Clinical, cytogenetic, and genomic analyses of an Ecuadorian subject with Klinefelter syndrome, recessive hemophilia A, and 1;19 chromosomal translocation: a case report

Anibal Gaviria; Santiago Cadena-Ullauri; Francisco Cevallos; Patricia Guevara-Ramirez; Viviana Ruiz-Pozo; Rafael Tamayo-Trujillo; Elius Paz-Cruz; Ana Karina Zambrano

doi:10.1186/s13039-022-00618-w

Clinical, cytogenetic, and genomic analyses of an Ecuadorian subject with Klinefelter syndrome, recessive hemophilia A, and 1;19 chromosomal translocation: a case report

Mol Cytogenet. 2022 Sep 5;15(1):40. doi: 10.1186/s13039-022-00618-w.

Authors

Affiliations

¹ Laboratorio de Genética Molecular, Centros Médicos Especializados Cruz Roja Ecuatoriana, Quito, Ecuador.
² Hemocentro Nacional, Cruz Roja Ecuatoriana, Quito, Ecuador.
³ Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador.
⁴ Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador. anazambrano17@hotmail.com.

^# Contributed equally.

Abstract

Background: Hemophilia A is considered one of the most common severe hereditary disorders. It is an X-linked recessive disease caused by a deficiency or lack of function of the blood clotting factor VIII. Klinefelter syndrome is a genetic disorder that affects male individuals due to one or more extra X chromosomes, present in all cells or with mosaicism. The aneuploidy is due to either mitotic or meiotic chromosome non-disjunction. Chromosomal translocations are a group of genome abnormalities in which a region or regions of a chromosome break and are transferred to a nonhomologous chromosome or a new location in the same chromosome.

Case presentation: Our subject was born in Ecuador at 36 weeks of gestation by vaginal delivery. At 3 months old, the Factor VIII activity measure showed a 23.7% activity indicating a diagnosis of mild hemophilia A. At 1 year old, the karyotype showed an extra X chromosome, consistent with a diagnosis of Klinefelter syndrome, and a translocation between the long arms of chromosomes 1 and 19, at positions q25 and q13, respectively.

Conclusions: Klinefelter syndrome and hemophilia are a rare combination. In the present case report, the subject presents both, meaning that he has inherited one X chromosome from the father and one X chromosome from the mother. Since the father has severe hemophilia A; and the subject presents a below 40% Factor VIII activity, a skewed X inactivation is suggested. Additionally, the proband presents a translocation with the karyotype 47,XXY,t(1;19)(q25;q13). No similar report with phenotypic consequences of the translocation was found. The present report highlights the importance of a correct diagnosis, based not only on the clinical manifestations of a disease but also on its genetic aspects, identifying the value of integrated diagnostics. The subject presents three different genetic alterations, Klinefelter syndrome, hemophilia A, and a 1;19 chromosomal translocation.

Keywords: Chromosomal translocation; Hemophilia A; Klinefelter syndrome.