Recognition of tuberous sclerosis in adult women: delayed presentation with life-threatening consequences

Abstract

Background: Tuberous sclerosis complex (TSC) is associated with tumor development in the brain, retina, kidney, skin, heart, and lung. Seizures, intellectual disability, and characteristic skin lesions commonly manifest in early childhood, but some findings, notably renal angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM), emerge later, placing adults with undiagnosed TSC at increased risk for morbidity and mortality.

Objective: To describe the clinical presentation and severity of TSC in adult women.

Design: Retrospective cohort study.

Setting: National Institutes of Health Clinical Center, Bethesda, Maryland, 1995 to 2010.

Patients: 79 women aged 18 years or older who were enrolled in an observational cohort study of TSC to evaluate disease manifestations.

Measurements: History, physical examination, pulmonary function testing, chest radiography, abdominal computed tomography, high-resolution chest computed tomography, and brain magnetic resonance imaging were used to evaluate patients.

Results: Among the 45 patients who received a diagnosis of TSC in adulthood, 21 presented with symptoms due to LAM, 19 with renal angiomyolipomas, and 10 with seizures. Of the 45 patients, 30 met clinical criteria for TSC in childhood that remained undiagnosed for a median of 21.5 years and 15 were older than 18 years before meeting the clinical criteria for TSC. Patients diagnosed in adulthood and those diagnosed in childhood had similar occurrences of pneumothorax, shortness of breath, hemoptysis, nephrectomy, and death.

Limitation: No men were included in the study, and selection was biased toward patients having pulmonary LAM.

Conclusion: Women who received a TSC diagnosis in adulthood had minimal morbidity during childhood but were still at risk for life-threatening pulmonary and renal manifestations.

Primary funding source: Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute.

Figure 1. Major and minor diagnostic features of tuberous sclerosis complex in adult women

A. Multiple facial angiofibromas, often scattered symmetrically across the nose and cheeks and concentrated in the nasal groove. B. Forehead plaque, pink to red-brown fibrous plaques that can be located anywhere on the face or scalp, with adjacent white scar from skin biopsy. C. Ungual fibromas, emerging from around or under the nail and more common on the toes than fingers. D. Hypomelanotic macules, with a polygonal or ash-leaf shape, under fluorescent lighting (left) and accentuated with a Wood lamp (right). E. Shagreen patch, a connective tissue nevus usually situated on the lower back. F. Dental pitting, pinpoint to crater-like defects in the enamel. G. Computed tomography scan of multiple renal angiomyolipomas in the left kidney in a patient after right nephrectomy. H. Magnetic resonance image of multiple cortical tubers, including a large cortical tuber in the left parietal lobe (arrow). I. Magnetic resonance image of multiple cortical tubers, calcified subependymal nodules (arrows).

Figure 2. Clinical characteristics of tuberous sclerosis complex with early or late penetrance

The estimated frequencies of findings (0% to 100%) over time are represented by the filled areas. Patients with tuberous sclerosis complex diagnosed in childhood (dark green) typically experience onset of multiple manifestations of the disease in the first 5 years. Patients with adult penetrance (light green) do not meet clinical criteria for diagnosis in childhood and have lower frequencies of brain and skin involvement in adulthood. The substantial variations in disease severity between patients or the potential for changing disease severity over time for 1 patient are not indicated. Patients at risk for a delay in diagnosis (not shown) have childhood penetrance but minimal illness in childhood.