Promoting Early Genetic Screening for 47,XXY Based On Early Intervention and Emerging Treatment Options

Abstract

Background: 47,XXY commonly known as Klinefelter syndrome (KS) is the most common male sex chromosome aneuploidy. The syndrome is characterized by hypotonicity, developmental delays, learning disabilities, and psychosocial problems during infancy/childhood and low testosterone production (hypogonadism) in adolesence/adulthood. Untreated, adolescents and adults may develop gynecomastia, osteoporosis and most commonly, infertility. The current standard of care offers treatment for KS at the onset of puberty for boys following molecular diagnosis. However, most males are not diagnosed until adulthood, and may only present when seeking medical attention for infertility. Purpose: The purpose of this presentation is to propose early genetic screening for males at birth specifically for KS, which is not currently part of newborn screening. Such screening may potentially capture a higher proportion of males with KS. Description of Topic: Encouraging practitioners to promote early genetic screening for all males at birth for KS, may identify more boys with this genetic disorder. Early identification can prompt early intervention services aimed at treating some of the problems common to KS in infancy, childhood and adolescense. The benefits of treatment can be discussed with parents to support informed choices. Currently, discussing the pros and cons of emerging treatment with parents is not part of the standard of care. Clinical Implications: Boys diagnosed with KS in infancy may benefit from early intervention. In particular, developmental delays in boys with KS may be identified early and treatment initiated - rather than taking a watchful waiting approach. Parents and families may benefit from referral to centers specializing in KS that offer treatment outside the traditional approaches and conduct clinical trials.