DISCUSSION
The earliest clinical study of neurofibromatosis (NF), among Nigerian
patients, was reported by Ademiluyi and Ijaduola, in 198821. The paper described the clinical features of 14
children with NF, seen over a 6-year period. Ademiluyi and Ijaduola,
made the important observation that in blacks, the typical CALMs consist
more of hyperpigmented macules (café), with very few hypopigmented
patches (laît) preferably referred to as Café sans laît spots in black
patients 21. Their observation is corroborated in this
current study, where it was observed that, hypopigmented macules are
very rare, in black African patients, in comparison to the
hyperpigmented spots, some of which are also difficult to identify,
against the backdrop of their dark-skinned complexion (Figure 2b). This
lends credence to Freidman’s earlier assertion that the intensity of
pigmentation of CALMs are dependent on the degree of pigmentation of the
background skin 6. Therefore, a preponderance of dark/
hyperpigmented macules (café sans laît macules, CSLM) is to be expected
in black African patients. The distribution of CALMs (or CSLMs) is
widespread over the body, although they are reported to spare the scalp,
eyebrow areas palms of the hands, and soles of the feet6. However, in this study, we observed hyperpigmented
CALMs on the palms of one patient simulating “freckling” (Figure 5d)
and multiple hyperpigmented macules on the scalp in another patient
(Figure 2d).
Interestingly, despite the fact, that CALMs (or preferably CSLMs) are
the most common feature of NF among our patients, they are the least
concerning to them and are often overlooked as “birth marks”, and the
presence or proliferation of CALMs (CSLMs) does not prompt patients to
seek consultation 1,7. Moreover, despite the presence
of prominent cutaneous, and less commonly, subcutaneous neurofibromas,
which are more striking and not easily ignored, many patients still fail
to seek consultation, even for these swellings; especially if there is
also a parent or sibling with similar lesions. While cutaneous
neurofibromas tend to be painless and slow-growing, subcutaneous nodules
may become painful 6.
Plexiform neurofibromas on the other hand, do seem to prompt medical
consultation, probably because of their progressive increase in size,
propensity for disfigurement and their tendency to cause pressure
symptoms or, in the case of lid lesions, impairment of vision22. Plexiform neurofibromas can be nodular or diffuse6. Consequently, it is not surprising that progressive
increase, in size of a lid lesion, was the commonest reason for
consultation in our study.
We recorded a much higher prevalence of plexiform neurofibromas (84.8%)
in our present study in comparison to another study on NF1, carried out
in Ilorin, Nigeria 24, which reported only 8.2%
plexiform neurofibromas. This may be attributed to the worrisome
cosmetic effects of facial and orbito-ocular masses or, to the tendency
for plexiform neurofibromas of the lid to cause ptosis, or compress the
globe, resulting in visual impairment; thereby prompting early
presentation.
Ophthalmic manifestations of NF are somewhat under-reported in African
patients and in African literature. For instance, Odebode et al.
reported ophthalmological examination in only 5 out of 98 patients24. Nevertheless, Lisch nodules have also been
reported in individual case reports of African patients with NF136,37. The Lisch nodules in our study were raised,
light yellow, nodules on the iris, which demonstrated increasing
prevalence and preponderance with age, similar to descriptions in
literature 6,13,38,39. Our youngest patients with
Lisch nodules were aged 5 years, which is relatively early. Lisch
nodules characteristically occur after the first decade of life6 although Lisch nodules have been described in a
child as young as 2 years of age 13 . Prevalence of
Lisch nodules correlates with age and is a highly specific sign for
diagnosis, even in asymptomatic relatives, but has no other clinical
significance 6,8,13. It is a valuable practice; to
examine accompanying relatives in all suspected cases of
neurofibromatosis as the presence of Lisch nodules alone is enough to
establish a positive family history 4,7,8,38.
Other anterior segment manifestations of NF are much less common than
Lisch nodules and include, glaucoma, ectropion uvea, cataract,
conjunctival neurofibroma, prominent corneal nerves and optic pathway
glioma. While we documented glaucoma in one case, which was ipsilateral
to a large plexiform lid neurofibroma, there was no case with ectropion
uvea. We documented full cataract in two cases, however, it is possible
that these were incidental. Posterior subcapsular cataract has been
documented in association with NF type 2, and is an important diagnostic
criterion in the presence of a unilateral acoustic neuroma40,41. We also had a case of conjunctival
neurofibroma, which is rare 40. Conjunctival
neurofibroma may be associated with significant keratinization of the
overlying epithelium due to exposure and irritation. We observed
prominent corneal nerves in two cases, corneal nerves become prominent
as they hypertrophy in the corneal stroma 13. They are
visible only within 1-2 mm of clear cornea beyond the limbus and can
easily be missed if not specifically sought.
Optic pathway gliomas and intracranial tumours, though rare, occur with
a higher frequency in patients with NF, than the general population1,42. The prevalence of optic pathway gliomas in this
study was 8.8%. However, compared with other reports from Nigeria, this
is the only study which reports the presence of these tumours10,20-26,28-30,36,43-51. We also identified a rare
primary brain glioma in one child with sporadic NF127. The child had not previously been diagnosed as a
case of NF and had presented as a painless, red eye, with loss of
vision. Suspicion of an underlying neuro-cutaneous disorder, was raised
by the large hyperpigmented forehead patch (Figure 2d), which led to a
search for the other diagnostic signs. The child had CALMs (Figure 2c),
Lisch nodules and a plexiform neurofibroma of the ankle, which had been
excised twice before, but never sent for histological examination. It
was therefore important, for the ophthalmologist, to recognize the
significance of papilloedema in his contralateral eye and insist on
neuroimaging, which identified the intraventricular tumour. Despite the
large size, the child had no history of headaches, though he was having
difficulties with his performance at school. This emphasizes the
importance of clinical observation and detailed examination in the
African setting, because clinical history is often sparse. Another case
that reiterates the above fact is the 17 year old presenting with poor
vision and bilateral optic atrophy. His mother had all the signs of NF1,
but had never been diagnosed. He had received several spectacle
prescriptions and was referred for low vision aids, without a diagnosis.
It was the presence of Lisch nodules on slit lamp examination of the
patient that prompted a search for other diagnostic signs, which
revealed cutaneous nodules, Lisch nodules (Figure 6b) and CSLMs in the
mother, sufficient to make a diagnosis of NF1 (in the mother) and a
positive family history of NF, for the patient. Notably, some of the
CSLMs were barely perceptible in the 17 year old (Figure 2b, arrow).
However, it was in the context of this background NF that the optic
atrophy (Figure 6c and d) took on new significance; prompting an
insistence on neuroimaging and the eventual diagnosis of
optic-hypothalamic pathway glioma (Figure 6a and b).