Familial hyperaldosteronism type I is caused by an unequal crossover of 11β-hydroxylase (
CYP11B1) and
aldosterone synthase (
CYP11B2) genes, giving rise to a chimeric
CYP11B1/
CYP11B2 gene (CG). We describe a family carrying a CG with high levels of free
18-hydroxycortisol but low prevalence of primary
aldosteronism (PA) and an atypical CG inheritance pattern in a family of 4 generations with 16 adults and 13 children, we measured the arterial blood pressure, serum
aldosterone, and plasma
renin activity and then calculated the serum
aldosterone:plasma
renin activity ratio and urinary free
18-hydroxycortisol. We identified the CG by long-extension PCR and predicted its inheritance pattern. The CG was found in 24 of 29 subjects (10 children and 14 adults). In CG+ patients,
hypertension and high
18-hydroxycortisol were prevalent (83% and 100%, respectively). High serum
aldosterone:plasma
renin activity ratio was more frequent in pediatric than adult patients (80% versus 36%; P<0.001). An inverse association between serum
aldosterone:plasma
renin activity ratio and age was observed (r=-0.48; P=0.018). Sequence analysis identified the
CYP11B1/
CYP11B2 crossover in a 50-bp region spanning intron 3 of
CYP11B1 and exon 4 of
CYP11B2. The CG segregation differs from an autosomal disease, showing 100% of CG penetrance in generations II and III. Statistical analysis suggests that inheritance pattern was not attributed to random segregation (P<0.001). In conclusion, we describe a family with an atypical
CYP11B1/
CYP11B2 gene inheritance pattern and variable phenotypic expression, where the majority of pediatric patients have primary
aldosteronism. Most adults have normal
aldosterone and
renin levels, which could mask them as essential hypertensives.