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.     

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.     

Transvaginal chorionic villus sampling using transabdominal ultrasound guidance

Transvaginal chorionic villus sampling (CVS) using concurrent transabdominal ultrasound guidance was performed in six women who desired CVS but could not be offered transcervical or transabdominal approaches because of uterine position and placental location. Satisfactory amounts of chorionic villi were obtained in all six cases with no maternal discomfort, an occurrence that contrasts with our experience in transvaginal CVS using endovaginal ultrasound guidance. We believe that transvaginal CVS using concurrent transabdominal ultrasound guidance warrants consideration as an alternative technique for first-trimester CVS in selected patients.     

Prenatal diagnosis of autosomal dominant polycystic kidney disease using flanking DNA markers and the polymerase chain reaction

A prenatal diagnosis was carried out on a 9-week-old fetus at risk for autosomal dominant polycystic kidney disease (ADPKD). Ten members of the family were previously typed using five DNA markers linked to the PKD1 locus on chromosome 16, and one marker linked to the putative PKD2 locus on chromosome 2. The polymerase chain reaction (PCR) was used to amplify the D16S125 locus. Pairwise and multipoint lod scores indicated that the family was most likely segregating a PKD1 mutation. The fetus inherited the disease haplotype from the affected parent. Diagnostic accuracy was greater than 99 per cent, taking into account the possibility of genetic heterogeneity.     

Sonographically determined anomalies and outcome in 170 chromosomally abnormal fetuses

Structural pathology and outcome were studied in 170 chromosomally abnormal fetuses. Numerical chromosomal abnormalities were established in 158 (93 per cent) cases, of which 110 (71 per cent) represented trisomies, 30 (18 per cent) Turner syndrome, and 18 (11 per cent) triploidy. Structural chromosomal abnormalities were diagnosed in 12 (7 per cent) cases. Gestational age at referral was significantly shorter for pregnancies with Turner syndrome than for the other chromosomal abnormalities. Referral before 20 weeks of gestation was mainly based on fetal structural pathology alone (92 per cent); after 20 weeks, patients were referred because of structural pathology combined with small for gestational age, oligohydramnios, or polyhydramnios. Referral as a result of suspected multiple organ pathology occurred in 73.5 per cent of pregnancies. An abnormal amniotic fluid volume was present in 59/170 (34.5 per cent) chromosomally affected pregnancies, i.e., oligohydramnios in 31 and polyhydramnios in 28 cases. Birth weight was below the tenth percentile in over half of the chromosomally abnormal fetuses, except for Turnersyndrome. Fetal outcome was poor, with a survival rate at 1 month of 30 per cent for trisomies which was mainly determined by trisomy 21 (14/18=77.5 per cent).