Case history
Case history #1
A male infant is found to have multiple café au lait spots at his routine 6-month pediatric follow-up visit. The physician queries NF1 and refers the patient to a dermatologist, who concurs with the tentative diagnosis and refers the infant to the nearest university-based NF specialty clinic. There, a general physical exam is otherwise unrevealing and an ophthalmologic exam is normal. As is standard for this particular NF clinic, a screening cranial MRI is performed, revealing an optic pathway glioma involving the proximal right optic nerve and optic chiasm, as well as multiple hyperintense T2-weighted signals in the periventricular white matter, globus pallidus, and cerebellum. Given an otherwise negative family history and the lack of NF1 findings on physical exam of both parents, the family is counseled that a new NF1 mutation is likely. The optic pathway glioma will be followed by ophthalmologic exams and neuroimaging.
Case history #2
A 26-year-old woman presents with multiple sessile fleshy skin lesions. She has been aware of multiple café au lait spots since early childhood, although she ignored them as they were deemed to be birthmarks. The truncal skin lumps that led to her presentation began to appear (or become prominent) during the early second trimester of her recent pregnancy, at the end of which she delivered a female infant with multiple light brown birthmarks. Physical exam of the woman shows café au lait spots, bilateral axillary freckling, and multiple cutaneous neurofibromas over the trunk and proximal limbs. She has no neurologic abnormalities. A slit-lamp ophthalmologic exam reveals multiple iris Lisch nodules bilaterally. The diagnosis of NF1 is substantiated on clinical grounds. Genetic counseling clarifies the 50% recurrence risk of NF1, and respecting the patient's wish to have additional children free of NF1, a blood sample is obtained for a molecular diagnosis in anticipation of using the data for prenatal diagnosis, or preimplantation diagnosis and selective implantation of NF1-free conceptuses.
Other presentations
On the one hand, a patient may present with ≥1 defining lesions of NF1 (i.e., café au lait spots, neurofibromas, iris Lisch nodules) confined to a limited part of the body, with the ultimate explanation being somatic (postzygotic) mosaicism. As the gonads may be involved in the mosaicism, such a diagnosis may entail a significant risk for full-blown NF1 among offspring. On the other hand, at least one allelic form of NF1 has been shown to lack the typical cutaneous neurofibromas definitive of NF1, and patients with NF1 and whole-gene-deletion are likely to have more profound cognitive problems and an early childhood onset of cutaneous and subcutaneous neurofibromas.[4]
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