Early-infantile galactosialidosis: Prenatal presentation and postnatal follow-up

Galactosialidosis (GS) is an autosomal recessive condition caused by combined deficiency of the lysosomal enzymes β-galactosidase and α-neuraminidase. The combined deficiency has been found to result from a defect in protective protein/cathepsin A (PPCA), an intralysosomal protein which protects these enzymes from premature proteolytic processing. The most severe form of GS, the early-infantile form, results in early onset of edema, ascites, visceromegaly, and skeletal dysplasia. We report a case of early-infantile GS in a male infant who presented with nonimmune fetal hydrops (NIH), “coarse” facial appearance, massive fluid-filled inguinal hernias, multiple telangiectasia, and diffuse hypopigmentation; he subsequently developed visceromegaly. The diagnosis of GS was confirmed biochemically and the defect in PPCA characterized at the protein level. Examination of fetal peripheral blood smears sampled at 30 weeks gestation demonstrated vacuolation of lymphocytes, suggesting blood film examination may be a useful screening tool for cases of NIH where a metabolic disorder is suspected. Skeletal radiography at birth demonstrated punctate epiphyses of the femora, calcanei, and sacrum. We present a discussion of and differential diagnosis for this radiographic finding. To the best of our knowledge, this is the first case of early-infantile GS presenting with stippled epiphyses. Am. J. Med. Genet. 85:38–47, 1999. © 1999 Wiley-Liss, Inc.     

Functional disomy of Xp: prenatal findings and postnatal outcome

We report on trisomy of the short arm of the X chromosome (Xp11.2 --> pter) due to a de novo unbalanced X;13 translocation diagnosed prenatally in a female fetus. Amniocentesis was performed at 20-weeks' gestation following ultrasound finding of a Dandy-Walker malformation. The trisomy of Xp11.2 --> pter was confirmed with fluorescence in situ hybridization (FISH), using an X chromosome painting probe and telomeric FISH probes specific for the short arm of chromosome X. The karyotype was defined as 46,XX,der(13)t(X;13)(p11.2;p11.2). Molecular analysis suggested that the extra Xp material was of paternal origin. FISH analysis with an XIST probe showed that the derivative chromosome 13 did not include the XIST locus at the X-inactivation center (XIC). A complex phenotype was seen at birth including macrosomia, facial dysmorphism with preauricular tag, congenital heart defects, and structural brain malformations. Because the derivative chromosome was not subject to X inactivation, functional disomy of Xp11.2 --> pter most likely accounts for the abnormal phenotype in this patient.     

Deficits in fixed-interval performance following prenatal and postnatal lead exposure.

Female rats were exposed daily to 750 mg/kg of lead acetate via a restricted watering schedule for 70-80 days prior to mating and then throughout pregnancy and nursing. At weaning, litters from half of the lead dams were placed directly on treatment for the duration of the experiment. These manipulations yielded 3 groups: Group Pb/Pb, offspring exposed during pre- and postweaning periods; Group Pb/C, offspring exposed only during preweaning periods: and Group C/C, control offspring. Beginning at 42-49 days of age, postnatal, offspring were shaped to bar press under a fixed-interval, 1-min schedule (FI1) and then given 20 sessions, each 45 min in length. Analyses revealed that Group Pb/Pb received fewere reinforcements across sessions than the other 2 groups, which did not differ. However, when the Pb/Pb offspring did receive reinforcement, they exhibited the scalloped pattern of responding characteristic of fixed-interval schedules.     

Malformations of the liver: Some prenatal and postnatal developmental aspects

The discovery of a large articulated lobe weighing 165.4 g dependent from the anterior margin of the left liver lobe in a 93-year-old female culminated two decades of observation of anomalous liver conditions in anatomic cadavers. When this data was compared with the information previously recorded from a series of 52 perinatal livers, remarkable discrepancies between the adult and perinatal incidences of various anomalous manifestations were noted. Ectopic accessory lobes were very rare in our adult series as well as in the groups reported in literature reviews. However, they were a relatively common occurrence in the perinatal cases, as were also gallbladder bridges of hepatic tissue, hypertrophic papillary lobes, and marked accessory fissures. In contradistinction, marginal accessory lobes were not noticed in any of the perinatal livers. Because the liver undergoes considerable postnatal reformation, it was concluded that most ectopic lobes, gallbladder bridges, hypertrophic caudate lobe extensions, and accessory fissures disappear during postnatal remodeling, whereas marginal accessory lobes may result from retention of the original perinatal boundaries of the anterior liver margins. © 1996 Wiley-Liss, Inc.     

