Prepubertal gynaecomastia may be due to increased oestrogen resulting from excessive aromatase activity in extra glandular tissues. CYP19A1 gene on chromosome 15q21.2 encodes aromatase, the key enzyme for oestrogen biosynthesis. Tissue-specific promoters regulating the expression of aromatase activity have been demonstrated in placenta, ovary, testes, brain, skin fibroblasts and adipocytes. Mutations involving aromatase cytochrome P450 (P450arom) have been reported in familial aromatase excess syndrome. We present a prepubertal boy with gynaecomastia who was not found to have any mutation in the coding part of the aromatase gene.
An 8 year-old boy presented with slowly progressive bilateral gynaecomastia. His birth and previous childhood history was unremarkable. On initial assessment, his height and weight were within the 75th98th centile and BMI 20.1(98th centile). He had mild truncal adiposity, bilateral gynaecomastia (stage 2), early signs of adrenarche (hyperhydrosis and body odour) but absence of any testicular enlargement. Routine serum/blood chemistry was normal. He had persistently raised levels of Oestradiol (33, 40 and 37 pmol/l; normal: 1535) in the presence of undetectable testosterone levels of <0.1 nmol/l (9.127.8). Bone was advanced by 3 years. There was absence of any family history of gynaecomastia.
The finding of raised oestradiol in presence of low testosterone levels in this child with prepubertal gynaecomastia and advanced bone age suggested a diagnosis of aromatase excess syndrome, which prompted further investigations into mutations of the CYP19 gene. Genetic studies did not show any mutations of the CYP19 A1gene, but confirmed the presence of the allele (TTTA) 11 in a homozygous state and located in intron 4 of the CYP19A1 gene. This allele has been associated with high aromatase activities, which might explain the clinical phenotype in our case.
Further studies may be undertaken to look at mRNA P450 aromatase expression in the adipocytes of this child.