Insight into the 8p23.1 duplication syndrome: Case report of a young women with infertility

Objective: To report the case of a young woman with repeated conception failure, whose karyotype showed an unbalanced complex chromosomal rearrangement involving a large duplication harboring >115 genes and overlapping the 8p23.1 duplication syndrome region. The 8p23.1 duplication syndrome results from a tandem duplication on the short arm of chromosome 8 containing the 4 genes (GATA4, TNKS, SOX7, XKR6) responsible for the most common phenotypic features: developmental delay/learning disabilities, congenital heart disease and dysmorphism.

Design: Case report and review of the literature.

Setting: American University of Beirut Medical Center, department of Pathology and Laboratory medicine.Patient(s): Young woman referred to the genetic clinics for the workup of secondary idiopathic infertility with multiple unsuccessful inseminations and in vitro fertilizations.

Interventions: Peripheral blood karyotype analysis from the patient and her parents. Elucidation of the CCR required whole chromosome painting Fluorescent in Situ Hybridization and Chromosomal Microarray.

Main outcome measures: The few published reports on 8p23.1 duplication syndrome (<50 cases) describing carriers reveal a wide range of phenotypic consequences with heterogeneous severity. The main outcome is to further understand this syndrome.

Results: Chromosomal microarray analysis detected a large (12Mb) pathogenic Copy Number Variant (CNV) at 8p23.3p23.1, overlapping the 8p23.1 duplication syndrome region. This CNV, classified as pathogenic, was shown to carry little significance in our patient.

Conclusions: 8p23.1 duplication syndrome display a variable expressivity, ranging from overt syndromic features to minimal effect on the phenotype as shown in this case. Interpretation of prenatal detection of 8p23.1 duplication especially in preimplantation diagnosis is thus challenging. Nevertheless, this case emphasizes the importance of genetic testing in infertile patients displaying a normal phenotype.