-13% lifetime risk of MPNST in NF-1
2. Most susceptible from 20-35 years of age
3. High rate of metastasis and hard to detect
iv. Cardiovascular problems: congenital heart disease, hypertension
V. Treatment, and management
a. General guideline: age specific monitoring of disease and patient
education most important
i. Children with uncomplicated disease need to be assessed at least
once a year
ii. Adults with mild disease or asymptomatic: minimal annual blood
pressure measurement and awareness of unusual symptoms of
MPNST
iii. Adults with severe disease require lifelong monitoring at a NF-1
specialty clinic
iv. All NF-1 patient should be educated on symptoms of MPNST
b. Skin lesions: Café-au-lait spots and freckles usually don’t cause
complication, but are indicative of possible diagnosis
c. Neurofibromas:
i. can cause transient stinging and pruritis
1. Lubricate with emollients, avoid excessive heat
2. Can be removed by surgical means/ carbon dioxide laser
d. Optic nerve gliomas
i. Often asymptomatic
ii. Risk of symptomatic optic gliomas is greatest for children <7 years
old and can result in reduced VA, abnormal color vision, visual
field loss, papillary abnormalities, pale optic disc, proptosis, and
hypothalamic dysfunction
iii. Children with NF-1 under age 7 should have annual dilated eye
exam including VA, fundus evaluation
iv. Color vision and VF should be done when child is mature enough
v. Treatments:
1. Vincristine and cisplatinum
2. Surgical removal
3. Radiotherapy
4. Rapamycin-on going research as future management for
optic gliomas
e. Genetic Counseling
i. An individual with NF-1 has 50% risk of passing it on to offspring
ii. Important to examine individuals with cutaneous involvement or
Lisch nodules
1. Segmental/mosaic form of NF-1: can increase risk of
having child with NF-1
VI. Conclusion
a. Lisch nodule can be one of the earliest signs of NF-1 before any systemic
signs appear. Primary eye care providers can be the first line of health
care professional to diagnose NF-1
b. It is essential for children to have regular dilated eye exam to pick-up
potential sight-threatening orbital tumors such as optic nerve glioma in
NF-1
c. Management of patients with NF-1 is a life-long process that involves age
specific monitoring and patient education