The Not-So-Beautiful “Bow Tie”—Tuberous Sclerosis

Author: Susong Children's Hospital Affiliated to Shandong University

Reviewer: Zhang Hongwei, deputy chief physician, Children's Hospital Affiliated to Shandong University

Tuberous sclerosis, also known as "bow-tie disease", is a rare and complex disease, and is included in the first batch of rare disease catalogs in my country. About 1 million people in the world suffer from this disease, and May 15th of each year is International Tuberous Sclerosis Awareness Day. Due to the variety of manifestations of this disease, many patients may not be diagnosed for years or even decades. Therefore, everyone needs to understand it, seek medical treatment early, diagnose early, and treat early. Let us learn about what tuberous sclerosis is and how it is treated?

What is tuberous sclerosis complex?

Tuberous sclerosis complex is an autosomal dominant genetic disease that affects multiple systems, including skin, brain, eyes, oral cavity, heart, lung, kidney, liver, bones and other organs, where benign hamartomas or nodules may occur. Typical manifestations are epileptic seizures, intellectual impairment, and facial angiofibromas (sebaceous adenomas). The incidence rate is 1/6000. About 2/3 of the patients are secondary to mutations in the TSC1 or TSC2 tumor suppressor genes.

How to detect tuberous sclerosis complex early?

Tuberous sclerosis is essentially a benign hamartoma that affects multiple organs, including the skin, brain, eyes, mouth, heart, lungs, kidneys, liver, and bones. When multiple organs are affected, corresponding symptoms will appear, but the symptoms of each patient vary in severity.

First of all, skin damage is usually the first manifestation that is easily discovered. Skin damage has unique characteristics, including white spots that are lighter than normal skin, also called "depigmented spots". About 90% of patients have this change. There are also reddish-brown or skin-colored angiofibromas on the face, local gravel-like thickening of the skin, forehead plaques, fleshy nodules under or around the nails, and shark skin-like plaques.

Secondly, a common manifestation is epileptic seizures. 90% to 95% of patients will experience neurological changes, and the most common manifestation of the nervous system is epileptic seizures. Epilepsy caused by tuberous sclerosis complex is usually refractory epilepsy, and two or more anti-epileptic drugs may be needed to control the seizures or it may be difficult to control the seizures.

Figure 1 Copyright image, unauthorized reproduction

Finally, what is often discovered is intellectual disability. The patient's language and intellectual development are significantly slower than those of children of the same age. Some patients cannot even speak and cannot complete simple tasks such as eating and dressing themselves. Therefore, many parents take their children to the hospital for treatment because of this symptom.

Various "tumors" may appear in other systems, including abnormal white matter, cortical tubers, subependymal giant cell tumors, cardiac rhabdomyomas, intracranial nodules, fundus retinal hamartomas, pulmonary lymphangiomyoma, angiomyolipoma, gingival fibroma, local bone sclerosis, etc. When corresponding compression symptoms appear, the patient will go to the hospital for treatment.

Figure 2 Copyright image not authorized for reproduction

What tests are needed if tuberous sclerosis is suspected?

Since tuberous sclerosis is a hereditary disease, essentially a benign hamartoma involving multiple organs, genetic testing is necessary to help guide diagnosis and treatment and determine prognosis. It is also necessary to complete relevant examinations such as cranial magnetic resonance imaging, electroencephalogram, intelligence and mental behavior assessment, cardiac ultrasound and electrocardiogram, abdominal imaging examination, high-resolution CT of the lungs, fundus examination, skin examination, etc. In addition, it is necessary to regularly check various indicators and monitor the changes in the condition of each affected system. If corresponding symptoms occur, symptomatic treatment is required.

What is the treatment and prognosis of tuberous sclerosis complex?

In fact, the most important issue for everyone is how to treat and the effect after treatment. Since the tumor will not disappear by itself after it is formed, and there is currently no effective way to eliminate the tumor, it is necessary to stop it in time before it appears on a large scale, reduce the appearance of the tumor, reduce the pressure of the tumor, and minimize the impact of the disease on the patient's life and life span, and reduce the disability rate. Therefore, for this disease, early detection, early diagnosis, and early treatment are very important.

Combined with the pathogenesis of tuberous sclerosis, there are currently drugs targeting the growth of tuberous sclerosis tumors, mTOR pathway inhibitors, including sirolimus, everolimus, etc., which can inhibit the growth of tumors, but for tumors that have already grown, only symptomatic treatment is currently available. ① Anti-epileptic treatment (conventional anti-epileptic drugs, ketogenic diet, surgical operation, etc.): There are many types of anti-epileptic drugs, and their mechanisms of action are also different. It is necessary to comprehensively select appropriate anti-epileptic drugs based on the patient's seizure type, and perform epilepsy surgical intervention when necessary; ② Skin changes: For various changes in the skin, laser, liquid nitrogen freezing and electrocautery can be considered; ③ Tumors of other systems: If the tumors of each system are too large, compression symptoms appear or affect life, symptomatic treatment of surgical removal of the tumor can be performed; ④ When patients have developmental delays, they need psychological treatment and cognitive function rehabilitation. Since tuberous sclerosis complex is an autosomal dominant genetic disease, corresponding genetic testing and family counseling can be performed, and effective intervention strategies can reduce the birth of affected children. For high-risk families with fertility needs, genetic testing is needed, especially for patients of childbearing age or those considering having children, fertility counseling should be provided, and they should be given prenatal examinations and diagnosis to achieve the goal of eugenics.