Fetal skin biopsy in prenatal diagnosis of some genodermatoses

Abstract

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.

Prenatal Diagnosis of Lamellar Ichthyosis by Direct Mutational Analysis of the Keratinocyte Transglutaminase Gene

“…In families at risk for LI, prenatal diagnosis may be proposed based on fetal skin biopsy at around 24 weeks of gestation (Anton-Lamprecht, 1981;Bakharev et al, 1990). However, in selected cases, a molecular analysis of the TGK gene in chorionic villus samples or amniotic fluid may be offered at an early stage of pregnancy.…”

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

“…Moreover, based on studies of postnatal skin of affected individuals, it is likely that EB Dowling-Meara is a subtype of EB simplex which can show variable expression among families. While there has now been extensive experience with prenatal diagnosis of recessive dystrophic EB and junctional EB (Anton-Lamprecht, 1984;Anton-Lamprecht et al, 1987;Bakharev et al, 1990;Holbrook et al, 1992), concerns about regional variation in expression of the disorder and the timing of onset were considered when these diagnoses were first performed. For these forms of EB there are also immunohistochemical markers that can be used to augment the morphological diagnosis and add further assurance of an accurate evaluation (Goldsmith and Briggaman, 1983;Fine et al, 1984Fine et al, , 1988Fine et al, , 1990Kennedy et al, 1985;Heagerty et al, 1987;Schofield et al, 1990;Verrando et al, 1991).…”

“…Prenatal diagnosis of junctional (Rodeck et al, 1980;Loefberg et al, 1983;Anton-Lamprecht, 1981, 1984Heagerty et al, 1986;Fine et al, 1990) and recessive dystrophicEB (Ant0n-Lamprecht etal., 1981;Baueretal., 1986;Fineetal., 1988Fineetal., ,1990Bakharev et al, 1990) has been successfully accomplished using samples of fetal skin obtained by fetal skin biopsy at 19-21 weeks' gestation. The diagnosis ofjunctional EB is based on the site of the split, the absence or hypoplastic development of hemidesmosomes in the fetal skin samples, and the diminished or absent expression of particular basement zone antigens as revealed by immunohistochemical labelling of the skin samples (Kennedy et al, 1985;Heagerty et al, 1986;Fine et al, 1990;Schofield et al, 1990;Verrando et al, 1991).…”

Intrauterine Diagnosis of Genodermatoses

“…In the beginning, a "blind" method was used to obtain fetal skin, with a very low efficiency and high rates of maternal and fetal injuries or infection [4]. Later, new techniques were developed, and FSB was performed with the aid of fetoscopy or ultrasonography [5]. This procedure was performed relatively late in pregnancy, between 15 and 22 weeks gestation [6].…”

“…Nowadays, FSB is hardly utilized, due to the introduction of newer molecular diagnostic procedures. FSB is an invasive method, prone to false-positive (due to mechanical trauma) and -negative (due to inadequate skin sampling) results [5]. Additionally, it has risk for fetal loss (1-3 %), amniotic fluid leakage, and fetal scarring [8], and the number of centers with the experience and expertise to perform this technique is becoming increasingly low [9••].…”