CCMG guidelines: prenatal and postnatal diagnostic testing for uniparental disomy

The aim of this statement is to provide clinicians, cytogeneticists and molecular geneticists of the Canadian College of Medical Geneticists (CCMG) a comprehensive review of the role of UPD in constitutional genetic diagnosis and to provide a guideline as to when investigation for UPD is recommended. Members of the CCMG Cytogenetics, Molecular Genetics, Clinical Practice, and Prenatal Diagnosis committees reviewed the relevant literature on uniparental disomy (UPD) in constitutional genetic diagnosis (May 2010). Guidelines were developed for UPD testing in Canada. The guidelines were circulated for comment to the CCMG members at large and following appropriate modification, approved by the CCMG Board of Directors (July 2010).     

Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.

We report on a male newborn infant, a compound carrier of heterozygous mutations in the FGFR3 gene causing achondroplasia and hypochondroplasia. The mother has achondroplasia and carries the common G1138 (G380R) mutation in the FGFR3 gene; the father has hypochondroplasia due to the C1620A (N540K) mutation in the same gene. The fetus was found to carry both mutations diagnosed prenatally by amniocentesis at 17.6 weeks of gestation, following maternal serum screening which showed an increased risk for Down syndrome (1:337). Detailed fetal ultrasound studies showed a large head, short limbs, and a small chest at 22 weeks of gestation. The changes were more severe than those of either achondroplasia or hypochondroplasia. The patient was born by cesarean section at 38 weeks of gestation and had rhizomelic shortness of the upper and lower limbs with excess skin folds, large head, enlarged fontanelles, frontal bossing, lumbar gibbus, trident position of the fingers, and a narrow chest with a horizontal line of demarcation at the narrowest area of the chest. Skeletal radiographs showed shortness of the long bones and flare of metaphyses. He had respiratory difficulties and was treated with nasal prongs. Seizures developed on day 2 of life and recurred on day 9 and responded to treatment with phenobarbital. Brain computed tomographic scan showed possible grey matter heterotopia, partial agenesis of the corpus callosum, and cortical dysplasia. To our knowledge, there are only two previously published cases of compound heterozygous achondroplasia-hypochondroplasia patients. The diagnosis was confirmed by DNA mutation analysis of the FGFR3 gene in both cases.     

Trisomy 9 confined to the placenta: prenatal diagnosis and neonatal follow-up.

Chorionic villus sampling (CVS), performed on a woman in the 23rd menstrual week because of bilateral fetal hydronephrosis and suspected intrauterine growth retardation (IUGR), documented trisomy 9 in all cells examined. Chromosomes of amniocytes and fetal blood lymphocytes were normal. The ongoing pregnancy was monitored closely, and at 37 weeks, a phenotypic normal male infant was delivered. Multiple placental biopsies showed 47,XY,+9, while a repeat chromosome analysis of the infant and biopsies from the amniotic membrane were normal (46,XY). This case further emphasizes the association between placental aneuploidy and IUGR. To our knowledge, nonmosaic trisomy 9 in CVS confined to the chorionic villi and later confirmed in the placenta has not been reported previously.     

Clinical presentation of postnatal and non-postnatal depressive episodes

BACKGROUND: The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression. METHOD: In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group. RESULTS: The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression. CONCLUSIONS: The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.     

Dietary prenatal choline supplementation alters postnatal hippocampal structure and function

Choline, a compound present in many foods, has recently been classified as an essential nutrient for humans. Studies with animal models indicate that the availability of choline during the prenatal period influences neural and cognitive development. Specifically, prenatal choline supplementation has been shown to enhance working memory and hippocampal long-term potentiation (LTP) in adult offspring. However, the cellular mechanisms underlying these effects remain unclear. Here we report that choline supplementation, during a 6-day gestational period, results in greater excitatory responsiveness, reduced slow afterhyperpolarizations (sAHPs), enhanced afterdepolarizing potentials (ADPs), larger somata, and greater basal dendritic arborization among hippocampal CA1 pyramidal cells studied postnatally in juvenile rats (20-25 days of age). These data indicate that dietary supplementation with a single nutrient, choline, during a brief, critical period of prenatal development, alters the structure and function of hippocampal pyramidal cells.     

Development of gammadelta thymocyte subsets during prenatal and postnatal ontogeny

In this report, we describe 12 subpopulations of porcine gammadelta thymocytes based on their expression of CD1, CD2, CD4, CD8- isoforms and CD45RC. Our data suggest that gammadelta thymocytes can be divided into two major families: (a) one large family of CD4-gammadelta thymocytes that could be further subdivided according to the CD2/CD8alphaalpha phenotype and (b) a small family of CD4+ gammadelta thymocytes bearing CD8alphabeta and possessing certain unusual features in comparison with other gammadelta thymocytes. Maturation of gammadelta thymocytes within the CD4- family begins with proliferation of the CD2+ CD8- CD1+ CD45RC- gammadelta common precursor. This developmental stage is followed by diversification into the CD2+ CD8alphaalpha+, CD2+ CD8- and CD2- CD8- subsets. Their further maturation is accompanied by a loss of expression of CD1 and by increased expression of CD45RC. Therefore, individual subsets develop from CD1+ CD45RC- through CD1- CD45RC- into CD1- CD45RC+ cells. On the other hand, gammadelta thymocytes within the CD4+ family bear exclusively CD8alphabeta, always express CD1, but may coexpress CD45RC. These cells have no counterpart in the periphery. Our observations suggest that all peripheral CD8+ gammadelta T cells express CD8alphaalpha and that two subsets of these cells differing in major histocompatibility complex II expression, occur. We propose that one subset acquires CD8alphaalpha in the thymus while the second acquires CD8alphaalpha as a result of stimulation in the periphery.     

