SDHB – Cowden Disease

Limited evidence supports an association between heterozygous SDHB variants and Cowden disease in PTEN mutation–negative individuals. In a cohort of 375 PTEN‐negative CS/CS‐like patients, three unrelated probands harbored germline SDHB missense variants (c.8C>G (p.Ala3Gly)) (PMID:18678321). No familial segregation data are available, and a single case report described no pathogenic SDHB mutations in a patient with Cowden‐like features (PMID:23804288).

Functional assays demonstrated elevated plasma succinate in the sole SDHB‐mutant individual (1/1) compared with controls, indicating mitochondrial complex II impairment concordant with CS‐like biochemical alterations (PMID:22261759). However, small proband numbers and lack of segregation limit clinical validity.

Key Take‐home: SDHB variants may contribute to a Cowden‐like phenotype in PTEN-negative patients, but evidence is currently insufficient for routine genetic testing.

References

• American journal of human genetics • 2008 • Germline mutations and variants in the succinate dehydrogenase genes in Cowden and Cowden-like syndromes. PMID:18678321
• Head & neck • 2014 • Unusual case of Cowden-like syndrome, neck paraganglioma, and pituitary adenoma. PMID:23804288
• Genetics in medicine • 2012 • Elevated plasma succinate in PTEN, SDHB, and SDHD mutation-positive individuals. PMID:22261759

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