Pre‐ and postnatal findings in trisomy 17 mosaicism

Abstract

Trisomy 17 mosaicism is one of the rarest autosomal trisomies in humans. Thus far, only 23 cases have been described, most of them detected prenatally. In only five instances has mosaicism been demonstrated in lymphocytes and/or fibroblasts postnatally, and only in these have multiple congenital anomalies (MCA), facial dysmorphisms, and mental retardation been reported. Patients with trisomy 17 mosaicism at amniocentesis and a normal karyotype in blood and fibroblasts (n = 17) were always healthy. Here, we report on pre- and postnatal clinical, cytogenetic, molecular-cytogenetic, and molecular findings in four patients with trisomy 17 mosaicism. The first case was detected in cultured but not in short-term chorionic villi and amniocytes. Due to MCA on prenatal ultrasound examination the pregnancy was terminated. The second patient is a 13-month-old healthy boy, in whom low level trisomy 17 mosaicism was detected in cultured chorionic villi only. The third patient is a 2-year-old girl with growth retardation, developmental delay, MCA, and trisomy 17 mosaicism in amniocytes, fibroblasts, and placenta, but not in blood and buccal smear. The fourth patient is a 9-year-old boy with growth and mental retardation, sensoneurinal hearing loss, and MCA. Cytogenetic analyses showed trisomy 17 mosaicism in amniocytes, skin fibroblasts, and urinary sediment cells, whereas in blood and buccal smear a 46,XY karyotype was found. Molecular investigations in all four cases indicated biparental inheritance of chromosome 17. Formation of trisomy was most likely due to a maternal meiosis I error in Patient 1 and a postzygotic non-disjunction of the paternal chromosome 17 in Patient 4. Cerebellar malformations, reported in two cases from the literature and in two reported here may be a specific feature of trisomy 17 mosaicism. Since the aberration has rarely been reported in lymphocytes, chordocentesis is not indicated in prenatal diagnosis. Prenatal genetic counseling for trisomy 17 mosaicism in chorionic villi or amniocytes should consider that the clinical significance remains uncertain.

Human Embryonic Stem Cells as Models for Aneuploid Chromosomal Syndromes

“…Ultrasonographic and pathological studies performed on fetuses with trisomy 13 revealed a severe compromise on brain, heart, and placenta as predicted by the EB model [29–31]. Likewise, fetuses and children with mosaic trisomy 17 showed delayed brain growth and/or cognitive function impairment in accordance to the in vitro model [11]. In view of the high correlation between the predicted alterations by the EB model, the teratoma model and the observations in patients, we can suggest that in vitro differentiation into EBs is a useful tool to study tissue alteration in aneuploidies.…”

“…Complete trisomy 17 has never been reported in a live birth. In rare cases, a mosaic of normal euploid cells and cells with trisomy 17 are viable [11]. The patients carrying the trisomy have developmental delay and mental retardation along with multiple neurological disorders.…”

Prenatal testing for uniparental disomy: indications and clinical relevance

“…If only a normal cell line is found on amniocentesis or cordocentesis, the question of UPD arises, but one has to keep in mind that mosaicism for some chromosomes (e.g. 17 and 20) might be found on CVS and/or amniocentesis, but not on cordocentesis, and the fetus might still be trisomic and clinically affected20. Testing for UPD is indicated if chromosome 14 or 15 is trisomic.…”

The Rare Regular Trisomy 17: Frequency and Phenotypic Portrait

“…However, the level of mosaicism varies greatly in different tissues and does not correlate with prognosis [11][12][13][14][15][16][17][18][19][20]. Molecular genetic analysis has confirmed mosaic T17 in several cases resulted from postzygotic mitotic errors in distribution of maternal chromosome 17 [13,16,18]. Parental origin of extra chromosome 17 was determined with genome-wide SNP-microarray molecular genetic analysis [11].…”