Teaching Case

A 7-month-old male patient with known clinical history of a intracardiac mass on fetal ultrasound was admitted to the paediatric department with three episodes of non-febrile seizures.

CT images in Fig 1a and b show hyperdense, well-defined, intra-axial nodules on the borders of the lateral ventricles suggestive of subependymal nodules. Fig 1c reveals a slightly hyperdense, round, intra-axial lesion located in the frontal right lobe with peripheral hypoattenuation.
MRI in Fig 2a demonstrates isointense subependymal nodules in T1WI and mild hypointensity on T2WI (yellow arrows). Fig 2b depicts subcortical hypointensity in the frontal right lobe consistent with a subcortical tuber. No restricted diffusion is present (Figure 2c).
A round, echogenic mass is noted on the right ventricle wall on echocardiography Fig 3a and b suspicious for rhabdomyoma.
Hypomelanotic lesions on the patients lower back (Fig 4a) as well as on patients mother (Fig 4b) are present.

Tuberous sclerosis is an autosomal dominant disease [1]. It is the second most common phakomatosis after neurofibromatosis. Mutations occur in genes encoding for hamartin and tuberine, proteins that regulate cell growth, thus the predisposition tumour formation (hamartomas) in different organs [2].
Birth incidence is 1 in 6, 000-10, 000, prevalence is 1:20, 000 [1].
Clinical findings (Vogt triad) include: seizures, skin lesions and mental retardation.
Imaging is needed to rule out tumours, risk of organ failure and to consider appropriate treatment [1].

The most common lesions encountered are:
- Skin lesions: Characterised by angiofibromas, fibrous plaques and/or hypomelanotic lesions.
- Central nervous system: Lesions such as tubers and subependymal nodules (found in ~90% of patients), subependymal giant cell astrocytomas (SEGA) and white matter migration lines.
Cortical or subcortical tubers represent disorganised neurons. In CT examinations they appear as triangular-shaped hyperdense lesions commonly located in frontal lobes. On MRI they appear hypointense on T1WI and hyperintense on T2WI as well as on FLAIR sequences. Three types of tubers (A, B and C) have been proposed, each different findings on MRI sequences [3, 4]. Subependymal nodules border the ventricles and appear as hyperdense nodular lesions on CT, they tend to calcify as patient ages. On MRI and CT they may show variable enhancement upon contrast administration. They appear hyperintense on T1WI and hyperintense/isointense on T2WI and FLAIR [3].
- Heart lesions include striated-muscle tumours known as rhabdomyomas, which are found in 50-80% of cases. Most are asymptomatic, few cause arrhythmia or cardiac failure. On echochardiography they appear as single or multiple, nodular hyperechoic, well-defined lesions that usually tend to regress during childhood [5].
- Other lesions include the kidneys, where angiomyolipomas may be found as multiple and bilateral. Pulmonary manifestations are almost exclusively found in women and include lymphangioleiomyomatosis. Rarely the liver and spleen can be affected by angiomyolipomas or hamartomas.

Clinical diagnostic criteria have been proposed since 1988 by Roach et al. These criteria may classify tuberous sclerosis in definite, probable or possible [6].
Strict follow-up is necessary. Annually dermatologic and ophthalmologic examination as well as brain and abdomen MRI is needed, the latter may be performed every 1-3 years. Echocardiography should be performed annually until rhabdomyomas regress. For women at risk for Lymphangioleiomyomatosis, Lung CT is mandatory every 5-10 years [3, 7, 8].
Treatment options vary among the affection of different organs. Anti-epileptic drugs are the standard management but surgery on epileptogenic focus lesions may be performed [8, 9].