Diagnosis of Tuberous Sclerosis Complex in Adulthood based on Late Presenting Cutaneous Manifestations

Case Report

J Fam Med. 2019; 6(4): 1174.

Diagnosis of Tuberous Sclerosis Complex in Adulthood based on Late Presenting Cutaneous Manifestations

Shalabi D, Sethi M, Lee H, Cha J and Nikbakht N*

Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA, USA

*Corresponding author: Nikbakht, N Department of Dermatology and Cutaneous Biology, 233 S. 10th Street, Rm 410, Philadelphia PA 19107, USA

Received: February 27, 2019; Accepted: April 25, 2019; Published: May 02, 2019


Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome characterized by the classical triad of intellectual disability, seizures, and skin findings. Cutaneous findings of hypopigmented macules and facial angiofibromas are usually the initial presenting symptoms in early childhood. However, a minority of patients do not develop such features early in life; instead they may present with alternative skin findings later in life causing a delay in diagnosis. Herein, we present the case of a 58-year old female with a history of seizures and renal disease who developed a Shagreen patch and ungual fibromas later in life. She was diagnosed with TSC in our dermatology clinic based on the presence of ungual fibromas. We report this case to highlight the necessity of recognizing late onset skin features of TSC, particularly in patients with seizures, to prevent delays in tumor screening and management.

Keywords: Tuberous sclerosis complex; Periungual fibromas; Shagreen patches; Collagenoma


TSC: Tuberous Sclerosis Complex


Tuberous sclerosis complex (TSC) is an inherited neurocutaneous syndrome characterized by the development of multi-organ hamartomas, usually of the brain, skin, kidneys, and eyes [1]. Estimated birth incidence of TSC is 1 in 6000 to 1 in 10,000 live births with a population prevalence of 1 in 20,000 [2,3]. The syndrome is inherited in an autosomal dominant pattern or presents as new spontaneous mutations in TSC1 and TSC2, encoding tumor suppressive genes hamartin and tuberin, respectively [1]. Dysfunctional hamartin and tuberin lead to constitutive activation of mammalian target of rapamycin (mTOR), promoting cell growth that result in the hamartomas of TSC.

Diagnosis of TSC relies on identifying key clinical features. The “classic triad” includes the presence of cutaneous angiofibromas, intellectual disability, and early onset seizures [4]. Angiofibromas, also known as fibrous papules of the face or adenoma sebaceum, present as multiple dome-shaped papules distributed symmetrically on the cheeks, nose, and chin. Although the full triad occurs in less than a third of the patients, nearly 100% have characteristic skin findings, which include, in addition to facial angiofibromas, hypopigmented macules, Shagreen patches, and ungual fibromas.

The 2012 International Tuberous Sclerosis Complex Consensus Group listed 11 major and 6 minor clinical features; either two major or one major and two minor criteria are sufficient for a definitive diagnosis [5]. Major cutaneous features include Shagreen patches (a type of connective tissue hamartoma or collagenoma presenting as a pink, yellow plaque with an orange peel like texture), =3 facial angiofibromas, =3 hypopigmented macules at least 5-mm in diameter, and =2 ungual fibromas, also known as Koenen tumors (skin colored nodules appearing on the proximal nail folds). More severe cases may present with multi-organ complications including pulmonary lymphangioleiomyomatosis, renal disease, cardiac rhabdomyomas, and subependymal giant cell astrocytomas of the brain [6].

Although TSC most commonly manifests and is diagnosed in infancy or childhood, cases have been reported of adult diagnoses [7,8]. We report a 58-year old female who initially presented with asymptomatic dermatologic findings and was subsequently diagnosed with TSC.

Case Presentation

A 58-year-old Caucasian female presented to our dermatology clinic for a nonspecific complaint. Incidentally, visible growths were noted along her nail folds, which led to a more thorough skin exam. Physical examination revealed discrete, smooth, skin-colored to pink firm papules along nail folds of multiple fingers (Figure 1) and toes (Figure 2); irregular, skin-colored, rubbery plaques on lower back (Figure 3), and stippled hypopigmented macules on the bilateral lower extremities. Skin findings on fingers and toes were previously diagnosed as warts. Upon further questioning, the patient endorsed a history of seizures of unknown etiology since infancy despite a detailed neurologic workup. She had been following with a nephrologist for chronic kidney disease in setting of known multiple bilateral renal cysts. Family history was positive for seizures, renal disease and similar nail fold findings in her daughter.