Some zebras have spots

A young woman in her 20s asked to come see me in consultation. She had been told, "An endocrinologist won't do anything for you that we aren't already doing." It was not until recently that one of her providers finally complied with her request.

She had her first menses at age 9. After a few years, however, menses stopped. Further evaluation was not performed until age 18. It was subsequently discovered that she had a hypothalamic glioma, which was surgically resected. She had hyperprolactinemia and was on bromocriptine in addition to oral contraceptives. No one had made a diagnosis or offered further recommendations, other than refilling her medications.

I asked her: "Do you have any birth marks or freckles?"

She rolled up her sleeve: "Like this one?"

She pointed out a large café-au-lait spot to me. On physical examination, I found several other café-au-lait spots. I also noted extensive freckling, including in the axilla. There was no one else in her family with similar findings or history that she knew of. Her father, however, died suddenly in his early 40s from a heart attack. She was uncertain, but thought that it may have been from uncontrolled hypertension.

According to the NIH diagnostic criteria, an individual who has two or more of the following features has neurofibromatosis type 1 (NF1):

Six or more café au lait macules larger than 5 mm in individuals before puberty and larger than 15 mm in individuals after puberty.
Two or more neurofibromas of any type or one plexiform neurofibroma.
Freckling in the axillary or inguinal regions.
Optic glioma.
Two or more Lisch nodules (iris hamartomas).
Distinctive osseous lesions such as sphenoid dysplasia or tibial pseudarthrosis.
A first-degree relative with NF1 defined by the above criteria.

Based on these criteria, she has neurofibromatosis type 1 (NF1). I explained her diagnosis and what it means. I strongly encouraged any family members who think they might also be afflicted to come see me.

NF1 is inherited in an autosomal dominant manner. About 50% of cases are due to de novo mutations. Genetic testing is available, but most patients can be diagnosed by clinical features. Although there is no way to prove it, her father may have had NF1, too. It could have been the cause of his uncontrolled hypertension and early death. In addition to the dermatologic, neurologic and other classic features, NF1 can cause hypertension due to renal artery stenosis, coarctation of the aorta and sometimes pheochromocytoma.

Patients with NF1 should have annual physical exams, blood pressure monitoring and developmental assessment in childhood. Ophthalmologic evaluation should be conducted every year in young children, less often in adults. Those with neurologic, skeletal or cardiovascular abnormalities should be monitored as appropriate for those complications. Other studies or evaluation are advised only if indicated based on signs and symptoms.