Trisomy 7 mosaicism prenatally misdiagnosed and maternal uniparental disomy in a child with pigmentary mosaicism and Russell– Silver syndrome

Abstract

Prenatal diagnosis of true mosaic trisomy 7 is rare in amniotic fluid and can be misinterpreted as pseudomosaic. The phenotype is highly variable and may be modified by a maternal uniparental disomy of chromosome 7 leading to mild Russell-Silver syndrome (RSS). We report here the third postnatal case of mosaic trisomy 7 with maternal uniparental disomy of chromosome 7 in a boy presenting a mild RSS. Fetal karyotype performed in amniocentesis for intrauterine growth retardation was considered normal. Mosaic trisomy 7 was diagnosed after birth, on fibroblasts karyotype performed for blaschkolinear pigmentary skin anomalies and failure to thrive. Maternal uniparental disomy of chromosome 7 was observed in blood sample. Retrospectively, trisomic 7 cells were identified in one prenatal long-term flask culture revealing a prenatal diagnosis failure. This report emphasizes the difficulty of assessing fetal mosaicism and distinguishing it from pseudomosaicism in cultured amniocytes. It is important to search for uniparental disomy as an indirect clue of trisomy 7 mosaicism and a major prognosis element. Although there are only few prenatal informative cases, detection of trisomy 7 in amniocentesis appears to be associated with a relatively good outcome when maternal uniparental disomy has been ruled out.

Mosaic upd(7)mat in a patient with Silver–Russell syndrome

“…These findings, together with the normal karyotype in lymphocytes, indicated mosaic full maternal isodisomy for chromosome 7 (upid(7)mat) in this patient. Furthermore, since such a condition is frequently associated with mosaicism for trisomy 7 [Petit et al, 2011], we performed fluorescence in situ hybridization (FISH) analysis for stocked lymphocyte pellets, using a CEP7 probe for D7Z1 (Abbott Laboratories, Abbott Park, IL). The FISH analysis identified two normal signals in 995 of 1,000 interphase nuclei examined, with no trace of trisomic nuclei; while a single signal was delineated in the remaining five nuclei, this was regarded as a false‐positive finding.…”

“…However, the presence or absence of demonstrable trisomic cells was studied only in lymphocytes. In this regard, trisomic cells have been identified more frequently in skin fibroblasts and amniocytes than in blood cells in patients with mosaic trisomy 7 [Chen et al, 2010; Petit et al, 2011], and they are usually more frequently detected in the placental tissue than in the body tissue, as has been demonstrated by confined placental trisomy [Kalousek et al, 1991]. These findings would argue for the possible presence of trisomic cells in several tissues including placenta of this patient.…”

Formation of upd(7)mat by trisomic rescue: SNP array typing provides new insights in chromosomal nondisjunction

“…Interestingly, we did not get any evidence for trisomy 7 mosaicism in three hUPD carriers, although the upd(7)mat formation by trisomic rescue has been proven directly or indirectly in single studies [6, 7, 12, 20, 21]. In fact, low-level mosaicism can hardly be detected by SNP array analysis, but we think that trisomy 7 cell lines should be extremely rare in the body as this constitution is not compatible with life.…”

Do you know this syndrome? Dyspigmentation along the Blaschko lines caused by trisomy 7 mosaicism

“…4 Extracutaneous findings in trisomy 7 mosaicism included renal malformation, facial dysmorphism and growth retardation without a typical clinical presentation. In our case, additional findings of hypertrichosis, musculoskeletal and minor neurodevelopment abnormalities were evident.…”