Mid-trimester fetal sex determination from maternal peripheral blood by fluorescence in situ hybridization without enrichment of fetal cells

To determine the fetal sex on 30 women who were 16–20 weeks pregnant, about 100 000 maternal blood nucleated cells were analysed by means of fluorescence in situ hybridization (FISH) with a Y-chromosome-specific DNA probe. Cells with the hybridization signal were detected in 12 of the 30 women. All the 12 mothers gave birth to a male child. Of the other 18 women who had no Y-positive cells in the peripheral blood, 14 gave birth to a female child and four gave birth to a male child. These false-negative results probably occurred because the number of cells examined was inadequate. The data obtained in this study suggest that fetal sex determination using maternal peripheral blood with FISH is possible and that this diagnostic method will be clinically useful when more cells are analysed.     

Cytogenetic abnormalities among perinatal deaths demonstrating a single umbilical artery

The presence of a single umbilical artery is associated with fetal congenital malformations and cytogenetic abnormalities. The incidence of chromosomal abnormalities in perinatal deaths complicated by a single umbilical artery is unknown. We studied the proportion of cytogenetic abnormalities associated with a single umbilical artery among perinatal deaths undergoing autopsy. Of 1078 autopsies, 42 (3·9 per cent) were identified with a single umbilical artery. Chromosome analysis was attempted in 21 of the 42 cases (50 per cent). There were 16 successful chromosome analyses, of which three (18·75 per cent) were abnormal. All the chromosomally abnormal fetuses had major congenital malformations. These data suggest that in a perinatal death, the presence of a single umbilical artery does not clinically alter the a priori risk of cytogenetic abnormalities.     

Prenatal diagnosis of tyrosinase-negative oculocutaneous albinism by an electron microscopic dopa reaction test of fetal skin

An electron microscopic DOPA reaction test of fetal skin was used for the prenatal diagnosis of tyrosinase-negative oculocutaneous albinism (OCA). The subject was a 34-year-old Japanese woman in her second pregnancy. Her first child, born in 1982, had been previously examined and confirmed to have tyrosinase-negative OCA. The parents requested a prenatal diagnosis and we sampled skin from the upper trunk of the fetus. On conventional electron microscopy, the development of melanosomes in interfollicular melanocytes had progressed no further than stage II. Fetal skin samples incubated with L-DOPA solution indicated a lack of tyrosinase activity and showed that the melanosomes had not progressed beyond stage II. In skin samples from the trunks of three Japanese fetuses aborted for other reasons at 19–20 weeks of gestation, most premature melanosomes were further melanized to stage IV after incubation with L-DOPA solution. A prenatal diagnosis of tyrosinase-negative OCA was made. The parents requested a termination and skin biopsies of the abortus confirmed the diagnosis. This study shows that tyrosinase is normally present in melanocytes of the fetal epidermis at 20 weeks' gestation, and that the electron microscopic DOPA reaction test of a fetal skin biopsy specimen is safe and practical, and provides reliable information for making a prenatal diagnosis of tyrosinase-negative OCA in the second trimester.     

Ultrasound observation of amnion dysmorphism at 14.5–16 weeks

The presence of chorio-amniotic separation and amnion anomalies was recorded in 9500 patients referred for vaginal ultrasound examination at 14.5–16 weeks' gestation. In all patients with a change in the amnion, a search for fetal anomalies was performed and pregnancy outcome was checked. Amnion dysmorphism was observed in 30 cases. The main findings were a floating membrane which changed its configuration when the uterus was tilted and multiple intrauterine amniotic sheets. In no case was attachment of the fetus to the membranes noted. There was no fetal abnormality and pregnancy outcome was favourable in all patients. In conclusion, ultrasound visualization of amnion dysmorphism in early pregnancy is not associated with an adverse pregnancy outcome.     

Prenatal diagnosis of recurrent Larsen syndrome: Further definition of a lethal variant

Larsen syndrome is characterized by multiple congenital joint dislocations and flattened facies. Some cases have been familial, with both autosomal dominant and recessive patterns of inheritance. Reports of a form of Larsen syndrome, lethal in the neonatal period, are reviewed. We present a family in which recurrence of the syndrome was diagnosed prenatally, but a lethal outcome again resulted despite preparation for anticipated perinatal complications. Because of the wide clinical variation and the lack of a known metabolic defect, delineation between the various forms of Larsen syndrome is difficult. While the lethal variant appears to be a combination of the Larsen phenotype and pulmonary hypoplasia, other features noted in the lethal cases, such as abnormal palmar creases and laryngotracheomalacia, are also seen in patients with Larsen syndrome who survive.     

Prenatal diagnosis of anhidrotic ectodermal dysplasia

This paper reports on successful prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia (AED) by means of light and electron microscopy on fetal skin biopsies obtained under fetoscopy. In the present family two brothers of the proband were severely affected with the full symptomatology of AED, the pregnant female and her mother revealed minor symptoms with patches of skin lacking vellus hair. Control of lesional skin of the affected family members by electron microscopy revealed no ultrastructural abnormalities. However, all biopsies lacked skin appendages including hair follicles, sebaceous glands, and sweat glands. The lack of pilosebaceous follicles can be used as a diagnostic criterion since these structures are fully developed in normal fetuses of 20 weeks whereas the development of sweat glands does not start before week 20 to 24 of fetal life. Skin biopsies were taken from various regions of the fetus at risk via fetoscopy in week 20 and processed for light and electron microscopy. All samples revealed complete absence of all skin appendages in contrast to a total of 61 non-AED fetuses. Thus positive prenatal diagnosis of AED was made and the pregnancy was terminated. Control investigations after abortion confirmed the diagnosis.     

Harlequin fetus and micromelia

A fetus was born prematurely after a 34-week pregnancy whose evolution was marked by the ultrasonic finding at 23 weeks of a considerable shortening of the long bones. At birth, the newborn infant bore the appearance of a harlequin fetus. There was no dwarfism, but the micromelia discovered in utero was confirmed both clinically and radiologically. Such global micromelia associated with this kind of pathology has never been described, not to mention witnessed, in utero and may be part of the fetal akinesia sequence phenotype.     

Prenatal diagnosis of distal arthrogryposis type I by ultrasonography

Two consecutive pregnancies in a woman with initially undiagnosed type I distal arthrogryposis (DA) are reported. A prenatal diagnosis of the condition was made by ultrasound in the 17th week of gestation in one of the pregnancies, whereas in the subsequent pregnancy the disorder was excluded as early as 13 weeks' gestation. The diagnoses were verified at birth. The feasibility of prenatal diagnosis of DA type I in the second trimester is thus confirmed and its possibility in the late first trimester is suggested.     

Atelosteogenesis type II: Sonographic and radiological correlation

Atelosteogenesis type II is a lethal chondrodysplasia characterized by severe micromelia, spinal abnormalities, talipes equinovarus, and abducted thumbs and toes. We present a case diagnosed at 21 weeks of gestation in which antenatal sonographic and post-mortem radiological findings were correlated. The patient had a recurrence of this disorder in a subsequent pregnancy which was terminated at 15 weeks, supporting previous reports of an autosomal recessive inheritance pattern. The feasibility of diagnosing the following morphological features by prenatal ultrasonography is demonstrated: coronal clefts of the vertebral bodies, metaphyseal and epiphyseal abnormalities, spinal deviations such as cervical kyphosis and a horizontal sacrum, additional ossification centres in the pelvis, and preaxial deviation of the thumbs and toes. The differential diagnosis of this disorder from other skeletal dysplasias with similar features is discussed.