ESPE Abstracts

Introduction: Differentiation of the external genitalia depends on serum androgen concentrations in the foetal life. The classic form of Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most frequent cause of female genital ambiguity. It is an autosomal recessive disorder due to CYP21A2 mutations that are classified in groups based on their in vitro residual enzymatic activity. The phenotype usually is predicted by the less severe mutation and the virilisation usually correlates to the degree of enzyme deficiency. Clinically 21OHD is classified in Classic, comprising the salt-wasting (SW) and the simple virilising (SV) forms, and nonclassic (NC) form.

Description of the cases: We present data obtained at the 21OHD diagnosis of six female children. The degree of virilisation of the external genitalia was described using Prader criteria and varied among stage 1 (isolated clitoromegaly), stage 2 (clitoromegaly and partial labioscrotal fusion) and stage 3 (clitoromegaly and total labioscrotal fusion with a perineal opening). The molecular study showed that all children carried a salt-wasting and a simple virilising mutation in either allele (Allele-SW and Allele-SV), being, therefore, the predicted phenotype SV. The age at diagnosis in months (Age), the bone age in years (BA), the genital virilisation according to Prader criteria (Prader), the serum levels of 17OHP in ng/mL (17OHP), mutations (Allele-SW and Allele-SV) are presented below: ACSC 44m; BA 5.2y; Prader 2; 17OHP 79.5; Allele-SW c.-315C>T; c.290-13A/C>G; Allele-SV c.-103A>G; p.Ile172Asn. EVSC 31m; BA 5.6y; Prader 1; 17OHP 158.8; Allele-SW c.-315C>T; c.290-13A/C>G; Allele-SV c.-103A>G; p.Ile172Asn. ARSC 7m; Prader 3; 17OHP 82.0; Allele-SW large gene conversion; Allele-SV p.Ile172Asn. AJRM 19m; BA 3.8y; Prader 3; 17OHP 224.4; Allele-SW p.Arg356Trp; Allele-SV p.Ile172Asn. ACAS 23m; BA 5.1y; Prader 1; 17OHP 206.8; Allele-SW p.[Leu308Phefs*6;Gln318*; Arg356Trp]; Allele-SV p.Ile172Asn. LFTR 27m; BA 5.3y; Prader 1; 17OHP > 50.0; Allele-SW p.[Gln318*; Arg356Trp]; Allele-SV p.Ile172Asn.

Comments: We report six cases of CAH due to 21OHD, all with the classic, simple virilising form confirmed by molecular study, whose discrete genital virilisation was not identified at birth by the paediatrician. According to the relatives, all of them had clitoromegaly and in 3 cases there was also labial fusion at birth. Through this presentation, we would like to draw attention to the importance of a careful examination of the external genitalia at birth, in order to identify small alterations and obtain early 21OHD diagnosis.