Congenital limb deficiencies in newborn infants: prevalence,characteristics and prenatal diagnosis

Congenital limb deficiency (CLD) occurs in 0.54 to 0.59/1000 live-born infants and varies according to its anatomic location, type and cause. Our aim was to present a fetus with a prenatal ultrasonographic diagnosis of CLD (transverse reduction deficiency of the left upper limb), and to determine the prevalence and clinical characteristics of CLD at a tertiary medical centre in Israel. Among 78 500 live-born infants, there were 24 cases of CLD (0.31/1000): 45.8% of the CLD cases with affected upper limbs, 45.8% with affected lower limbs, and 8.4% with both limbs affected; 88.4% of the limb deficiencies were longitudinal and 11.6% were transverse; and, 33.3% (8/24) of the affected newborn infants had additional congenital anomalies. We conclude that CLD is not an infrequent finding in live-born infants. Comprehensive ultrasonography of the fetus allows early prenatal diagnosis of CLD and provides the parents with important information and helps them in their decision regarding the fate of the pregnancy. Copyright © 2003 John Wiley & Sons, Ltd.     

Preimplantation genetic diagnosis for familial amyloidotic polyneuropathy (FAP)

Preimplantation genetic diagnosis (PGD) was developed more than a decade ago to offer an alternative to prenatal diagnosis for couples at risk of transmitting an inherited disease to their offspring. Portuguese-type familial amyloidotic polyneuropathy (FAP type I), is an autosomal dominant disease presenting an inherited mutation in the gene encoding the plasma protein transthyretin (TTR). We here report the first protocol for single-cell detection of the Met30 mutation in FAP type I and its application to PGD. A nested PCR reaction for exon 2 of the TTR gene was developed. The PCR product was then analysed by restriction enzyme analysis and SSCP allowing the detection of the point mutation. Ten clinical cycles were performed in seven couples. From the 93 metaphase II (MII) injected oocytes, 82 were normally fertilized and 78 were biopsied. A positive signal in the nested PCR reaction was obtained in 61 blastomeres, corresponding to a DNA amplification efficiency of 78.2%. No allele dropout (ADO) or contamination were detected. A biochemical pregnancy was obtained in three cases and a clinical pregnancy in one couple is actually in normal evolution. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of complete sole trisomy 1q

The prenatal diagnosis of a complete trisomy of the long arm of chromosome 1 is reported. Major ultrasound findings included: nuchal thickening, bi-temporal narrowing, a single choroid plexus cyst, andmild ventriculomegaly. There was a mass in the chest and abdomen, pleural effusion, ascites and a hyperechoic bowel. Skin edema was present. The fetus died at 26 weeks' gestation. A literature review is presented of 17 de novo and two inherited cases with only trisomy 1q. Of note is the fact that 3/5 prenatally detected 1q trisomies have teratomas. A review of the literature reveals a dismal outcome fortrisomy 1q cases if the duplication involves bands 1q25→q32. Copyright © 2001 John Wiley & Sons, Ltd.     

Cryptic 1p36.3/6q25.2 translocation in three generations ascertained through a foetus with IUGR and cerebral malformations

Here we describe a foetus with intrauterine growth retardation (IUGR), cerebral malformations and a 46,XY,der(1),t(1;6)(p36.3;q25.2) karyotype owing to a familial cryptic translocation segregating in three generations. A balanced translocation was present in the mother, the maternal uncle, the aunt and the grandmother. A female first cousin with dysmorphisms, hydrocephalus and mental retardation was a carrier of a partial trisomy 1p and a partial monosomy 6q. Multiple miscarriages were present in the family pedigree. Parents of the foetus had three other pregnancies: a male with a balanced translocation, and two foetuses with 1p36.3–pter monosomy and 6q25.2–qter trisomy. Copyright © 2003 John Wiley & Sons, Ltd.     

Residual risk for cytogenetic abnormalities after prenatal diagnosis by interphase fluorescence in situ hybridization (FISH)

Results from conventional cytogenetic studies on 21 609 amniotic fluid specimens were analyzed retrospectively to determine the residual risk for a cytogenetic abnormality if interphase FISH, capable of only detecting aneuploidy for chromosomes 13, 18, 21, X and Y, was performed and did not reveal an abnormality. Detection rates (the probability of detecting a cytogenetic abnormality when an abnormality is present) and residual risks (the likelihood of a cytogenetic abnormality, in view of normal interphase FISH results) were calculated for the four major clinical indications for prenatal diagnosis (advanced maternal age, abnormal maternal serum screen indicating increased risk for trisomy 18 or trisomy 21, abnormal maternal serum screen indicating increased risk for neural tube defects and ultrasound abnormality). Differences in detection rates were observed to depend on clinical indication and presence or absence of ultrasound abnormalities. The detection rate ranged from 18.2 to 82.6% depending on the clinical indication. The detection rates of abnormalities significant to the pregnancy being evaluated (i.e. abnormalities excluding familial balanced rearrangements and familial markers) were between 28.6 and 86.4%. The presence of ultrasound abnormalities increased the detection rate from 72.2 to 92.5% for advanced maternal age and from 78.6 to 91.3% for abnormal maternal serum screen, indicating increased risk for trisomy 18 or trisomy 21. With regard to residual risk, the risk for a clinically significant abnormality decreased from 0.9–10.1%, prior to the interphase FISH assay, to a residual risk of 0.6–1.5% following a normal interphase FISH result in the 4 groups studied. Providing patients with detection rates and residual risks, most relevant to their situation (clinical indication and presence or absence of ultrasound abnormality) during counseling, could help them better understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation. Copyright © 2003 John Wiley & Sons, Ltd.     

Direct fetal chromosome studies from chorionic villi

An easy and reproducible technique for direct fetal chromosome analysis after chorionic biopsy is described. Very high colchicine concentration and rehydratation of the fixed villi are the two original points of this method.