Monosomy 21q: two cases of del(21q) and review of the literature

Abstract

We report on two cases of partial monosomy 21 and review cases with a partial or an apparently full monosomy 21. In situ hybridization and/or molecular studies appear to be necessary tools to study imbalance in such a small chromosome and to perform further genotype‐phenotype correlations. The segregation mode in cases with a translocation is adjacent 1, adjacent 2, and 3:1 in about 1/4, 1/4, and 1/2 of the cases, respectively.

Fanconi anemia‐like presentation in an infant with constitutional deletion of 21q including the RUNX1 gene

“…The patient described by Huret had a deletion of 21q21.2-21q22.3 with a partial duplication within 21q22.3 [Huret et al, 1995] that lies entirely within the boundaries of the deletion described in the present patient. This patient had remarkably similar clinical features to ours including intrauterine growth restriction, axial hypotonia with hypertonia of the extremities, facial features including a receding forehead, flat nasal root and broad nose, overlapping fingers, anemia, and thrombocytopenia.…”

“…The platelet abnormalities in many subjects with partial or complete monosomy 21 have demonstrated thrombocytopenia [Abeliovich et al, 1979;Huret et al, 1995;Huret and Leonard, 1997], and recurrent deletion of RUNX1 has emerged in the available case reports of patients with del21q and thrombocytopenia, some of whom also demonstrate qualitative platelet function defects [Shinawi et al, 2008;Katzaki et al, 2010;Lindstrand et al, 2010;Byrd et al, 2011;Thevenon et al, 2011;van der Crabben et al, 2010]. RUNX1 encodes one component of a heterodimeric transcription factor essential for normal hematopoietic development [Okuda et al, 1996;Wang et al, 1996].…”

“…Individuals with partial or complete monosomy for 21q have heterogeneous clinical features that include intrauterine growth restriction, variable cognitive and motor delay, hypertonia, prominent occiput, low hairline, small and downward slanting palpebral fissures, broad nasal root and tip, high arched or cleft palate, microretrognathia, large, low-set ears with prominent antihelices, slender hands with overlapping fingers, and cardiac anomalies [Huret et al, 1995]. The patient described by Huret had a deletion of 21q21.2-21q22.3 with a partial duplication within 21q22.3 [Huret et al, 1995] that lies entirely within the boundaries of the deletion described in the present patient.…”

“…Historically, patients with constitutional deletions of chromosome 21q have been described as having a variety of physical anomalies, birth defects, and developmental and growth delays [Abeliovich et al, 1979;Huret et al, 1995;Huret and Leonard, 1997]. With the availability of chromosomal microarray analysis (CMA), more patients have been identified, and fine mapping of several deletions has revealed the important finding of platelet abnormalities, especially thrombocytopenia, in a number of subjects, with increased risk of developing acute myelogenous leukemia (AML) [Shinawi et al, 2008;Katzaki et al, 2010;Lindstrand et al, 2010].…”

Familial myelodysplastic syndromes: a review of the literature

“…The clinical features of reported cases where descriptions of hematologic findings were available are summarized in Table 2. [28][29][30][31][32][33][34][35][36] All but one case 32 reported thrombocytopenia, with qualitative platelet defects described in 2 cases. 30,36 MDS/AML developed in 3 cases, with a median age of onset of six years (range 5-8 years).…”