Prenatal confirmation of trisomy 12 mosaicism by fetal skin biopsy

Trisomy 12 mosaicism diagnosed at 16 weeks' amniocentesis in a 42-year-old woman was not confirmed at 18 weeks' gestational age in amniotic fluid or fetal blood. Fetal skin biopsy performed at the same time did, however, allow the detection of trisomy 12 in 1 of 14 fibroblasts analysed. Fetal skin biopsy can be included within the diagnostic procedures to be performed when a level III mosaicism is found in the amniotic fluid.     

Prenatal diagnosis of congenital non-bullous ichthyosiform erythroderma (lamellar ichthyosis)

We report the first positive prenatal diagnosis ofcongenital non-bullous ichthyosiform erythroderma or lamellar ichthyosis. Fetal skin samples were obtained by fetoscopy at 21 weeks' gestation and examined by light and electron microscopy. Light microscopy revealed a thickened interfollicular epidermis with multiple layers of flattened cells and excessive keratinization of the epidermal lining of the follicular infundibulum. Electron microscopy of the thickened epidermis revealed granular cells that contained larger-than-normal keratohyalin granules and multiple layers of parakeratotic cornified cells. Although there was regional variation in the degree of interfollicular keratinization, follicles from all regions showed greater and more complete keratinization, indicating that they express the abnormality early enough in development to permit prenatal diagnosis at about 20 weeks' gestation.     

Prenatal diagnosis of carbamoyl-phosphate synthetase deficiency by fetal liver biopsy

In a pregnancy at risk for carbamoyl-phosphate synthetase (CPS) deficiency, prenatal diagnosis was attempted by fetal liver biopsy, performed at 18 weeks of gestation. CPS activity was absent and the diagnosis was confirmed after termination of the pregnancy. The technique employed for fetal liver biopsy is described together with an evaluation of its possible role in prenatal diagnosis.     

Prenatal diagnosis of Harlequin ichthyosis presenting as distal arthrogryposis using three-dimensional ultrasound

We describe a case of Harlequin Icthyosis where the main 2D and 3D ultrasound findings were digital contractures as opposed to the more commonly described severe facial dysmorphisms. A prenatal finding of distal arthrogryposis can therefore include harlequin icthyosis as a differential diagnosis, where 3D ultrasound may then disclose the facial features more commonly associated with the condition. Copyright © 2007 John Wiley & Sons, Ltd.     

Fetal skin biopsy in prenatal diagnosis of some genodermatoses

Various methods of obtaining fetal skin for prenatal diagnosis of certain autosomal-recessive congenital genodermatoses have been assessed. An attempt was made to obtain fetal skin by fetoscopy in 15 patients prior to pregnancy termination for a variety of medical reasons at 18–26 weeks. Specimens were obtained only in five cases (8 successful attempts out of 48). In twelve cases, of which five had a history of a child with junctional (Herlitz type) or dystrophic (Hallopeau-Siemens type) epidermolysis bullosa or non-bullous congenital ichthyosiform erythroderma at 16–25 weeks of pregnancy, fetal skin was obtained without fetoscopy under direct ultrasonic control. Specimens were obtained in all cases (33 successful attempts out of 39). In three cases, fetal pathology was diagnosed by the method of semi-thin and ultra-thin skin sections, and the respective pregnancies were terminated.     

Biochemical examination of fetal skin biopsy specimens obtained by fetoscopy: Use of the method for analysis of keratins and filaggrin

This paper describes a method for biochemical analysis of proteins from fetal skin biopsy samples. The method has wide potential application for diagnosis of disorders with a known protein abnormality detectable by protein staining or a specific antibody. Analysis requires a single 1 mm biopsy, is rapid (2 days) and extremely sensitive. In the present study, fetal skin biopsies from normal fetuses and a fetus at risk for lamellar ichthyosis were obtained. The epidermis or hairs with attached follicular cells were dissected from the remaining skin. Proteins were extracted and separated by SDS-polyacrylamide gel electrophoresis. Proteins from duplicate gels were transferred to nitrocellulose and immunostained for the acidic and basic keratins and for the keratin filament associated protein, filaggrin, using monoclonal antibodies. All samples contained keratins typical of fetal epidermis at 20 weeks gestation. Presence of filaggrin is variable at this age and depends on the presence of keratinized cells of hair canals. No keratin abnormalities in the fetus at risk for lamellar ichthyosis were detected, however, in one presumably normal biopsy, an abnormally low proportion of the 67 kd keratin and the presence of follicular keratins were evident. These results demonstrate that biochemical analysis of fetal biopsies is possible, thus increasing the diagnostic potential of the fetal biopsy procedure for disorders in which a known protein or antigen is altered in utero.     

Prenatal detection of the autosomal dominant type of congenital hydronephrosis by ultrasonography

We report a family with clearly defined two generation, and probable four generation uropathy due to a congenital malformation of the genitourinary system. There appears to be variation in expression within this family and a severely affected fetus was detected by ultrasonography at 31 weeks gestation.     

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 congenital cystic adenomatoid malformation of the lung by fetal lung biopsy

A case of type III congenital cystic adenomatoid malformation of the lung was successfully diagnosed prenatally by fetal lung biopsy. We performed this procedure at 22 weeks of gestation, using a biopsy gun system under ultrasound guidance. The pregnancy was undisturbed by the procedure but as the condition was incompatible with life, an abortion was performed. The diagnosis was confirmed at post-mortem examination. Fetal lung biopsy appears to be a useful method for prenatal diagnosis of fetal lung disorders.     

