Café-au-lait spots and Neurofibromatosis

Dr. Greene's Answer

Both Joseph (John) Merrick, the Elephant Man, and Quasimodo, the Hunchback of Notre Dame, are dramatic examples that have shaped our perceptions of neurofibromatosis. NF, also known as von Recklinghausen disease, is one of humankind’s most common neurological genetic disorders, indeed it is one of the most common genetic disorders of any kind.

“Treat me as an equal!” cried Merrick, whose appearance caused him to be ridiculed and rejected by 19th-century England. This courageous, intelligent, sensitive poet could find employment only as a sideshow freak.

Merrick’s mother was once watching a parade when, in the crush of spectators, she was pushed under an Elephant’s feet, “which frightened her very much,” wrote Merrick. “This occurring during a time of pregnancy was the cause of my deformity.”

Some doctors didn’t agree.

Merrick was brought before the Pathological Society of London by Sir Frederick Treves. A diagnosis of NF was finally made in 1909. So firm was this diagnosis that NF came to be called “Elephant Man’s disease.” The photograph of Merrick’s notorious disfigurement became the indelible image of NF in the minds of those familiar with it.

Not until the 1980’s did we learn that Merrick didn’t have NF but an unrelated condition called proteus syndrome (British Medical Journal, 1986; 293:683–685). I didn’t know this in 1982 when I read Merrick’s poignant three-page autobiography — after my surgeon told me he thought I might have NF.

Neurofibromatosis is a genetic disorder of the nervous system that causes benign tumors to form on the nerves anywhere in the body at any time. At least eight varieties of NF exist and can range from very mild to quite severe (Clinical Pediatric Dermatology, WB Saunders,1993), but fortunately none are as disfiguring as the tragic case of the Elephant Man.

Café-au-lait spots are a classic feature of this disease. These flat birthmarks with distinct edges are a bit darker than the surrounding skin. In light-skinned individuals, they are the color of coffee with lots of cream. In those with darker skin, they can be the color of a rich, full-bodied, black coffee. The spots can increase in size, number, and darkness throughout childhood.

Having one to three café-au-lait spots is quite common, present in as many as one in five healthy children. Each spot of significant size after the first three, though, is increasingly uncommon and increasingly likely to be associated with NF or with one of the other neurocutaneous syndromes, including neurofibromatosis type 2, segmental neurofibromatosis, tuberous sclerosis, McCune Albright syndrome, Fanconi anemia, Bloom syndrome and ataxia telangiectasia (CMAJ, Aug 2002; 167:3.).

Neurofibromatosis is diagnosed not with a test but by the presence of certain physical findings. People can receive a firm diagnosis of NF Type 1 if they have any two of the following symptoms (Textbook of Pediatrics, WB Saunders, 2000):

• At least six café-au-lait spots more than 5 mm in the greatest diameter (before puberty) or at least six café-au-lait spots of more than 15 mm (after puberty).
• Underarm or groin freckling (called axillary or inguinal freckling).
• Two or more Lisch nodules (small nodules in the iris of the eye).
• Two or more neurofibromas (rubbery lumps under the skin, often slightly purplish over the lump –these usually don’t show up before puberty) or one plexiform neurofriboma (thickened nerve trunks, often on the face – these are usually apparent at birth).
• A bone lesion consistent with NF, such as thinning of the long bones.
• Optic gliomas (small benign tumors of the optic nerve–most still have normal or near-normal vision).
• A close relative with NF (parent, sibling, or child).

Many of these findings do not show up in early childhood. Thus, any child with six or more café-au-lait spots that are more than 5 mm in diameter should be monitored and treated as having NF. This means a baseline examination by an ophthalmologist and audiologist (including vision and hearing tests) and a visit with a geneticist. It also means considering a baseline EEG and head CT or MRI, as well as a skeletal survey radiograph.

Each parent should have these same tests performed on him or her; siblings may be evaluated as well. NF is often so mild that a parent isn’t diagnosed until café-au-lait spots are found on his or her child. Often, a child’s course of disease follows that of his or her parents. Those with a presumptive diagnosis of NF need annual vision and hearing testing, as well as an annual neurologic and skeletal exam (in addition to a regular physical). Children with NF1 should have their growth followed on a special growth chart. They should be monitored for high blood pressure. Over the course of a lifetime, patients with NF1 need to be closely followed because of the higher risk of several rare types of cancers.

Very recent research shows that children with NF can have a higher frequency of social problems, attention problems, anxiety or depression, aggressive behavior, and a lower frequency of involvement in sports and other activities. They may have developmental delays. These problems are often mild enough to be missed unless looked for. Early screening and treatment for speech, motor, and cognitive problems and an increased effort to prevent and treat psychological problems can make a huge difference in the lives of these children (Journal of Pediatrics, 1999; 134:767–772).

Although my condition turned out not to be NF, that period of uncertainty has left me feeling very close to my patients who have it. Joseph Merrick closed his autobiography with a portion of the poem that he passed out at his circus sideshow:

If I could reach from pole to pole
Or grasp the ocean with a span,
I would be measured by the soul;
The mind’s the standard of the man.
As it turns out, looks do matter.
Still

But progress in the treatment of disfiguring conditions is dramatic and accelerating every year. And progress in appreciating people for who they are is also being made, albeit at a slower pace.