Pentasomy 49,XXXXY Diagnosed in utero: Case Report and Systematic Review of Antenatal Findings

Abstract

Objectives: Pentasomy 49,XXXXY is a rare sex chromosome polysomy usually diagnosed postnatally by the combina- tion of mental retardation, facial dysmorphism, and genital, cardiac and skeletal malformations. Prenatal detection of 49,XXXXY is unusual and may be incidental due to non-specific ultrasound (US) findings. We report a case of 49,XXXXY diagnosed prenatally and present a literature review of the few prenatally diagnosed cases. Methods: We searched the PubMed electronic database without year and language restriction, using the keywords ‘Prenatal’, ‘Diagnosis’, and ‘49,XXXY’, performing a systematic review. Results: We report a 35-year-old patient with normal first-trimester US but increased combined risk for trisomies 18 and 13. Amniocentesis at 16 weeks of gestation revealed a 49,XXXXY karyotype. Pregnancy was terminated at 19 weeks’ gestation, and a male fetus with facial dysmorphism and hypospadia was delivered. A total of 12 articles were identified in the systematic review. All were case reports and dated from 1980 until 2008. The mean maternal age was 34.8 years (range 30–41). The most common prenatal US feature was cystic hygroma, present in 5 cases. Hypogenitalism was the most common macroscopic clinical feature identified after pathology examination in 7 cases. In 2 cases, there was an increase in first-trimester combined risk for trisomy 21. Conclusions: Pentasomy 49,XXXXY is associated with a variety of non-specific US findings, of which cystic hygroma was the commonest. No specific sequence of findings could be identified in this review.

False Low-Risk Single Nucleotide Polymorphism–Based Noninvasive Prenatal Screening in Pentasomy 49,XXXXY

“…Clubfoot was previously noted in four reports. 5 Micropenis was also previously reported. 5 These findings are ultimately nonspecific and should trigger further investigation, including invasive diagnostic testing with prenatal chromosome microarray, as in this case.…”

“…However, reported prenatal features described in the literature include cystic hygroma, microgenitalia, clubfoot, epignathus, nonimmune hydrops, and hypoplastic right heart syndrome. 5 Confirmatory prenatal diagnosis relies on amniocentesis and fetal chromosomal studies.…”

Close but not quite: Two cases of sex chromosome aneuploidies outside the scope of cell free DNA screening

“…We recommend that patients receive counseling on the utility of prenatal diagnosis in the setting of abnormal cfDNA screening results for sex chromosome trisomies. This should be emphasized in cases with ultrasound findings including but not limited to ambiguous genitalia, penile hypoplasia, abnormal posturing of the lower extremities, radioulnar synostosis, cystic hygroma, and even nonimmune hydrops fetalis, as such findings have been previously described with sex chromosome tetrasomy and pentasomy conditions . However, a lack of associated ultrasound findings or major dysmorphic features does not altogether eliminate the concerns for an underlying sex chromosome aneuploidy.…”

Prenatal presentation of 49,XXXXY syndrome

“…Reports of the prenatal presentation of 49,XXXXY are scarce. Prior literature describes cystic hygroma and clubfoot as the most commonly encountered ultrasound abnormalities, when sonographic features are present . Of note, the majority of sex chromosome aneuploidies (SCAs) do not present with anomalies or genital discordance on ultrasound.…”