The association of congenital skin disorders with acetylcholinesterase in amniotic fluid

We describe a fetus with epidermolysis bullosa dystrophica and a fetus with aplasia cutis congenita who were normal by careful ultrasound examination but whose midtrimester amniotic fluids exhibited elevated concentrations of alpha-fetoprotein and presence of acetyl-cholinesterase. These cases show that serious fetal skin pathology can be a source of amniotic fluid acetylcholinesterase and elevated alpha-fetoprotein concentration and should be considered as part of the differential diagnosis of these amniotic fluid findings.     

False-negative amniotic fluid acetylcholinesterase in a case of meningo-encephalocele

We describe a patient with a significantly elevated serum alphafetoprotein (AFP) concentration at 17 weeks of gestation, who showed only a marginally increased amniotic fluid AFP and lacked the second rapidly migrating band of acetylcholinesterase electrophoresis. Ultrasound examination revealed an encephalocele and ventriculomegaly. Autopsy showed that the encephalocele was not covered by skin.     

Accuracy of amniotic fluid testing before 21 weeks' gestation in prenatal diagnosis of congenital cytomegalovirus infection

Cytomegalovirus (CMV) is the most common cause of intrauterine infection. Recent publications show amniocentesis to have an 81–100 per cent sensitivity in antenatal diagnosis after 21 weeks' gestation. Testing before 21 weeks' gestation is less well documented. We performed 36 amniocenteses between 14 and 20 weeks' gestation. The sensitivity was 45 per cent and the specificity 100 per cent. Implications and possible causes of this low sensitivity are discussed.     

Appearance of excessive lipids in amniotic fluid as a sign of fetal hyperlipidaemia

The appearance of excessive lipids in amniotic fluid during Caesarean section raised the suspicion of a hyperlipidaemic fetus. The amniotic fluid had elevated cholesterol (53 mg/dl) and triglycerides (81 mg/dl). At the age of 2 months, the infant was hyperlipidaemic (cholesterol of 161 mg/dl and triglycerides of 84 mg/dl). The case suggests the possibility of prenatal diagnosis of hyperlipidaemia, a major risk factor for atherosclerosis.     

Prenatal diagnosis and treatment of fetal long QT syndrome: a case report

We report a case of a fetus presenting with bradycardia, intermittent atrioventricular (AV) block, ventricular tachycardia (VT) and the signs of fetal congestive heart failure (ascites and scrotal hydrocele) during mid-gestation. Prenatal treatment with β-adrenergic blocker (propranolol) and digitalis glycosides was prescribed because of suspicion of long QT syndrome occurring with fetal congestive heart failure. The male baby was born at 39 weeks of gestation and showed a prolonged QT interval (QTc = 492 ms) and frequent variable AV block or alternating left and right bundle branch block, depending on the atrial rate. Prenatal administration of lidocaine failed to correct the fetal VT. Conversely, propranolol decreased the attack frequency of fetal VT. Postnatal administration of the K⁺ channel opener (nicorandil) successfully shortened the QT interval and improved the outcome. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of the fragile X syndrome using fetal blood and amniotic fluid

Nineteen pregnancies at risk for the Martin–Bell syndrome have been monitored during the second trimester for the presence of the fragile Xq27. Of the 19 potential carrier mothers, 14 showed the presence of the fragile X in their lymphocytes at a level of 4 per cent or above. As one was a twin pregnancy, fetal blood was obtained at fetoscopy from 20 fetuses and amniotic fluid obtained simultaneously from 19 of them. Of the 20 fetuses, 18 were males (including both of the twins) and two were females. Of these 18 males, seven were found to carry the fragile Xq27 in lymphocytes and subsequently six of the seven were terminated. The diagnosis was confirmed in five of the six terminated fetuses (the sixth case was a patient whose pregnancy was terminated abroad) and also in a full-term male baby. Five of the seven males without the marker X who came to term had their karyotypes confirmed post natally. Of the two female fetuses one was found to be a carrier of the fragile X and the other was not. Both babies had full-term deliveries and both had their karyotypes confirmed post natally. In some cases the diagnosis made in fetal lymphocytes was confirmed later in amniocytes.     

Role of amniotic fluid interphase fluorescence in situ hybridization (FISH) analysis in patient management

We retrospectively reviewed 309 amniotic fluid interphase fluorescence in situ hybridization (FISH) analyses performed from October 1995 to June 1999 to assess the role of interphase FISH in the management of patients at increased risk for fetal aneuploidies. Gestational age and indications for amniocentesis, clinical interventions after FISH results, as well as interventions after final culture reports were analyzed. There were 244 (79%) normal, 50 (16%) abnormal and 15 (5%) inconclusive FISH results. There were no false-positive or false-negative results, but there were nine (3%) clinically significant chromosomal abnormalities not detectable by FISH. Of the 50 women with abnormal FISH results, 26 (52%) elected to terminate the pregnancy prior to the availability of the standard chromosome analysis. In two of the fetuses with trisomy 21 no abnormalities were reported by ultrasound examination. Our experience indicates that interphase FISH results played an important role in decision making, especially for pregnancies close to 24 weeks' gestation. Standard karyotype analysis is still required for detection of chromosome abnormalities not detectable by interphase FISH techniques and for clarification of unusual or inconclusive FISH results. Copyright © 2001 John Wiley & Sons, Ltd.     

Mild fetal cerebral ventriculomegaly as a prenatal sonographic marker for Kartagener syndrome

Primary ciliary dyskinesia (PCD), also referred to as immotile-cilia syndrome or Kartagener syndrome, is a group of genetic disorders caused by defective cilia leading to chronic sinupulmonary infection, situs inversus and reduced fertility. Some PCD patients also have cerebral ventriculomegaly or hydrocephalus. We report here two fetuses and one newborn with mild cerebral ventriculomegaly and a suspected and/or confirmed diagnosis of PCD. These cases demonstrate that mild fetal cerebral ventriculomegaly can be a prenatal sonographic marker of PCD, certainly in fetuses with situs inversus or a history of a previous sib with PCD. Copyright © 2003 John Wiley & Sons, Ltd.     

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.     

Prenatal diagnosis of Joubert syndrome: a case report

Joubert syndrome is a rare, autosomal recessive condition, first described by Joubert in 1969. We present a case of Joubert syndrome from a consanguineous family in which, apart from the cerebellar vermis agenesis, ventriculomegaly, bilateral postaxial polydactyly of hands and right foot and micropenis, episodes of fetal breathing pattern with an increased respiratory rate were also demonstrated by prenatal ultrasound scan. At birth the infant showed an odd face and bilateral fleshy nodules of the tongue. He had an abnormal breathing pattern of alternating tachypnea and apnea. Cranial MRI showed molar tooth sign, hydrocephalus and Dandy–Walker malformation. He had nystagmus, and electroretinography showed retinal dystrophy. Copyright © 2002 John Wiley & Sons, Ltd.