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tuberous_sclerosis_complex

Tuberous sclerosis complex

Tuberous sclerosis complex (TSC), AKA Bourneville’s disease, is a neurocutaneous disorder characterized by hamartomas of many organs including the skin, brain, eyes and kidneys. In the brain, the hamartomas may manifest as cortical tubers, glial nodules located subependymally or in deep white matter, or giant cell astrocytomas. Associated findings include pachygyria or microgyria.

Tuberous sclerosis complex (TSC) was initially described approximately 150 years ago by von Recklinghausen in 1862 1).

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disease usually diagnosed in childhood.

Subependymal giant cell astrocytomas (SEGA) are benign brain lesions occurring in up to 20% of patients with TSC.

This rare multi-system genetic disease causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease.

The name, composed of the Latin tuber (swelling) and the Greek skleros (hard), refers to the pathological finding of thick, firm and pale gyri, called “tubers,” in the brains of patients postmortem. These tubers were first described by Désiré-Magloire Bourneville in 1880; the cortical manifestations may sometimes still be known by the eponym Bourneville's disease.

Epidemiology

Studies estimate a frequency of 1/6000 to 1/10,000 live births and a population prevalence of around 1 in 20,000 2) 3).

Etiology

TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation. 4) 5)

Diagnosis

The most common findings are benign tumors in the skin, brain, kidneys, lung, and heart that lead to organ dysfunction as the normal parenchyma is replaced by a variety of cell types 6).

Disease manifestations in different organ systems can vary widely between even closely related individuals and the protean nature of the condition can make clinical diagnosis challenging. TSC was underdiagnosed until the 1980s when individuals with less severe manifestations of the disease began to be recognized. Before the 1980s, incidence rates for TSC were quoted at between 1/100,000 and 1/200,000 7) 8).

Case series

Brain MRIs of 110 TSC patients (mean age 11.5 years; age range 0.5-38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests.

Eight of 110 (7.2%) TSC patients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSC patient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSC patients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample.

Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects 9).

Case reports

A novel technique is presented for the application of MRgLITT in a 6-month-old infant for the treatment of epilepsy associated with tuberous sclerosis complex (TSC) .

To Hooten et al. from the Tuberous Sclerosis Complex Clinic, Duke University, Durham, North Carolina; and University of Florida, Gainesville, knowledge this is the youngest patient treated with laser ablation. They used a frameless navigation technique with a miniframe tripod system and intraoperative reference points. This technique expands the application of MRgLITT to younger patients, which may lead to safer surgical interventions and improved outcomes for these children 10).

1)
von Recklinghausen F. Die Lymphelfasse und ihre Beziehung zum Bindegewebe. [German]. Berlin: A. Hirschwald; 1862.
2)
O’Callaghan F, Shiell A, Osborne J, Martyn C. Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet. 1998;352:318–319.
3)
Sampson J, Scahill S, Stephenson J, Mann L, Connor J. Genetic aspects of tuberous sclerosis in the west of Scotland. J Med Genet. 1989;26:28–31.
4)
European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993;75:1305–1315.
5)
van Slegtenhorst M, deHoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277:805–808.
6)
Northrup H, Koenig M, Au K. Tuberous sclerosis complex. GeneReviews. 2011 http://www.genetests.org.
7)
Stevenson A, Fischer O. Frequency of epiloia in Northern Ireland. Br J Prev Soc Med. 1956;10:134–135.
8)
Nevin N, Pearse W. Diagnostic and genetical aspects of tuberous sclerosis. J Med Genet. 1968;5:273–280
9)
Manara R, Brotto D, Bugin S, Pelizza MF, Sartori S, Nosadini M, Azzolini S, Iaconetta G, Parazzini C, Murgia A, Peron A, Canevini P, Labriola F, Vignoli A, Toldo I. Rhinencephalon changes in tuberous sclerosis complex. Neuroradiology. 2018 Jun 17. doi: 10.1007/s00234-018-2045-x. [Epub ahead of print] PubMed PMID: 29909560.
10)
Hooten KG, Werner K, Mikati MA, Muh CR. MRI-guided laser interstitial thermal therapy in an infant with tuberous sclerosis: technical case report. J Neurosurg Pediatr. 2018 Sep 28:1-6. doi: 10.3171/2018.6.PEDS1828. [Epub ahead of print] PubMed PMID: 30265228.
tuberous_sclerosis_complex.txt · Last modified: 2019/02/09 08:18 by administrador