A 20-Year-Old Woman With Nail Abnormalities and Vomiting

Sumaira Nabi, MBBS; Shahzad Ahmed, MBBS; Mazhar Badshah, MBBS


June 06, 2019


This patient was diagnosed with tuberous sclerosis (TS) with renal angiomyolipomas. Also referred to as "tuberous sclerosis complex," TS is an inherited (autosomal dominant) neurocutaneous disorder. It was first described in 1880 by Bourneville and is also known as "Bourneville disease." It is characterized by multisystem involvement, including the brain, skin, eyes, heart, lung, liver, and kidneys in different combinations with varying severity.[1] In the United States, 1 in 6000 newborns is affected; worldwide, 2 million people are estimated to have TS.[2]

TS is caused by mutations of the TSC1 gene on chromosome 9 and the TSC2 gene on chromosome 16, which encode for the proteins hamartin and tuberin, respectively.[3,4] These proteins are tumor suppressors and regulate cell division, growth, and differentiation.

TS is characterized by the development of various benign tumors in different organ systems of the body. The phenotypic expression varies greatly. Almost all patients have one or more of the characteristic skin lesions.[5] The typical dermatologic features include ash-leaf macules; these are elliptical, 0.5-2 cm in size, hypopigmented, and most commonly found on the trunk and lower extremities. These lesions may be present at birth. Angiofibromas, previously called "adenoma sebaceum," typically involve the malar aspects of the face, as is seen in the patient in this case (Figure 1).

Figure 1.

These erythematous lesions have an increased growth during puberty and are sometimes misdiagnosed as acne. Shagreen patches have an orange peel or leathery texture. These connective tissue hamartomas are often seen in children aged 2-6 years and are located over the lower trunk, as was seen in this case (Figure 2). Periungual and subungual fibromas develop later on and occur more commonly on the toenails (Figures 3 and 4).[6]

Figure 2.

Figure 3.

Figure 4.

Brain lesions typical of TS include cortical tubers; subependymal nodules; subependymal giant cell astrocytoma (SEGA); and dysplastic, dysmyelinated white-matter lesions. Subependymal nodules are areas of rounded hypertrophic tissue and are usually seen as discrete or confluent calcified spots on CT scans of the brain. They are distributed along the walls of the lateral ventricles. These nodules and cortical tubers are visualized in nearly 90% of patients on MRI of the brain; SEGAs are seen in 5%-20% of cases.[7,8] The severity of neurologic manifestations is proportional to the burden of radiologic disease. Symptoms include seizures, mental retardation, and behavioral dysfunction. Seizures are encountered in almost 90% of cases and are typically difficult to treat.[9]

Renal involvement is common. Angiomyolipoma is the most common renal manifestation and is seen in 50%-80% cases, including the patient in this case (Figures 5 and 6).[9]

Figure 5.

Figure 6.

Angiomyolipomas may arise from the renal cortex or medulla. They are benign and are usually bilateral and multiple. An increase in the size of angiomyolipomas leads to pain and can cause hematuria and disturbance of renal function. Other lesions include benign cysts, lymphangiomas, and renal cell carcinoma.[9] Eye involvement may be retinal (astrocytic hamartomas) and nonretinal (coloboma, eyelid angiofibroma, nonparalytic strabismus, refractive errors, papilledema).[10]

Multiple skeletal manifestations are recognized, including sclerotic lesions; scoliosis; and bone cysts in metatarsals, metacarpals, and phalanges.[11] The most characteristic cardiovascular feature is rhabdomyoma,[12] which is found on echocardiography in approximately 50% of patients with TS. Rhabdomyomas can lead to valvular dysfunction, outflow obstruction, cardiomyopathy, and cardiac arrhythmias. Coarctation of the aorta and aortic aneurysm have also been documented. Pulmonary manifestations of TS include a cystic lung disease known as lymphangioleiomyomatosis (LAM). LAM presents with dyspnea and pneumothorax. Rarely, liver leiomyomas or adenomas may be present.


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