Severe Phenotype in a Girl with Partial Tetrasomy 7, Karyotype 46,XX,trp(7)(q35q36)

Abstract

On prenatal ultrasonography, polyhydramnion, internal hydrocephalus, hypoplasia of the corpus callosum, and dysmorphic features were detected in a fetus of a 22-year-old mother. Subsequent karyotyping of amniocytes revealed supernumerary material in distal 7q. The baby was delivered after 38+4 weeks of gestation, and postnatal array CGH analysis showed a triplication of 7q35→q36, resulting in partial tetrasomy. The triplication was not distinguishable from a duplication by conventional and molecular cytogenetic methods, but was clearly identified by array CGH analysis. The phenotype was rather severe with limited cardiac contractility and subsequent respiratory problems, as well as progressive neurologic deterioration and several dysmorphic features. Triplications in general are rare, and this case is the first report of a microscopically visible triplication in 7q. Duplication patients of the same chromosomal segment also showed a severe phenotype, however, in our opinion there are no common features suggesting a clinically recognizable distal 7q duplication/triplication syndrome.

Genomic characterization of prenatally detected chromosomal structural abnormalities using oligonucleotide array comparative genomic hybridization

“…Developmental delay and postnatal overgrowth might be suspected in case 2 because the 18.6 Mb supernumerary marker derived from chromosome 4 resulted in a partial segmental trisomy of over 65 genes including the IGFBP7 gene. The infant in our case has not shown any abnormality at age 1 year; and the trisomy segment is smaller than that reported by Bonnet et al For case 3, the compound effect from the 24.9 Mb deletion of 5p encompassing critical regions of speech delay, cat-like cry, MR, and facial dysmorphism of Cri du Chat syndrome [Zhang et al, 2005] and the 13.3 Mb 7q duplication [Lehnen et al, 2009] predicts a severe phenotype. The 6q27 deletion in case 4 includes the smallest deleted region and the proposed candidate gene TBP for MR [Rooms et al, 2006].…”

“…Case-oriented prenatal and follow-up postnatal genomic analyses have been used to further delineate prenatally detected chromosomal abnormalities [Baldwin et al, 2008; Lehnen et al, 2009; Rossi et al, 2009]. As demonstrated in this report, further characterization of gene copy number aberrations as opposed to chromosomal G-band abnormalities provides better predictive insight and, in turn, better patient management.…”

Low-copy repeats at the human VIPR2 gene predispose to recurrent and nonrecurrent rearrangements

“…Bartsch et al 20 described independent small (550 kb) 7q36.3 microduplication and atypical 17q11.2 (NF1) microdeletion in a girl with neurofibromatosis and concluded that the 7q36.3 trisomy represented a subtelomeric CNV without phenotypic consequences. Lehnen et al 21 reported a severe phenotype in a girl with partial tetrasomy 7q35-q36. The only 7q36 duplication reported in the Decipher database (patient 254265, http://decipher.sanger.ac.uk/) in a subject with developmental delay, prominent eyes and short stature was inherited from her normal parents.…”

Prenatal diagnosis and molecular cytogenetic characterization of fetuses with central nervous system anomalies using chromosomal microarray analysis: a seven-year single-center retrospective study

“…Partial trisomy 7q32.1q36.3 and 10q26.2q26.3 microdeletions were observed in Case 2 with the isolated ultrasound anomaly of hydrocephalus. Existing studies have suggested that partial trisomy or tetrasomy 7q may result in hydrocephalus 20 , 21 . Thus, we believe that the 7q32.1q36.3 duplication in this case may be the prime reason for the clinical feature of fetal hydrocephalus.…”