Uncontrolled hypertension in siblings: an unsuspected diagnosis

Hypertension in the young is defined as the occurrence of elevated blood pressure in patients aged <40 years. It is unusual for hypertension to be present before the second decade of life and more so in a pair of siblings. This study aimed to report a case of a sibling pair (18- and 16-year-olds), reared as females, who presented with primary amenorrhea and resistant hypertension. The initial presentation was hypertension. The siblings were treated with escalating doses of antihypertensive agents, including calcium channel blockers, beta-blockers, and diuretics, with suboptimal control. Primary amenorrhea led to an endocrine referral, and detailed evaluation revealed obesity, acne, atypical external genitalia, and palpable gonads. The hormonal panel showed low cortisol, elevated adrenocorticotropic hormones, and progesterone, along with hypokalemia, raising the possibility of a rare congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency. The siblings had a 46 XY karyotype, and CYP17A1 gene sequencing revealed a homozygous deletion of c.157_159TTC of the phenylalanine codon (thymine-thymine-cytosine) at amino acid position 54 (p.Phe54del) in exon 1, confirming our diagnosis. The siblings were treated with glucocorticoids and spironolactone, which remarkably improved the blood pressure, coupled with the gradual withdrawal of all antihypertensive agents. Psychological evaluation established a preference for the female gender. The siblings underwent bilateral gonadectomy with vaginoplasty, along with estrogen replacement therapy. Hypertension in the young suggests a secondary etiology, including renovascular and endocrine conditions. Our report highlights the CYP17A1 gene mutation, a rare form of monogenic hypertension presenting in phenotypical females with a male genotype.