G103(P) An Interesting Case of Two Siblings With SDHB Mutations. (4th June 2013) - Mitting, RB
Abstract : Phaeochromocytoma presenting in childhood is rare. 1 It commonly presents with the effects of catecholamine excess, the most consistent of which is hypertension. 2 3 Patients with phaeochromocytoma presenting in childhood often have a predisposing genetic mutation. 1 2 Carriers of succinate dehydrogenase complex subunit B (SDHB) mutations are at risk of developing paraganglionoma/phaeochromocytoma, and these tumours have a high rate of malignancy. 3 SDHB mutations are also associated with gastro-intestinal stromal tumours. 4 They are inherited in an autosomal dominant fashion. 5 We present a case of a 15 year old girl (AB) and her 4 year old sister (MB), who both presented in 2011. AB was diagnosed with an extra-adrenal phaeochromocytoma, (paraganglionoma), and MB with intestinal pseudo-obstruction. Both patients have been found to have SDHB mutations. AB presented with seizures and decreased level of consciousness, requiring intubation and ventilation. It was initially difficult to obtain non-invasive blood pressure (BP) measurement, and once an arterial line was inserted, BP was 255/177. This settled without intervention at the time. Once transferred back to DGH, BP remained 120–70 systolic, so an ultrasound scan was performed, which revealed a mass adjacent to the aortic bifurcation, and urinary catecholamines measured, which revealed raised noradrenaline, and urinary VMA. The mass was removed, and histology confirmed extra-adrenal phaeochromocytoma. MB presented with bilious vomiting and abdominal distension, so was transferred to a tertiary hospital under the care of the surgical team. She required 3 weeks of TPN and was given a diagnosis of intestinal pseudo-obstruction. Following these episodes, both patients received genetic counselling, and were found to have SDHB mutations, which they inherited from their father. This case highlights the importance of accurate blood pressure measurement in paediatrics, especially in Accident and Emergency. Hypertension in children is rare, 5 and therefore when it is discovered, it should be investigated thoroughly as a cause is likely to be found. We are reminded of the need for genetic counselling for children with phaeochromocytoma/paraganglionoma and their siblings, as there is a high risk of genetic mutations and, once genetic mutations are identified, there is a risk of synchronous and metanchronous cancers. References: Waguespack SG, Rich T, Grubbs E, et al. A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 2010;95:2023–37. Hammond PJ, Murphy D, Carachi R, et al. Childhood phaeochromocytoma and paraganglioma: 100% incidence of genetic mutations and 100% survival. J Pediatr Surg 2010;45:383–6. Van Hulsteijn LT, Dekkers OM, Hes FJ, et al. Risk of malignant paraganglioma in SDHB-mutation and SDHD-mutation carriers: a systematic review and meta-analysis. J Med Genet 2012;49:768–76. Pasini B, McWhinney SR, Bei T, et al. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germlines mutations of the genes coding for succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 2008;16: 79–88. Armstrong R, Shridar M, Greenhalgh KL, et al. Phaeochromocytoma in children. Archives of Disease in Childhood 2008;93:899–904.