Arrays in postnatal and prenatal diagnosis: An exploration of the ethics of consent

The introduction of genome-wide arrays in postnatal and prenatal diagnosis raises challenging ethical issues. Here, we explore questions with regard to the ethics of consent. One important issue is whether informed consent for genome-wide array-based testing is in fact feasible, given the wide range of possible outcomes and related options. The proposed alternative of "generic consent" will have to be studied in practice. From an ethical point of view, the question is whether consent would still be sufficiently "informed" in a generic approach. Another issue that has not yet been given much attention is how far parents, or pregnant women and their partners, should be allowed to determine the range of possible outcomes that will or will not be reported back to them. The scope and limits of parents' and prospective parents' right to know or not to know are far from clear. The complex normative issues on the content and weight of these rights can only be answered by taking full account of the rights and interests of all the parties involved: prospective and actual parents, children, and relatives. This paper is the result of a working group meeting preceding the European Society of Human Genetics 2011 Conference, where these issues were addressed.     

45,X/46,XY Mosaicism. Contrast of prenatal and postnatal diagnosis

The process of prenatal diagnosis is unique in that the diagnosis and prognosis are made without seeing the patient. 45,X/46,XY mosaicism presents a special problem in this regard. The phenotype of 45,X/46,XY postnatally diagnosed children (pediatric group) was compared to that of 6 fetuses who were diagnosed from 7,000 amniocenteses (prenatal group). These amniocenteses were performed primarily because of an increased risk of chromosome abnormality. The pediatric group (age birth—18 yr) were all phenotypically abnormal, although none were mentally retarded. Seven patients presented with ambiguous genitalia, while 2 had primary amenorrhea. Sexual assignment was changed in 2. Abnormalities included rudimentary phallus, urogenital sinus, hypospadias, undescended testes, and short stature. All 9 patients required at least one surgical procedure. In contrast, the prenatally diagnosed fetuses (ages 3 months to 31/2 yr) were all phenotypically normal males. Four were noted to have male genitalia on ultrasonography. Thus, the phenotype of 45,X/46,XY mosaicism in prenatally diagnosed fetuses can be markedly different from that of individuals diagnosed postnatally. This must be considered when counseling patients.     

Consanguinity related prenatal and postnatal mortality of the populations of seven Pakistani Punjab cities.

A retrospective study was conducted on prenatal and postnatal mortality among the populations of seven cities in the Pakistani province of Punjab. Consanguineous marriages were strongly favoured and the coefficients of inbreeding (F) for the present generation in each locality ranged from 0.0236 to 0.0286. There was a highly significant relationship between the degree of inbreeding and mortality, with most consanguinity related deaths reported in the neonatal, infantile, and childhood periods. The findings strongly suggest that consanguinity may play a major role in the high rates of postnatal mortality observed in Pakistani communities now resident in the United Kingdom.     

Effects of prenatal cocaine exposure and postnatal environment on child development

Studies on the long-term developmental effects of in utero cocaine exposure are few and the small number of studies published do not consider the postnatal environment. The present investigation was conducted to quantify the role that postnatal environment played compared to prenatal exposure. Four groups of 25 infants, each assessed at 12 months of age, were included in the study design: 1) noncocaine-exposed children residing with their biological parents in low socioeconomic environments, 2) cocaine-exposed children living with their biological parents in low socioeconomic environments, 3) noncocaine-exposed children adopted at birth in middle to upper-middle socioeconomic environments, and 4) cocaine-exposed children adopted at birth. Infants were assessed by the Uzgiris-Hunt Ordinal Scales of Infant Psychological Development, the Fagan Test of Infant Intelligence, and the Infant Monitoring Questionnaire. Height and head circumference were measured. Gender and ethnicity were controlled statistically. Significant differences were found in cognitive functioning, in fine motor development, and in physical growth between control and prenatally cocaine-exposed children. Adoption enhanced cognitive functioning and fine motor skills among infants not exposed to cocaine prenatally, but had no apparent effect on infants prenatally exposed to cocaine. Am. J. Hum. Biol. 12:417–428, 2000. © 2000 Wiley-Liss, Inc.     

Keratin phenotype of human thymic epithelium during prenatal and postnatal development

Central Laboratory of Neuroanatomy, and Laboratory of Embryonic Histogenesis, Research Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 1, pp. 87–90, January, 1991.