Prenatal diagnosis of tetrasomy 9p
To the Editor:
Dhandha et al. [2002] report three cases of tetrasomy 9p and provide a useful and interesting case review from the literature. Tetrasomy 9p is a rare clinical syndrome with only 32 cases reported to date, with reports of both mosaic and non-mosaic cases. The phenotypic differences of tetrasomy 9p seem to be the result of the degree of mosaicism. We recently identified a patient with tetrasomy 9p diagnosed prenatally and report our findings here.
The mother was a 22-year-old gravida 1 para 0 white woman. During the pregnancy, multiple fetal anomalies were identified by repeated ultrasounds, as early as 22 weeks of gestation. These fetal anomalies included a strawberry shaped skull, mildly enlarged fetal ventricles, bilateral cleft lip and palate, a small-sized stomach, a possible horseshoe kidney, and rockerbottom deformity of the foot and/or clubfeet. Also noted was persistent abnormal posturing of the fetal fists with overlapping of the fetal digits. Amniocentesis was performed at 24 weeks of gestation, which showed 47,XX,+i(9)(p10) in 20 cells. The isochromosome was confirmed as chromosome 9 by FISH.
The patient was born by induced labor at 35 5/7-week gestation due to premature rupture of membranes. The infant was a female weighing 1,730 g, 41 cm long, with occipital frontal circumference (OFC) of 28.5 cm at birth. Apgar scores were 1 and 6 at 1 and 5 min, respectively. Physical examination at birth revealed strawberry-shaped head, downslanting palpebral fissures, large anterior fontanel, hypertelorism, bilateral small low-set ears, micrognathia, beaked nose, bilateral cleft lip and cleft palate, brachydactyly with hypoplastic thumb, and bilateral foot deformities with eversion. The patient was also found to have patent foramen ovale, bicuspid aortic valve, and patent ductus arteriosus. At 33 days of age, the patient died of aspiration pneumonitis with respiratory distress.
Ultrasound and MRI of the head were performed postnatally, and diagnoses of hydrocephalus, ventriculomegaly with left ventricle being larger in size than the right one, agenesis of the corpus callosum, and Dandy–Walker variant were made. The above physical findings, along with ventriculomegaly, Dandy–Walker variant, and horseshoe kidney detected by ultrasound, are consistent with the emerging phenotype for tetrasomy 9p, summarized by Dhandha et al. [2002]. Karyotyping from amniocentesis confirmed our case as tetrasomy 9p. Chromosomal analysis was also performed on peripheral blood lymphocytes and cord fibroblasts of the infant at birth. All but one of the 20 cells from lymphocytes, and all but three of the 20 cells from fibroblasts, showed identical karyotype as her amniocytes, 47,XX,+i(9)(p10). The one cell from lymphocytes and three cells from fibroblasts analyzed showed a normal female karyotype, suggesting low level of mosaicism. In our patient, we were able to analyze three different tissues, and found low level of mosaicism in two of the three cell types. No early deaths are reported for mosaic cases of tetrasomy 9p. The level of mosaicism seen in our case at birth was very low. Considering that all of her amniocytes analyzed had an abnormal karyotype, this could represent a non-mosaic case of tetrasomy 9p in the fetus, and thus account for the early death in our patient.
