MedGen

Mitochondrial complex II deficiency nuclear type 3 (MC2DN3) is an autosomal recessive multisystemic metabolic disorder with a highly variable phenotype. Some patients may have an encephalomyopathic picture with episodic developmental regression, loss of motor skills, hypotonia, ataxia, dystonia, and seizures or myoclonus. Other patients present in infancy with hypertrophic cardiomyopathy, which may be fatal. Laboratory studies show increased serum lactate and mitochondrial complex II deficiency in muscle and fibroblasts (summary by Jackson et al., 2014 and Alston et al., 2015). For a discussion of genetic heterogeneity of MC2DN, see MC2DN1 (252011). [from OMIM]

Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis) and pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas cause catecholamine excess; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base and neck (referred to as head and neck PGL [HNPGL]) and sometimes in the upper mediastinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically lead to catecholamine excess. Symptoms of PGL/PCC result from either mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for developing metastatic disease is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas. [from GeneReviews]

A familial syndrome characterized by gastrointestinal stromal tumors and paragangliomas, often at multiple sites. It is a very rare syndrome presenting at a young age. The gastric stromal sarcomas are multifocal and the paragangliomas are multicentric. The clinical spectrum of this syndrome varies widely, depending on the localization and the size of the tumors. The vast majority of cases are due to germline mutations of the succinate dehydrogenase (SDH) subunit genes SDHB, SDHC and SDHD. Predisposition to developing these tumors is inherited in an autosomal dominant manner with incomplete penetrance. [from SNOMEDCT_US]