Tuberous Sclerosis Complex

Clinical History

A 29 year old female presented to the Emergency Department with complaint of chest pain for the past 5 days. This pain initiated on the left side and is now bilateral. It is exacerbated with movement and breathing. There is no fever, cough, or chills. No treatment was received prior to arrival.

Findings

Diagnosis
Tuberous Sclerosis Complex

Discussion
Tuberous Sclerosis Complex is a rare, inherited neurocutaneous disorder that is known to cause benign hamartomas in a range of organ systems, including the brain, eyes, skin, lung, liver, kidneys, and heart. The expression of this disease varies substantially. GENETICS: This disease is an autosomal dominant disorder however only one-third of cases are familial. The other two-third of cases are caused by either mosaicism – where some cells have the mutation and others do not or spontaneous mutations. A mutation in TSC1 and TSC2 genes which are located on chromosome 9 and chromosome 16, respectively have been identified to be the major cause of this disease. The proteins that are coded by these 2 genes are known to interact and form a complex that negatively regulate the cell cycle.1

CLINICAL FEATURES: Presentation of seizures, mental retardation, and facial angiofibromas is called the classic triad of TSC also known as Vogt’s triad. Less than 50 percent of patients, however, presents with this triad. In the past, this made it difficult for physicians to diagnose the majority of these patients. Therefore in 1998, a range of presentation of Tuberous Sclerosis Complex were grouped into major and minor diagnostic criterias. Presentation of two major criterias or one major and two minor criterias, encompasses a diagnosis for TSC.2

Major criterias are Facial angiofibromas, shagreen patch, hypomelanotic macules, periungual fibromas, Lymphangioleiomyomatosis, subependymal nodules, renal angiomyolipoma, cortical tubers, subependymal giant cell astrocytoma, subependymal nodules, multiple retinal nodular hamartomas, and cardiac rhabdomyoma. Minor criterias are confetti skin lesions, multiple renal cyst, gingival fibromas, pits in the dental enamel, cerebral white matter radial migration lines, nonrenal hamartomas, bone cyst, and retinal achromic patch. Exception is that isolated finding of Lymphangioleiomyomatosis (LAM) and renal angiomyolipoma in a patient, does not place them at a higher risk of having an affected child and therefore these patients are not considered to have TSC.

Management of TSC is dependent on the presentation of the patient. Of most concern would be the control of major causes of death in this patient population. Subependymal giant cell tumors and status epilepticus are the most common causes of death.3 Surgical resection of brain tumors is indicated when there is an hydrocephalus or increased intracranial pressure, interval increase in tumor size, or new focal neurological deficit that is attributable to the tumor. Additive and less frequent causes of death are renal complications such as renal cell carcinoma, hemorrhage into angiomyolipoma, and renal failure.

Submitted by Ellis Enabosi, MS-III (School of Medicine) and Richard Desruisseau, M.D., Department of Radiology (Chief, Musculoskeletal Section) at Meharry Medical College, Nashville, TN.
 
References:
1. Tee AR, Fingar DC, Manning BD, et al. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A 2002; 99:13571.
2. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 1998; 13:624.
3. Shepherd CW, Gomez MR, Lie JT, Crowson CS. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc 1991; 66:792.