Genetic testing of XY newborns with a suspected disorder of sex development

Abstract

Considering that children and adults with DSD may be at risk of several comorbidities a clear aetiological diagnosis will guide further management. To date, a firm diagnosis is not reached in over half of the cases of 46,XY DSD. Whilst it is likely that improved diagnostic resources will bridge this gap in the future, the next challenge to the clinical community will be to show that such advances will result in an improvement in clinical care.

GENETICS IN ENDOCRINOLOGY: Approaches to molecular genetic diagnosis in the management of differences/disorders of sex development (DSD): position paper of EU COST Action BM 1303 ‘DSDnet’

“…Reaching a molecular diagnosis is important as it may inform patient management in relation to possible gender development, assessment of adrenal and gonadal function, gonadal cancer risk, associated morbidity as well as long-term outcomes. Determining the aetiology is often useful for families, as it provides information about risk of recurrence ( 8 , 9 , 10 ).…”

Prenatal ultrasound finding of atypical genitalia: Counseling, genetic testing and outcomes

“…The extragenital anomalies in 62% of patients were usually the reason for referral and exceed the 30%-41% in previous postnatal studies. 6,7 It emphasizes the importance of thorough US-screening for additional anomalies possibly associated with serious congenital conditions. Some bias cannot be ruled out, as pregnant women are more likely to be referred to a specialized center when atypical genitalia are accompanied by additional anomalies.…”

“…[2][3][4][5] For genital anomalies, the frequency of additional anomalies is largely unknown. It was estimated to be 30% for males with hypospadias in a study that included fetal growth restriction (FGR) as an additional anomaly 6 and 41% overall in retrospective cohorts of neonatal ambiguous genitalia. 7 These were retrospective cohort studies in DSD-centers; the frequency of additional anomalies in the prenatal setting remains unknown.…”

Under-reported aspects of diagnosis and treatment addressed in the Dutch-Flemish guideline for comprehensive diagnostics in disorders/differences of sex development

“…When couples opt for invasive prenatal diagnosis, the genetic analysis usually involves an (SNP)-array. It was recently estimated that >30% of individuals who have a DSD have additional structural anomalies, with cardiac and neurological anomalies and fetal growth restriction being particularly common 27 28. If additional anomalies are seen, the geneticist can consider specific gene defects that may underlie a known genetic syndrome or carry out NGS.…”

“…It was recently estimated that >30% of individuals who have a DSD have additional structural anomalies, with cardiac and neurological anomalies and fetal growth restriction being particularly common. 27 28 If additional anomalies are seen, the geneticist can consider specific gene defects that may underlie a known genetic syndrome or carry out NGS. NGS-based techniques have also now made their appearance in prenatal diagnosis of congenital anomalies.…”