Prenatal diagnosis of atypical tay-sachs disease by chorionic villi sampling

We studied a family at risk for atypical TSD in which the index case showed, clinically, a late onset and a gradual psychomotor deterioration and biochemically, a residual hex. A activity in leucocytes. Two prenatal diagnoses of affected fetuses were made in this family, The first one on amniotic cells, the second one on trophoblast biopsy samples. Both of them were confirmed after abortion on cultured cells. Prenatal diagnosis of TSD, even of some atypical forms is possible using trophoblast biopsy, but formal confirmation should be obtained on cultured trophoblasts.     

Prenatal exclusion of duchenne muscular dystrophy by fetal muscle biopsy

A fetal thigh muscle biopsy was performed at 18 weeks and 6 days' gestation using an automatic 18-gauge biopsy needle. A positive immunoreaction with antisera to the amino- and carboxy-terminals of dystrophin excluded Duchenne muscular dystrophy from this at-risk male.     

Prenatal diagnosis of congenital nephrosis by in utero kidney biopsy

The diagnosis of congenital nephrosis is difficult during the antepartum period. The combination of an elevated amniotic fluid alpha-fetoprotein, a negative acetylcholinesterase, and a negative ultrasound examination is highly indicative of congenital nephrosis; however, these findings can also be associated with a normal gestation. This is the first report of pathologic confirmation of congenital nephrosis from an in utero fetal kidney biopsy. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of thalassemia major by fetal blood analysis: Experience with 1000 cases

In this report we have summarized our experience with the prenatal diagnosis of β-thalassemia in 1000 pregnancies followed at least until 12 months after birth. In the majority of these cases, the thalassemia lesion was the nonsense mutation at the codon corresponding to amino acid 39, which produces the hematological phenotype of β-thalassemia. Fetal blood sampling was carried out by placental aspiration, by which a sufficient amount of fetal blood for analysis was obtained in the majority of cases (99 per cent). The fetal mortality associated with fetal blood sampling was 6·3 per cent. Those placental samples contaminated by maternal cells were successfully purified by Ørskov lysis. Fetal blood was analysed by globin chain synthesis on CM–52 columns, which gave reliable results. Two misdiagnoses (0·2 per cent) have been made of which one was due to a non-globin protein co-migrating with the β-chains while the other resulted from a misclassification of the type of thalassemia segregating in the family.     

Prenatal diagnosis of alpha-1-antitrypsin deficiency by fetal blood sampling

Fetal blood sampling for the diagnosis of alpha-1-antitrypsin deficiency using protein isoelectric focusing was carried out in the period 1980–1985. The results of 25 cases from 18 mothers are reported. All had a previous history of a PiZ child affected by liver disease. The method was found to be technically satisfactory and the fetal results were subsequently confirmed in all 18 cases where follow-up was possible. The fetus was found to be PiZ in nine cases and all these pregnancies were terminated. Of the remaining pregnancies three cases aborted or were delivered prematurely and 13 proceeded to term without complications.     

Diagnosis and prenatal diagnosis of epidermolysis bullosa herpetiformis (Dowling-Meara) in a mother,two affected children,and an affected fetus

In utero skin biopsy was performed on a fetus at risk of an uncertain form of epidermolysis bullosa (EB). The mother had produced two affected offspring diagnosed variously as having junctional or dystrophic EB. The two offspring and the fetus were products of different fathers. The mother claimed to have no disease and on clinical examination was without blisters. Examination of the fetal skin biopsy by light and electron microscopy revealed separation of the epidermal sheet from the majority of the biopsy sample, although occasional remnants of basal cells remained associated with the basement membrane. Aggregations of keratin filaments were observed within basal cells of the detached epidermis and in the attached basal cell remnants. The diagnosis was thus suggested to be epidermolysis bullosa Dowling-Meara. Re-review of the clinical and laboratory data from the affected infants revealed a clinical and histological pattern consistent with this diagnosis. Further discussion with the mother revealed that her skin had blistered as a child and that she presently had hyperkeratotic palms and soles. This history is consistent with the autosomal dominantly inherited epidermolysis bullosa herpetiformis (Dowling-Meara). This is the first reported prenatal diagnosis of EB Dowling—Meara. The morphological criteria of intraepidermal blistering and clumped keratin filaments within basal and immediately suprabasal cells characteristic of an affected individual postnatally also identified an affected fetus. There is, however, insufficient experience to be certain that these findings will hold from region to region in the body or among all affected fetuses, and thus prenatal diagnosis on a morphological basis should still be made with caution.     

Prenatal diagnosis of hydrocephalus-stenosis of the aqueduct of Sylvius by ultrasound in the first trimester of pregnancy. Report of two cases

Hydrocephalus-stenosis of the acqueduct of Sylvius sequence (HSAS) is characterized by hydrocephalus, macrocephaly, adducted thumbs, spasticity, agenesis of the corpus callosum and mental retardation. X-linked hydrocephalus is known to be due to mutations in the gene coding for the neural cell adhesion molecule L1 (L1-CAM) and diagnosis is made by identification of a mutation in the L1-CAM gene. Prenatal diagnosis of HSAS is usually suggested on ultrasound examination showing hydrocephalus in a male fetus associated with bilateral adducted thumbs. Mutation screening of the L1-CAM gene is indicated when neuropathological examination shows hypoplasia of the corticospinal tract associated with aqueductal stenosis. We report here two cases of HSAS diagnosed within the same family by ultrasound examination in the first trimester of pregnancy when bilateral adducted thumbs were the only early ultrasound marker. Copyright © 2001 John Wiley & Sons, Ltd.