Phenotypical variation in cousins with the identical partial trisomy 9 (pter‐q22.2) and 7 (q35‐qter) at 16 and 23 weeks gestation

Abstract

From the study of numerical and structural chromosomal abnormalities, there is convincing evidence and accumulating information of a direct karyotype to phenotype correlation. Knowledge of phenotypic consequences of a specific chromosomal imbalance is important for genetic counseling and prenatal diagnosis. However, for unbalanced non-Robertsonian translocations a precise karyotype to phenotype correlation is difficult to predict for several reasons: (I) unbalanced non-Robertsonian translocations are rare, (II) the published case reports are often not age-matched, (III) varying breakpoints result in different lengths of the monosomic and trisomic segments and therefore the phenotype will depend on additional genes present or the loss of coding regions, and (IV) the combination of the same trisomy with different monosomies, or vice versa, can result in diverging phenotypes. Therefore, the study of the karyotype to phenotype correlation in affected relatives of the same age and the identical unbalanced translocation provides a good model to investigate phenotypic consequences of a specific genetic imbalance. We report of two second trimester fetuses with the identical major partial trisomy 9 (9pter-9q22.2) and minor partial trisomy 7 (q35-qter) resulting from a familial translocation (7;9)(q35;q22.2)mat. One fetus presented with a Dandy-Walker malformation, polymicrogyria, and mild dysmorphic features, whereas the other fetus showed unilateral cleft lip and palate without cerebral anomalies. Potential mechanisms for this different phenotypic expression of the same unbalanced translocation resulting in partial trisomy 9 and 7 in the two cousins and possible consequences for genetic counseling and prenatal diagnosis are discussed.

Dandy–Walker syndrome and chromosomal abnormalities

“…2005) in chromosome 6, and partial trisomy 7q (Chen et al . 1996, 2006; Metzke‐Heidemann et al . 2004) in chromosome 7.…”

“…There have been at least 20 case reports on DWS cases complicated by trisomy 9 (Golden & Schoene 1993). These reports include cases complicated by DWS such as trisomy 9 mosaic syndrome (Bureau et al 1993;Tarani et al 1994;Murru et al 2002), partial trisomy 9 (Zacharias et al 1983;Hannam et al 1999;von Kaisenberg et al 2000;Chen et al 2002aChen et al , 2005Metzke-Heidemann et al 2004), tetrasomy 9p (Melaragno et al 1992;Cazorla et al 2003;Hengstschlager et al 2004), and complete trisomy 9 (McDuffie 1994). The number of these reports shows that DWS can be commonly encountered in chromosome 9.…”

“…There are cases of DWS with complications of trisomy 5p (Kleczkowska et al 1987) and 5p deletion syndrome (Vialard et al 2005) in chromosome 5. There are reports on partial monosomy 6q26 (Weimer et al 2006) and subtelomeric deletions of chromosome 6p (Descipio et al 2005) in chromosome 6, and partial trisomy 7q (Chen et al 1996(Chen et al , 2006Metzke-Heidemann et al 2004) in chromosome 7. There are reports on DWS and partial trisomy 8q (Fan & Siu 2001), and trisomy 8 mosaicism (Nakamura et al 1985) in chromosome 8.…”

Genetics of the polymicrogyria syndromes

“…Potential mechanisms underlying these findings include breakpoint modifications, abnormal imprinting, and interaction with X inactivation, mosaicism, environmental factors, genetic background, and cross regulation. 89 The translocation breakpoints defined in these families may lead to the identification of other genes involved in the development of polymicrogyria.…”

Searching for Genes for Cleft Lip and/or Palate Based on Breakpoint Analysis of a Balanced Translocation t(9;17)(q32;q12)

“…It has been demonstrated that CL/P is associated with trisomy 9q (Metzke-Heidemann et al, 2004), tetrasomy 9q (Wyandt et al, 2000), and chromosomal translocations involving the 9q region: t(6;9)(p23;q22.3) (Donnai et al, 1992); 46,XX,−222,+der(9)t(9;22)(q22;q11.2) (Pivnick et al, 1990); and 46,X,t(X;9)(p22.1;q32) (Zori et al, 1993). Naritomi et al (1989) divided trisomy 9q syndrome into four groups (group 1: trisomy for 9q11>q32, group 2: 9q32>qter, group 3: 9q34, and group 4: 9q13/q21>qter) according to the length of the trisomic segment.…”