Tetrasomy of the short arm of chromosome 9: Prenatal diagnosis and further delineation of the phenotype

Abstract

A fetus with multiple malformations was identified by prenatal ultrasound investigation. Cordocentesis and fetal lymphocyte chromosome analysis demonstrated a model number of 47 chromosomes. The extra chromosome material was identified as an isochromosome of the entire short arm of chromosome 9 with no involvement of the heterochromatic region of the long arm [47,XY, + i(9p)]. This represents the first report of prenatal diagnosis of tetrasomy 9p. Further delineation of the phenotype is discussed.

Three cases of tetrasomy 9p

“…Reports of tetrasomy 9p in the literature can be grouped into three types based on the nature of the isochromosome. There have been 12 cases [Rutten et al, 1974;Orye et al, 1975;Moedjono et al, 1980;Cuoco et al, 1982;Garcia-Cruz et al, 1982;McDowall et al, 1989;Schaefer et al, 1991;Van Hove et al, 1994;Leichtman et al, 1996;Dutley et al (2 cases), 1998;Eggermann et al, 1998] reported in which the isochromosome has breakpoint at p10, with no portion of the long arm of chromosome 9 present. In nine cases [Balestrazzi et al, 1983;Cavalcanti et al, 1987;Papenhausen et al, 1990;Melaragno et al, 1992;Grass et al, 1993;Park et al, 1995;Tonk, 1997;Dutley et al, 1998;Stumm et al, 1999], the isochromosome included a small amount of the heterochromatic region of 9q, extending to 9q12 or 9q13.…”

Tetrasomy 9p due to an intrachromosomal triplication of 9p13-p22

“…Frequently described major congenital anomalies in these patients are urogenital anomalies (e.g., small penis and cryptorchid testis), skeletal anomalies (e.g., joint dislocation, clubfeet, and kyphosis), cleft lip/palate, and cardiac anomalies (ASD and VSD) [Grass et al, 1993;Schinzel, 1994]. In Table I we summarized major abnormalities and facial anomalies of 10 cases of nonmosaic tetrasomy 9p caused by the presence of an isochromosome 9p (only isochromosomes consisting of 9p material or 9p with heterochromatic material of 9q) [Moedjono et al, 1980;Garcia Cruz et al, 1982;Foerster et al, 1985;Cavalcanti et al, 1987;McDowall et al, 1989;Jalal et al, 1991;Schaefer et al, 1991;Van Hove et al, 1994;Park et al, 1995;Leichtman et al, 1996] and compared them with our case. As expected, similarities exist between our patient and previously reported tetrasomy 9p patients (including psychomotor retardation, hydrocephalus, large fontanels, hypotonia, and similar facial anomalies).…”

Tetrasomy 9p Mosaicism Associated with a Normal Phenotype

“…Prenatal diagnosis of tetrasomy 9p, both mosaic and nonmosaic, has been reported previously [3,18,19] . In one report, two cases were diagnosed prenatally by amniocentesis following abnormal ultrasound appearances [3] and another by cordocentesis following an abnormal prenatal ultrasound [19] .…”

“…In one report, two cases were diagnosed prenatally by amniocentesis following abnormal ultrasound appearances [3] and another by cordocentesis following an abnormal prenatal ultrasound [19] . However, as expected by the documented lower frequency of abnormal cells in fi broblasts typical of tetrasomy 9p, a further case showed a normal karyotype in amniocytes tested due to advanced maternal age.…”