Does hidradenitis suppurativa (HS) have a strong genetic or inheritance pattern, particularly in a pregnant patient?

Genetic and Inheritance Pattern of Hidradenitis Suppurativa

Yes, HS demonstrates a moderate genetic component with approximately 30-42% of patients reporting a positive family history, though the inheritance pattern is complex and not consistently strong across all cases. 1, 2

Familial Inheritance Pattern

Autosomal dominant inheritance has been documented in familial HS cases, though with variable penetrance that makes the pattern less predictable than classic Mendelian disorders. 3

• A landmark study examining 14 families found 10 affected and 9 possibly affected individuals among 37 first-degree relatives, falling short of the expected 50% mark for autosomal dominant inheritance 3
• The reduced penetrance may be explained by hormonal influences on gene expression, variable gene penetrance, and the need for additional environmental triggers 3
• Seven new cases developed in previously studied families over a 15-year follow-up period, supporting the autosomal dominant model 3

Monogenic vs. Polygenic Forms

Monogenic mutations account for less than 7% of HS cases, with the majority representing polygenic, multifactorial disease. 4

Monogenic Forms (Rare)

• Mutations in γ-secretase complex genes (NCSTN, PSENEN, PSEN1) are the most commonly identified monogenic causes 1, 4
• Patients with γ-secretase mutations typically present with more severe disease and earlier age of onset 4
• These mutations affect the Notch signaling pathway and can result in follicular occlusion 1

Polygenic Forms (Common)

• Most HS cases result from multiple genetic variants affecting innate and adaptive immunity, skin microbiome, inflammasome function, epidermal homeostasis, and keratinization pathways 2, 5
• Recent studies define HS as a polygenic, multifactorial, autoinflammatory disease rather than a simple inherited condition 2

Clinical Implications for Genetic Counseling

Family history screening is recommended but genetic testing is not currently indicated for diagnosis or management. 1

• While 30-40% of patients report family history, there is no current role for genetic or biomarker testing in clinical diagnosis 1, 6
• The disease can be categorized as familial HS, sporadic HS, syndromic HS, or "HS plus" associated with other syndromes 2
• Early-onset disease (before age 20) is more strongly associated with positive family history 2

Important Caveats

• Twin studies demonstrate high heritability, reinforcing genetic factors in pathogenesis, but environmental triggers (smoking, obesity, hormonal factors) remain critical 2
• The female predominance and post-pubertal onset suggest hormonal modulation of genetic susceptibility 1
• Insufficient disease definition and variable penetrance can lead to underestimation of familial cases 3

Pregnancy-Specific Considerations

Pregnant patients with HS should be counseled that while genetic factors contribute to disease susceptibility, the inheritance pattern is not strongly predictive, and many cases occur sporadically without family history. 1

• Clinical improvement is often observed during pregnancy, suggesting hormonal influences on disease expression 1
• The complex genetic architecture means offspring risk cannot be precisely quantified, though first-degree relatives have elevated risk compared to the general population 3