Pathogenic variants (disease-causing) in the SDHD gene can predispose individuals to tumors such as paragangliomas (head and neck tumor), but less often causes pheochromocytomas (adrenal gland tumor), and gastrointestinal stromal tumors (GIST – a rare gastric or small bowel cancer). Management of SDHD–related tumor risk includes regular surveillance tailored to guidelines for hereditary paraganglioma–pheochromocytoma syndromes, typically involving periodic biochemical testing, whole-body or targeted MRI, and clinical evaluation to detect tumors early. SDHD variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in SDHD exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family. However, a unique feature of the SDHD gene is called a ‘parent-of-origin effect’, meaning that increased tumor risk is seen almost exclusively when the pathogenic variant is inherited from the father, not the mother.
In addition, when an individual inherits pathogenic variants in both copies of the SDHD gene, it can cause a rare childhood-onset condition called mitochondrial complex II deficiency, which presents in infancy or childhood. This condition may result in severe neurological symptoms such as progressive loss of mental and physical abilities. Mitochondrial complex II deficiency exhibits autosomal recessive inheritance. This means that both parents must have a single pathogenic variant in the SDHD gene to have a 25% chance to have a child with the condition.
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Written December 2025
