1,721,044 research outputs found
Medications in pregnancy and lactation.
No full textThe best way to provide pregnant women with correct information about the risks related to therapy in pregnancy is to consult a teratology information service. A further activity of teratology information services is in conducting prospective studies, thus playing an important role in postmarketing surveillance. This methodology also allows for the provision of counseling for newly marketed drugs, for which there are usually no published data, by sharing the unpublished follow-up data obtained by each teratology information service
Genetic susceptibility to teratogens: State of the art.
No full textThere is evidence that the susceptibility to the teratogenic effect of drugs within human populations
varies extremely from one individual to another, even after identical exposures. One of the factors that
may explain these interindividual differences is the genetic makeup in the pharmacokinetics and pharmacodynamics
of the respective drugs. In fact, both maternal and embryonic/fetal genotypes can affect
placental transport, absorption, metabolism, distribution and receptor binding of an agent, influencing its
teratogenicity. We have reviewed the literature and commented on the reported correlations between
genetic factors and drug-induced birth defects. There is still a clear lack of knowledge regarding this
issue and the available data are often conflicting. However, the identification of specific polymorphisms
associated with predisposition to teratogenesis may allow in the future the development of personalized
non-teratogenic therapies for pregnant women
Early pediatric palliative care involvement in a child with a large deletion of the short arm (p) of chromosome 10: a case report
Full text linkBackground: We present a case of a Chinese child with one of the largest terminal deletions (21 Mb) of the short arm of chromosome 10 (10p) reported to date. Distal monosomy 10p is a rare chromosomal disorder characterized by intellectual disability, postnatal growth retardation, structural birth defects and dysmorphisms. Mutations in certain 10p regions have been associated with distinct clinical features, but the real weight of each component cannot be estimated in a large deletion like that of our child; therefore, long-term prognosis is difficult to predict precisely, although it certainly foresees a severe impact on the psychomotor development of the child.Case Description: Diagnosis was made in the early neonatal period because of several dysmorphic features and multiple organ involvement. Since the patient's care needs were complex, the Pediatric Palliative Care (PPC) and Pain Service team was involved as a case manager and coordinator from the beginning. In the Veneto region of Italy, our PPC center offers a palliative care approach, through the national health system, embedded with curative-restorative care providing many support activities (such as physiotherapy, physiological support and home assistance) valuable for patients and their families' quality of life. Despite overlap in many characteristics of our child and other children who receive PPC services, the experience of children who have rare genetic conditions and undetermined prognosis with PPC services is still largely unknown. Periodic hospitalization for multidisciplinary follow-up and reassessment of patient's needs were arranged and any rehabilitation program focused on improving her skills was followed. At 5 years of age, her medical condition is controlled and well managed.Conclusions: This case represents a good example of complex care management by the PPC team, which takes into account the patient's and family's needs enhancing their quality of lives, as reported and underlined by parents themselves. This approach could be considered for other children with rare medical conditions without a definite prognosis
Genetics & Epigenetics of Hereditary Deafness: An Historical Overview
Full text linkHearing loss (HL) is one of the most common sensory impairments worldwide and represents a critical medical and public health issue. Since the mid-1900s, great efforts have been aimed at understanding the etiology of both syndromic and non-syndromic HL and identifying correlations with specific audiological phenotypes. The extraordinary discoveries in the field of molecular genetics during the last three decades have contributed substantially to the current knowledge. Next-generation sequencing technologies have dramatically increased the diagnostic rate for genetic HL, enabling the detection of novel variants in known deafness-related genes and the discovery of new genes implicated in hearing disease. Overall, genetic factors account for at least 40% of the cases with HL, but a portion of affected patients still lack a definite molecular diagnosis. Important steps forward have been made, but many aspects still have to be clarified. In particular, the role of epigenetics in the development, function and pathology of hearing is a research field that still needs to be explored. This research is extremely challenging due to the time- and tissue-dependent variability of the epigenetic changes. Multisystem diseases are expected to be investigated at first: specific epi-signatures have been identified for several syndromic disorders and represent potential markers for molecular diagnostics
Pharmacologic treatment of hyperthyroidism during pregnancy.
No full textClinical hyperthyroidism has been associated with an increased risk of maternal, fetal, and neonatal complications. The available antithyroid drugs are methimazole/carbimazole and propylthiouracil. Several case reports and some epidemiologic studies suggest that methimazole/carbimazole exposure during the first trimester of pregnancy is associated with an increased risk of congenital malformations, including ectodermal anomalies, choanal atresia, esophageal atresia, and omphalocele. However, the absolute risk appears to be very small, and it remains unclear whether the association is driven by the maternal disease, the medication, or the combination of both factors. Propylthiouracil exposure has not been associated with an increased risk of congenital malformations and is the recommended drug during the first trimester of pregnancy. Since propylthiouracil-induced hepatotoxicity has been reported in approximately 0.1% of exposed adults and the number of case-reports of severe liver injury is increasing, treatment with low dose methimazole during the second and third trimesters should be considered. Until now, there has been no evidence that children prenatally exposed to methimazole/carbimazole or propylthiouracil have an increased risk of neurodevelopmental delay
Congenital pulmonary airway malformation (CPAM) [congenital cystic adenomatoid malformation] associated with tracheoesophageal fistula and agensesis of the corpus callosum.
No full textEpigenetics of pregnancy: looking beyond the DNA code
Full text linkEpigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal–fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders
Characterization of Two Novel PNKP Splice‐Site Variants in a Proband With Microcephaly, Intellectual Disability, and Multiple Malformations
Full text link: Polynucleotide kinase phosphatase (PNKP), encoded by the PNKP gene, is a DNA processing enzyme involved in double-strand break and single-strand break repair pathways, which are essential for genome stability and for the correct development and maintenance of human nervous system. PNKP biallelic loss-of-function variants have been associated with a broad spectrum of neurological anomalies, ranging from congenital microcephaly with intellectual disability and seizures (MCSZ), to later onset forms of ataxia-oculomotor apraxia (AOA4) or peripheral neuropathy (CMT2B2). We report the atypical clinical manifestations of a patient with severe microcephaly, short stature, developmental delay, conductive hearing loss, and tracheoesophageal malformation, in the absence of seizures. Whole exome sequencing analysis identified two novel, compound heterozygous splice-site variants in the PNKP gene (NM_007254.4): c.1448+1G > A and c.199-8_199-5del. To demonstrate the effect of both variants on the splicing process and prove their pathogenicity, we performed a hybrid minigene assay, which successfully highlighted a deleterious impact on the transcript, particularly regarding the c.199-8_199-5del variant. The uncommon clinical features of the proband and the identification of two newly associated pathogenic variants add further evidence to the allelic and phenotypic heterogeneity of the PNKP locus
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