Objective: To describe and discuss our experience of patients with congenital adrenal hyperplasia (CAH) conceived via assisted reproduction techniques (ART).
Design: Case reports.
Setting: Tertiary hospitals and a CAH molecular diagnosis reference laboratory belonging to one of these.
Patient(s): Five patients with CAH (with 21-hydroxylase deficiency [21OHD]) conceived via homo/heterologous ART with egg or sperm donations.
Intervention(s): Molecular diagnosis following DNA analysis of patients, parents, and siblings, including direct analysis of the gene (polymerase chain reaction/allele-specific hybridization), Southern analysis (for gene deletions and duplications), semiquantitative primer extension (to confirm duplications), complementary sequencing, and microsatellite analysis to confirm allele segregation.
Main outcome measure(s): Genotype identification and segregation analysis of alleles. Clinical evaluation of patients.
Result(s): Three children (two girls, one boy) with classic neonatal forms of CAH (salt wasting and severe virilization) and two with nonclassic forms (two girls, one compound heterozygous with a severe mutation who showed clinical signs at 3.5 years of age) were born to parents who used ART. All showed segregated 21OH gene mutations. The respective genotypes were: 655G/655G, Q318X/Q318X,R356W, gene deletion hybrid with break point at exons 3-4/8 bp deletion at exon 3, 655G/V281L, and V281L/V281L. The severe mutations in the donated gametes were 655G and Q318X-R356W.
Conclusion(s): As a common, infertility-related and prenatal treatment-susceptible recessive genetic disease, 21OHD genotyping should be considered in ART.