Tuberous sclerosis: a case report

Introduction

Tuberous sclerosis complex (TSC) is an unusual autosomal dominant neurocutaneous syndrome characterized by the development of benign tumors affecting different body systems affecting the brain, skin, retina, and viscera. It is characterized by cutaneous changes, neurologic conditions, and the formation of hamartomas in multiple organs leading to morbidity and mortality. The management of these patients is often multidisciplinary involving specialists from various fields. The affected genes are TSC¹ and TSC², encoding hamartin and tuberin respectively.

The Neural involvement in TS  is characterized by the presence of glial cell tumors arising in the cerebral hemispheres and retina. TS is clinically characterized by the triad of epilepsy (EPI), intellectual disability (LOI), and adenoma sebaceum (A), therefore, encompassing these features Sherlock coined the term EPILOIA.²

Here, we present a case report of a 6 year male child with characteristic clinical, radiological, features of tuberous sclerosis complex.

Case Report

A 6 year old child was brought with the complaints of asymptomatic reddish brown small hard bumps occupying mid-face since 2 years. Multiple white patches of irregular shape had been noted by the parents on the trunk and thigh. There were 2 redorange colored wrinkled patches on back. There was history of seizures since one year, for which the child was under treatment of a neurologist. He was born on full term for parents of a consanguineous marriage. His younger brother was normal There was no history indicative of the disease either in maternal or paternal family members.  

On examination, the face showed presence of multiple reddish–brown papules of 2-4mm size, over the nose, and cheeks. They were bilateral and and were symmetrical in distribution (Fig.1a).

There was a plaque of 3-4 cm size in lumbosacral region. It had uneven surface, resembling an orange peel (the shagreen patch) (Fig. 1b). Hypomelanotic, ivory-white macule (s) of 5 to 10 mm size was noted on the trunk and posterior aspect of left arm. The macules were 8 in number and were well defined with irregular margins [Fig. 1c]. The mucous membrane of the oral cavity and nails were normal.

The CT of the brain revealed subependymal calcifications over lateral ventricals, and ill-defined hypodense lesions in the parietal lobe.

Discussion

Tuberous sclerosis complex is an autosomal dominant disorder that affects the patient and the family members in various ways.

It is a disorder of cellular differentiation and proliferation that can affect the brain, skin, kidneys, heart and other organs. Many of the clinical features result from hamartomas, but true neoplasms also occur, particularly in the kidney and brain. Abnormal neuronal migration plays a major additional role in neurological dysfunction. An estimated incidence is one case per 6,000 live births. If individuals who are mildly affected were considered then the rate might be much higher. Approximately 60-70% of TSC cases are thought to be result of new mutations. About 30% of normal parents had TSC.The cutaneous findings are usually the first clue that patient has TSC but other features may lead to diagnosis. Patients with TSC have several typical dermatologic findings. Onset before the age of five years with cutaneous changes or with epilepsy is usual, although the disease may remain latent until adolescence or adult life.Facial angiofibromas are found in 75 percent of affected patients. These lesions appear after 5 years of age and may be mistaken for acne. But these show wide variation in age of onset and severity.³

The ash-leaf spot is the earliest skin lesion in patients with TSC. This hypomelanotic macule is most easily visualised with a Wood’s light.

About 90 to 96 percent of patients may develop ash leaf spots by the age of 4 yr. By themselves; these macules are not diagnostic of tuberous sclerosis because they are also relatively common in the general population.The shagreen patch, a thickened orange peel textured area of connective tissue hamartoma is most often found on the mid to lower back. This lesion develops in 21 percent of patients with tuberous sclerosis. Shagreen patches may develop between 2and 6 years of age. Ungual fibromas are more prominent in adolescents and adults and they are fairly specific to tuberous sclerosis. Patients can also have sublingual or perilingual fibromas. In our case all  cutaneous lesions were seen, except nail and mucosal.

The predominant neurological manifestations of TSC are mental retardation, seizures and behavioural abnormalities.But milder forms have little or no neurological impairment.The classical triad of TSC consisting of skin lesions, mental retardation and epilepsy is said to be present in about one third of patients.The seizures usually start occurring before2 years of age. Intelligence is normal in one fourth patients with seizures but nearly all mentally retarded patients have seizures. In our case patient had history of seizures and average IQ.

The present case had facial angio-fibroma, shagreen patch, and hypo-melanotic ash leaf macule, few of its salient cutaneous manifestations,h/o seizure and radiological changes , adequate to consider the diagnosis of TSC, conforming to the major features.⁵

Conclusion

Although tuberous sclerosis complex is a well-known genetic disorder, its reporting is sporadic. Slowly evolving angio-fibroma affecting the mid face, shagreen patch, and hypo-melanotic, confetti-like lesions should arouse suspicion.⁵

The dermatologic manifestations of tuberous sclerosis are helpful in diagnosing this disorder. Unfortunately no specific prenatal laboratory test is available. Genetic counselling should be offered to families with affected members, even though accurate counselling remains difficult because of the variabilityof gene expression. All the patients diagnosed to have TSC should be evaluated for this by 2-D Echo, ECG, USG abdomen,cranial CT, and CT of the chest. There is no cure for TSC, but the symptoms can be treated and/or managed. Surgery,including dermabrasion and laser treatment may be useful for treatment of skin lesions. Seizures are treated with antiepileptic drugs and systemic complications are treated symptomatically. As TSC is a lifelong condition, regular surveillance to look for symptoms and early treatment are associated with better health and quality of life outcomes for people with TSC.⁶