Congenital adrenal hyperplasia (CAH) is a hetero genous group of hereditary autosomal recessive disorders characterized by deficient synthesis of adrenal steroid hormones. It is the most frequent cause of adrenal insufficiency and ambiguous genitalia in infancy. The disease is caused, in most cases (more than 90%), by defects in the gene coding for steroid 21 hydroxylase, CYP21 [1,2].

Classical forms of CAH can manifest as lethal miner alocorticoid and cortisol insufficiency, or as a simple vir ilation. The late onset form presents in girls and young women with only hirsutism and oligoamenorrhea, where as cryptic forms have no clinical symptoms and are detected only when family studies are performed [3-7]. Such heterogeneity has imposed difficult questions about the genetic background of the disease.

The incidence of different forms of the disease varies in different populations. Throughout Caucasian and Oriental populations the average incidence is 1:15,000 newborns. In general, three-quarters of the affected children have the salt-wasting form and only 20% have simple virilization.

The CYP21 gene is frequently modified through mutations and conversions from the very homologous pseudo gene CYP21P [8-10]. A strong relation of genotype to phenotype exists. Aberrant splicing in intron 2 at nucleotide (nt) 656, an 8 bp frameshift deletion at codons 111-113, a thymine insertion at codon 306, a nonsense mutation at codon 318, and a single base substitution at codon 356, result in a complete inactivation of 21-hydroxylase and are found in the severe classical form of salt-wasting disease [3-5]. A single base change in exon 1 at codon 30, in exon 3 at codon 105, in exon 7 at codon 281, and in exon 10 at codon 453, are associated with the milder non classical form of CAH, in which there is only partial loss of 21-hydroxylase activity [4,6]. The simple virilization found in some CAH patients is associated with a mutation in exon 4 at codon 172, which abolishes 21-hydroxylase activity [4,7]. Combination of these mutations can cause different phenotypes [11,12].

We present a young girl who had a combination of severe and mild mutations and presented as simple viriliza tion and whose parents have CAH which manifested only as a difficulty to conceive.