Del (18p) syndrome with increased nuchal translucency revealed in prenatal diagnosis.

Abstract

Fetal chromosomal abnormality and increased nuchal translucency (INT) association is well established (6). There are several reports about the association between foetal chromosomal abnormalities including triploidy, trisomies 13, 18, 22, tetrasomy 12p and increased nuchal translucency (INT) during the first trimester of pregnancy (6). More than 70% of cases with trisomy 21 can be detected by screening for INT (8). In the present foetus with monosomy 18p, we observed INT as the only abnormal ultrasonographic finding during pregnancy. Amniocentesis was performed at 18 weeks of gestation on a 41 years old Turkish female referred for prenatal diagnosis because of advanced maternal age. INT was observed at the time of amniocentesis (2.8 cm). The couple had a healthy four year-old girl with 46,XX karyotype. Conventional cytogenetic analysis of cultured amniocytes showed an unbalanced whole arm translocation between the long arm of one chromosome 18 and the long arm of one chromosome 22, 45,XX, der(18)t(18;22)(ql0;ql0), which led to monosomy 18p in the foetus (Fig. Ia). Parental karyotypes were normal, thus the aberration had occurred de novo. The derivative chromosome had one centromere revealed by conventional C banding staining. Whether the centromere originated from chromosome 18 or chromosome 22 could not be determined by FISH. Chromosome 18p STS markers D18S498, D18S481 and D 18Sl 70 were used for genotyping of the foetus and parents, to determine the origin of derivative chromosome 18. Marker D 18Sl 70 was informative: while her parents were heterozygous for this marker, the foetus had only the paternal allele, thus the maternal chromosome 18 was found to be involved in the translocation (Fig. Ib). The parents decided to terminate the pregnancy at 21 weeks of gestation based on the chromosomal abnormality. At autopsy, 362.62 g weight of foetus, supraorbital flatness, depressed nasal bridge, flared nostrils and low set ears were observed. Placenta weight was lower (170 g) than average (normal range relative to 21 weeks of gestation is 180 g) (1). Deletion of the short arm of chromosome 18, the del(18p) syndrome, is the second most frequent autosomal deletion syndromes. Since the del(18p) syndrome was first described by de Grouchy et al. (2), more than 150 cases have been reported. Most cases appear as a result of de now terminal deletions (85%) or ring chromosomes, and about 15% of del(18p) originate from unbalanced translocations between the long arms of chromosome 18 and acrocentric chromosomes, predominantly chromosomes 14, 21 or 22 (7). Clinical manifestations of monosomy 18p varies widely (3), but usually comprises mental and growth retardation, craniofacial dysmorphism including round face, dysplastic ears, wide mouth, and dental anomalies. Cardiac defects and genital anomalies, and even prenatally detected holoprosencephaly have also been reported (5, 9, 10). Variable phenotypes are related to del(18p) syndrome, which makes the prenatal diagnosis and genetic counseling of the cases with 18p monosomy difficult (7). In the detailed autopsy analyses of our case performed following termination of the pregnancy, corpus callosum agenesis, holoprosencephaly, hydrocephaly, cardiac defects and genital abnormalities, which are among malformations specific for del(l 8p) syndrome, were not observed. Supraorbital flatness, depressed nasal bridge, flared nostrils and low set ears were observed as dysmorphic findings, however, confident determination in fetuses is difficult. …