Klinefelter Syndrome: What should we tell prospective parents?

• Published in: Prenatal diagnosis Vol. 43; no. 2; pp. 240 - 249
• Main Authors: White, Mary, Zacharin, Margaret R., Fawcett, Susan, McGillivray, George
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-02-2023
• Subjects: Adolescent; Aneuploidy; Children; Female; Genetic counseling; Genetic screening; Humans; Infant, Newborn; Infertility; Klinefelter Syndrome - diagnosis; Klinefelter Syndrome - epidemiology; Klinefelter Syndrome - genetics; Klinefelter's syndrome; Male; Noninvasive Prenatal Testing; Parents; Parturition; Pregnancy; Prospective Studies; Puberty; Sex Chromosome Aberrations; Sex chromosomes
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.6250

Klinefelter syndrome (KS) or 47,XXY is the most common sex chromosome aneuploidy (SCA), occurring at a prevalence of 1 in 600 male pregnancies. Historically, only 25% of individuals with KS came to medical attention, for a range of issues across the life course including under‐virilisation at birth, developmental and social concerns in childhood, absence, delay or arrest of puberty in adolescence or infertility in adulthood. Our understanding of the phenotypic spectrum of KS has been largely influenced by this ascertainment bias. With increasing uptake of antenatal noninvasive prenatal testing (NIPT), a corresponding increase in identification of KS has been documented. Population‐based longitudinal data from infancy to adulthood on these individuals is lacking, which impedes balanced antenatal genetic counselling and raises issues for prospective parents and clinicians alike.
Key points
What is already known about this topic?
Prior to the widespread availability of NIPT, only 25% of individuals with Klinefelter Syndrome were detected on the basis of postnatal clinical features.
With increasing uptake of NIPT, increasing numbers of sex chromosome aneuploidy will be detected in countries where sex chromosomes are included in this test.
Antenatal counselling for prospective parents after a presumptive or confirmed case of Klinefelter Syndrome is challenging due to ascertainment bias of existing data.
What does this study add?
An awareness of the limitations of current data is crucial to allow a balanced approach to antenatal counselling.
Involvement of paediatric endocrinologists or paediatricians in the antenatal counselling process will facilitate this balanced approach.
The role of peer support and advocacy networks in this process should be explored.
Highlights a need for high quality longitudinal data to report on pregnancy outcomes and phenotypes of infants born with antenatally diagnosed SCA.