tuberous sclerosis

What’s the Cause of This Girl’s Cutaneous Lesions?

William Shin, MD

An 11-year-old girl presented to our clinic with history of patches of light-colored skin on her abdomen (Figure 1). The lesions had been present since birth. She also had red bumps on her upper chest (Figure 2) and on her cheeks and chin (Figure 3).


The girl was healthy, although she complained that she sometimes has difficulty with reading comprehension. There were no other neurologic or systemic symptoms and no relevant family history of seizures or learning disabilities. Her siblings were not examined but were said to be in good health. A computed tomography (CT) scan of the head was performed and showed numerous bilateral subependymal calcifications.



What could explain these symptoms?

A. Tuberous sclerosis

B. Neurofibromatosis type 1

C. Cowden disease

D. Multiple endocrine neoplasia type 1

(Answer and discussion on next page)

Answer: A, tuberous sclerosis

Tuberous sclerosis, also called tuberous sclerosis complex (TSC), is a rare, multisystem, genetic disease that causes benign tumors to grow in the brain and other organs, such as the kidneys, heart, eyes, lungs, and skin. Tuberous sclerosis refers to the pathologic finding of thick, firm, pale gyri in the brains of patients on postmortem examination. It usually affects the central nervous system and is associated with skin abnormalities.

Most cases of tuberous sclerosis occur sporadically as a result of new, spontaneous mutations of the TSC1 or TSC2 genes, which code for the proteins hamartin and tuaberin, respectively. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation. However, tuberous sclerosis is an autosomal dominant disorder in some cases.

Tuberous sclerosis occurs in all races and ethnic groups and equally in both sexes. Many people with tuberous sclerosis show evidence of it in the first year of life. However, clinical features can be subtle initially and can take years to develop. As a result, it can go unrecognized or misdiagnosed for years.

Tuberous sclerosis can affect numerous systems of the body, causing a variety of signs and symptoms. The natural course varies from individual to individual, with symptoms ranging from very mild to quite severe. Neurologic symptoms can include seizures, cognitive impairment, mental retardation, and behavioral problems. Dermatologic symptoms can include hypomelanotic macules on the skin with either an ash leaf or a confetti-like appearance, red patches on the face (hamartomas) containing many blood vessels, and raised patches of skin with an orange-peel texture (shagreen patches), often on the back.

The diagnosis of tuberous sclerosis is based on clinical criteria. In many cases, the first clue is the presence of seizures or delayed development. In other cases, the first sign may be white patches on the skin or the identification of cardiac rhabdomyomas. In addition to a careful clinical physical examination, the diagnostic workup can include CT or magnetic resonance imaging of the brain, which may show cortical or subependymal tubers, and ultrasonography of the heart, liver, and kidneys, which may show tumors in those organs. In infants, tuberous sclerosis may be suspected if the child has cardiac rhabdomyomas or experiences seizures (infantile spasms) at birth.

Tuberous sclerosis has no cure. Antiepileptic medications can be used to control seizures. Vigabatrin is particularly useful and has been approved by the U.S. Food and Drug Administration (FDA) for infantile spasms, such as those associated with tuberous sclerosis, in infants and children 1 month to 2 years of age. The FDA also has approved the immunosuppressant everolimus for pediatric and adult patients with tuberous sclerosis and subependymal giant cell astrocytoma, and adults with renal angiomyolipoma related to tuberous sclerosis. Dermabrasion and laser therapy have been used to treat skin lesions.

All individuals with tuberous sclerosis are at risk for life-threatening conditions from tumors of vital organs, but with appropriate care, most have a normal life expectancy.

William Shin, MD, is a pediatrician at Aju Medical Center in Queens, New York.

Kirk Barber, MD, FRCPC—Series Editor, is a consultant dermatologist at Alberta Children’s Hospital and clinical associate professor of medicine and community health sciences at the University of Calgary in Alberta.