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Non-invasive prenatal testing (NIPT) uses cell-free DNA (cfDNA) in maternal blood to screen for fetal aneuploidy. Maternal and fetal cfDNA are both present in maternal blood; however, fragmentation patterns are different. This allows the fetal fraction to be identified and screened for autosomal chromosome aneuploidy, specifically Trisomy 13, 18, and 21. Although not currently recommended for routine use, NIPT can also be used to screen for sex chromosome abnormalities. This practice is increasingly common, as allows parents to determine the baby’s sex earlier than ultrasound. Klinefelter syndrome (XXY karyotype) is one sex chromosome aneuploidy that NIPT may recognize. Currently, mean age of diagnosis of Klinefelter syndrome is 30 years, with up to 75% of cases never diagnosed. Thus, increased NIPT use could result in a major shift in its recognition. We present two cases of Klinefelter syndrome diagnosed by NIPT.
PATIENT PRESENTATION, DIAGNOSTICS, PLAN OF CARE
Case 1: A 29-year-old, gravida 4 para 3 pregnant woman was curious about her fetus’ sex and requested NIPT, which returned with a karyotype of XXY. A 2670-gram male infant was born without dysmorphic features and normal genitalia with descended testes. Fluorescent in situ hybridization and blood chromosomes confirmed XXY karyotype. He was discharged with follow up by genetic counselors and close monitoring for developmental delays.
Case 2: A 19-year-old, primigravid woman had NIPT at 12 weeks gestation that revealed a fetal karyotype of XXY, confirmed by amniocentesis at 14 weeks gestation. A 2000-gram male infant was born without dysmorphic features and normal genitalia with descended testes. Fluorescent in situ hybridization and blood chromosomes confirmed XXY karyotype. He was discharged with follow up by genetic counselors and close monitoring for developmental delays.
DISCUSSION AND IMPLICATIONS FOR PRACTICE
NIPT allows for earlier detection of Klinefelter syndrome, as occurred in the cases described; however, whether this should be routine remains contested. For parents, early recognition could cause undue stress. Given the importance of early intervention for learning disabilities, developmental delays, and neuropsychiatric disorders—all of which Klinefelter syndrome patients are at higher risk for—one could argue for increased NIPT screening. Despite controversy over the necessity of its universality, with the increase in usage of NIPT, fortuitous diagnoses will continue to occur. This indicates a need for the medical community to define guidelines for early management and observation of patients with Klinefelter syndrome.
Craven, Sarah and Zach, Terence, "Two Patients With Klinefelter Syndrome Fortuitously Diagnosed by Non-Invasive Prenatal Test" (2022). Child Health Research Institute Pediatric Research Forum. 43.