Non-Invasive Prenatal Screening: The First Report of Pentasomy X Detected by Plasma Cell-Free DNA and Karyotype Analysis

Abstract

Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX) and is probably due to a nondisjunction during the meiosis. So far, only five cases prenatally diagnosed were described. The main features in 49,XXXXX karyotype include severe intellectual disability with delayed speech development, short stature, facial dysmorphisms, osseous and articular abnormalities, congenital heart malformations, and skeletal and limb abnormalities. Prenatal diagnosis is often difficult due to the lack of a clear echographic sign like nuchal translucency (NT), and mostly cases were postnatally described. We report the first case of a 49,XXXXX female that was detected by non-invasive prenatal screening (NIPS), quantitative fluorescence polymerase chain reaction (QF-PCR) and a fetal karyotype.

A 12-year Life History of a Girl with Profound Intellectual Disability and Leukoencephalopathy: A Rare Clinical Presentation of X Chromosome Pentasomy

“…Polysomy 49, XXXXX is a sporadic chromosomal disease ( 11 ). The disorder occurs due to occasional errors during meiosis in one of the parents, which is referred to as nondisjunction ( 2 , 12 ). Non-disjunction is a process that occurs during meiosis, where chromosomes fail to separate properly, resulting in parental gametes with either more or less than the normal haploid number of chromosomes ( 3 ).…”

“…Chromosomal aberrations are a frequent cause of mental disability, accounting for 15% of all cases ( 1 , 2 ). Diagnosis of chromosomal forms of mental disability is based on a complex of indicators obtained through clinical and cytogenetic examination ( 3 ).…”

“…Pentasomy X-chromosomal anomaly affects only girls and is characterized by five instead of two X-chromosomes, leading to a karyotype of 49, XXXXX ( 5 ). The disorder occurs due to occasional errors during reproductive cell division in one of the parents ( 2 ). The natural frequency of X-pentasomy is currently unknown due to its rarity, varied phenotype, and accompanying symptoms.…”

Manifestaciones bucales en un paciente pediátrico con pentasomía x. Reporte de un caso

“…To our knowledge from 25 to 30 cases have so far been reported, then an approximate incidence of 1 in 85.000 was reported comparing to 49,XXXXY syndrome in male live births. Other numerical abnormalities of the sex chromosomes such as 47,XXX, 47,XXY, 47,XYY and 45,X are relatively common, and occur in approximately 1 of 400 live births ( 2,4,5 ). Pentasomy X significantly impacts systems and organs, facilitating developmental delays.…”

“…According to buccal findings, few and ambiguous manifestations are reported. Only features mentioned include prominent philtrum, cupid's bow upper lip 6 , high-arched palate, facial asymmetry 7 , multiple abnormalities of craniofacial skeleton 8 , serious dental anomalies 9 , facial dysmorphisms 4 , 10 or deformed face 3 .…”