Prenatal and Postnatal Prevalence of Klinefelter Syndrome: A National Registry Study

Abstract

The objective of this study was to describe the prevalence of Klinefelter syndrome (KS) prenatally and postnatally in Denmark and determine the influence of maternal age. All chromosomal examinations in Denmark are registered in the Danish Cytogenetic Central Registry. Individuals with KS diagnosed prenatally or postnatally were extracted from the registry with information about age at the time of diagnosis and mother's age. In the period 1970-2000, 76,526 prenatal examinations on male fetuses resulted in the diagnosis of 163 fetuses with KS karyotype, corresponding to a prevalence of 213 per 100,000 male fetuses. Standardization according to maternal age resulted in a prevalence of 153 per 100,000 males. Postnatally, 696 males of 2,480,858 live born were diagnosed with KS, corresponding to a prevalence among adult men of approximately 40 per 100,000. Less than 10% of the expected number was diagnosed before puberty. Advanced maternal age had a significant impact on the prevalence. KS is severely underdiagnosed in Denmark. Only approximately one fourth of adult males with KS are diagnosed. There is a marked delay in diagnosis of the syndrome. A delay in treatment with testosterone may lead to decreased muscle and bone mass with subsequent risk of osteoporosis.

Leydig cell transplantation restores androgen production in surgically castrated prepubertal rats

“…An estimated one in 200 children suffers from androgen deficiency worldwide [1], causes of which include congenital abnormalities, trauma, infections and tumour growth [2]. Further, prepubertal testicular dysfunction, if improperly treated or left untreated, can lead to primary hypogonadism and altered sexual development.…”

Assessing the risks and benefits of diagnosing genetic conditions with variable phenotypes through population screening: Klinefelter syndrome as an example

“…& A variable phenotype, ranging from "near-normal" (or seemingly clinically benign) to significantly affected & A strong psychosocial component, also variable but not usually including intellectual disability & Interventions of uncertain benefit, available from early childhood but for which the effect on later outcomes has not been fully established KS is a common genetic condition (47XXY) affecting males with an estimated prevalence of 1:660 (Bojesen et al 2003)-equating to over 640,000 males with KS across Europe. The additional X chromosome results in a spectrum of clinical features ranging from infertility, small testes, testosterone deficiency, breast development, and decreased facial and pubic hair, to varying levels of specific cognitive, social, behavioural and learning difficulties (Simpson et al 2003).…”

“…The additional X chromosome results in a spectrum of clinical features ranging from infertility, small testes, testosterone deficiency, breast development, and decreased facial and pubic hair, to varying levels of specific cognitive, social, behavioural and learning difficulties (Simpson et al 2003). Despite these features, up to 70% of KS remains undiagnosed and of those that are detected, diagnosis is not usually made until later in adulthood (Bojesen et al 2003). As only the most florid cases tend to be detected by current postnatal surveillance (Abramsky and Chapple 1997), this may lead to the perception that KS is rare and that all patients exhibit a 'classic textbook' phenotype.…”

Determinants of male health: the interaction of biological and social factors

“…This condition is also associated with variable learning difficulties and behavioural disturbances [17,18]. Although a careful assessment of testicular size at the average age of conclusion of normal puberty would establish the diagnosis, about 60% of such men are never diagnosed [19].…”