The clinical profile of tuberous sclerosis complex (TSC) in the United Kingdom: A retrospective cohort study in the Clinical Practice Research Datalink (CPRD).

BACKGROUND: Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder characterised by the development of benign growths and diverse clinical manifestations, varying in severity, age at onset and with high clinical burden. AIMS: This longitudinal study aims to describe the broad spectrum of clinical manifestation profiles in a large, representative cohort of TSC patients in the UK in order to better understand disease complexity. METHODS: TSC patients in the Clinical Practice Research Datalink (CPRD) and linked Hospital Episodes Statistics (CPRD-HES) were retrospectively identified between 1987 and 2013. Available history was extracted for each patient and clinical diagnosis, procedure and medication records reviewed. A random selection of patients from the CPRD-HES was used as a Comparator cohort. RESULTS: Three hundred and thirty-four TSC patients with a mean (SD) age of 30.3 (18.6) years were identified (53% female). TSC was diagnosed at mean age 3.2 (4.2) years. Epilepsy and psychiatric manifestations were reported frequently in paediatric (77% and 55%, respectively) and adult patients (66% and 68%, respectively). The prevalence of manifestations in the TSC cohort was markedly higher versus the Comparator cohort. The majority of paediatric (46%) and adult TSC patients (62%) developed clinical manifestations affecting at least three organ systems and forty-nine distinctive organ system manifestation profiles were identified. CONCLUSIONS: TSC patients present with multiple and complex clinical manifestations and profiles that necessitate the co-ordinated action of a multidisciplinary team in order to improve the quality and efficiency of care.

Angiomyolipomata: challenges, solutions, and future prospects based on over 100 cases treated.

OBJECTIVE: To examine the presentation, management and outcomes of patients with renal angiomyolipoma (AML) over a period of 10 years, at St George's Hospital, London, UK. PATIENTS AND METHODS: We assessed retrospectively 102 patients (median follow-up 4 years) at our centre; 70 had tuberous sclerosis complex (TSC; median tumour size 3.5 cm) and the other 32 were sporadic (median tumour size 1.2 cm). Data were gathered from several sources, including radiology and clinical genetics databases. The 77 patients with stable disease were followed up with surveillance imaging, and 25 received interventions, some more than one. Indications for intervention included spontaneous life-threatening haemorrhage, large AML (10-20 cm), pain and visceral compressive symptoms. RESULTS: Selective arterial embolization (SAE) was performed in 19 patients; 10 received operative management and four had a radiofrequency ablation (RFA). SAE was effective in controlling haemorrhage from AMLs in the acute setting (six) but some patients required further intervention (four) and there was a significant complication rate. The reduction in tumour volume was only modest (28%). No complications occurred after surgery (median follow-up 5.5 years) or RFA (median follow-up 9 months). One patient was entered into a trial and treated with sirolimus (rapamycin). CONCLUSIONS: The management of AML is both complex and challenging, especially in those with TSC, where tumours are usually larger and multiple. Although SAE was effective at controlling haemorrhage in the acute setting it was deemed to be of limited value in the longer term management of these tumours. Thus novel techniques such as focused ablation and pharmacological therapies including the use of anti-angiogenic molecules and mTOR inhibitors, which might prove to be safer and equally effective, should be further explored.