Intersex Traits Without a Named Genetic Condition

How XX or XY people can develop or function along the “opposite” sex-typical pathway

Scope & key idea

Most public explanations tie intersex strictly to known genetic diagnoses. In reality, some XX or XY individuals develop intersex traits—and may even function predominantly along the other sex‑typical pattern—without ever receiving a named genetic condition. Reasons include non-genetic hormonal environments in utero, loss of fetal gonadal function, and the fact that modern testing still leaves many cases undiagnosed. (PubMed Central)

How this can happen without a classic genetic label

1) Maternal androgen excess during pregnancy (non-genetic fetal cause)

Certain maternal conditions transiently raise androgens during pregnancy and can masculinize an XX fetus (e.g., atypical genital appearance at birth, later “male-typical” hair growth patterns), even when fetal genetics are ordinary XX. Classic examples include luteoma of pregnancy (an androgen‑producing ovarian growth that appears only during pregnancy) and ovarian/adrenal androgen–secreting tumors. (PubMed Central, BioMed Central)

• Luteoma of pregnancy has repeatedly been reported to virilize mothers and their XX newborn daughters; androgen levels fall after delivery because the lesion regresses. (PubMed, PubMed Central)

  
  

• Medication‑related androgen exposure (historically, danazol) has also been linked to virilization of XX fetuses—again, no genetic DSD is required. (PubMed)

  
  

• Rarely, aromatase inhibition during pregnancy (e.g., inadvertent exposure) can permit maternal androgens to act on an XX fetus, causing virilization. (Pediatrics)

  
  

Implication: An XX person may display male‑typical traits (from birth or at puberty) primarily due to prenatal androgen exposure, not because of a named genetic syndrome. (PubMed Central)

2) Reduced fetal androgen action in XY infants without a genetic diagnosis

Typical male‑pattern development requires adequate fetal testicular androgens during narrow “programming windows.” Non-genetic factors that reduce androgen action can yield female‑typical or less male‑typical traits in an XY infant (e.g., hypospadias, shorter anogenital distance, micropenis), even when genetic testing is nondiagnostic. (Frontiers)

• Endocrine‑disrupting chemical (EDC) exposures in pregnancy have been associated—in human observational studies and supported by animal data—with shortened anogenital distance (AGD) and other markers of reduced androgen action in male offspring; evidence is mixed in places but overall suggests risk. (PubMed Central, PubMed)

  
  

• Some population studies also associate environmental exposures or air pollution with shorter AGD in newborns, a biomarker of lower prenatal androgen signaling. (BioMed Central)

  
  

Implication: An XY person may present with female-typical features or undermasculinization primarily due to prenatal endocrine environment, not a discoverable single-gene disorder. (Frontiers)

3) Early testicular regression in utero (non-genetic loss of function)

In testicular regression syndrome, an initially present fetal testis atrophies or disappears (often attributed to a vascular event). If this occurs early enough, the XY fetus may not receive adequate androgens for typical male development, resulting in partial or even female‑typical external anatomy despite an XY karyotype—and no identifiable genetic DSD. (PubMed Central, jcrpe.org)

4) Why many cases remain “traits‑only”

Even with modern sequencing, a large fraction of DSD evaluations remain unsolved—meaning no single, named genetic diagnosis explains the phenotype. Clinical exome/panel testing in 46,XY DSD cohorts typically finds a firm diagnosis in ~20–45%, leaving most without a clear label. This underscores how intersex traits can exist without a genetic “answer.” (PubMed, PubMed Central, BioMed Central)

Concrete scenarios (XX and XY) without a classic genetic condition

XX individual with masculinizing traits (no named DSD)

• Prenatal maternal androgen excess (e.g., luteoma of pregnancy) → virilized XX genitalia at birth; later, androgen‑pattern hair growth or voice changes may persist. The person’s karyotype is XX, and no classic genetic syndrome is present. (PubMed, PubMed Central)

  
  

• Maternal medication exposure (historical danazol; rarely aromatase inhibitors) → XX virilization without a fetal genetic diagnosis. (PubMed, Pediatrics)

  
  

XY individual with feminizing/undermasculinized traits (no named DSD)

• Early testicular regression (vanishing testes) → insufficient fetal androgen → female‑typical or ambiguous external anatomy despite XY karyotype. No inherited mutation is required. (PubMed Central)

  
  

• Reduced prenatal androgen action linked to environment (EDCs, air pollution) → shorter AGD, hypospadias risk patterns reported in some studies, without a gene finding. (PubMed Central, BioMed Central)

What evaluation looks like when classic conditions are excluded

• Detailed pregnancy history (maternal virilization, tumors, medications, endocrine disorders, environmental/occupational exposures). (PubMed Central)

  
  

• Physical exam + targeted labs (AGD, gonadal hormones for age/stage) and imaging (internal reproductive structures). (PubMed Central)

  
  

• Stepwise genetics (karyotype → targeted panels → exome): helpful when positive, but expect that many individuals will remain “traits-only.” (PubMed Central)

  
  

Educational note (not medical advice): intersex traits deserve validation and appropriate care regardless of whether a named genetic condition is found. Multidisciplinary teams familiar with differences of sex development (DSD) provide the most supportive care across the lifespan. (Nature)

Plain-language takeaways

• Intersex ≠ only genetics. An XX or XY person can develop traits typical of the “other” sex without a named mutation—through prenatal hormones, loss of fetal gonadal function, or environmental factors. (Frontiers, PubMed Central)

  
  

• Undiagnosed is common. Today’s best tests still don’t find a single cause in many cases. Care should focus on the person’s real anatomy, hormones, and goals, not just the lab label. (PubMed Central)

References (selected)

1. UK guidance on initial DSD evaluation – practical, patient-centered overview. (PubMed Central)

   
   

2. Nature Reviews Endocrinology (Cools et al.) – comprehensive DSD review, care principles. (Nature)

   
   

3. Exome sequencing in 46,XY DSD – diagnosis ~35% on average; many remain unsolved. (PubMed, PubMed Central)

   
   

4. Maternal luteoma of pregnancy – androgen‑producing, can virilize XX fetuses; resolves postpartum. (PubMed, PubMed Central)

   
   

5. Medication exposures – danazol associated with XX virilization; aromatase‑inhibitor case (2023). (PubMed, Pediatrics)

   
   

6. Endocrine‑disrupting chemicals & male development – evidence base and mixed epidemiology. (Frontiers, PubMed Central)

   
   

7. AGD as a biomarker of prenatal androgen action – human data including phthalates/PM2.5 associations. (PubMed Central, BioMed Central)

   
   

8. Testicular regression (“vanishing testis”) – non-genetic loss of testicular function in utero. (PubMed Central)