Abstract Many new microdeletion syndromes have been characterized in the past decade, including 2p15-p16.1 microdeletion syndrome. More than 10 patients with this syndrome have been described. Recently, we encountered two additional patients with 2p15-p16.1 microdeletion syndrome. All patients showed variable degrees of intellectual disability, with the autistic features characteristic of this syndrome. Seven out of 16 patients (44%) showed structural abnormalities in the brain, which is also an important feature of this syndrome. The shortest region of microdeletion overlap among the patients includes two genes, USP34 and XPO1. Although these genes have some functional relevance to cancer, they have not been associated with neurological functions. Diagnosis of additional patients with 2p15-p16.1 microdeletion syndrome and identification of pathogenic mutations in this region will help identify the genes responsible for the neurological features of the syndrome.
Abstract The most common form of male infertility is a low sperm count, known as oligozoospermia. Studies suggest that oligozoospermia is associated with epigenetic alterations. Epigenetic alterations in sperm, which may arise due to the exposure of gametes to environmental factors or those that pre-exist in the sperm of infertile individuals, may contribute to the increased incidence of normally rare imprinting disorders in babies conceived after assisted reproductive technology using the sperm of infertile men. Genomic imprinting is an important developmental process whereby the allelic activity of certain genes is regulated by DNA methylation established during gametogenesis. The aberrant expression of several imprinted genes has been linked to various diseases, malignant tumors, lifestyle and mental disorders in humans. Understanding how infertility and environmental factors such as reproductive toxicants, certain foods, and drug exposures during gametogenesis contribute to the origins of these disorders via defects in sperm is of paramount importance. In this review, we discuss the association of epigenetic alterations with abnormal spermatogenesis and the evidence that epigenetic processes, including those required for genomic imprinting, may be sensitive to environmental exposures during gametogenesis, fertilization and early embryonic development. In addition, we review imprinting diseases and their relationships with environmental factors. While the plasticity of epigenetic marks may make these more susceptible to modification by the environment, this also suggests that aberrant epigenetic marks may be reversible. A greater understanding of this process and the function of epidrugs may lead to the development of new treatment methods for many adult diseases in the future.
Abstract Undescended testis (cryptorchidism) is a common structural birth defect, i.e. congenital abnormality of the male genital organs and increasing trend in its birth prevalence was reported in some countries. The aim of this study was to analyze the recorded annual birth prevalence of isolated undescended testis (IUT) in the population-based large dataset of the Hungarian Congenital Abnormality Registry for the period between 1962 and 2011, i.e. during the last 50 years. Cases with IUT reported after births were evaluated, and their annual rate per 1000 live-births was calculated. The rates of cases with IUT were compared with the so-called true rate of IUT measured in a previous clinical-epidemiological study based on the personal examination of 10 203 newborn infants. The birth prevalence of cases with recorded IUT in Hungary was lower than expected based on the true rate of IUT. Thus the two waves in the rate of IUT were connected with the different completeness of reporting. In conclusion the birth prevalence of cases with IUT in Hungary did not indicate a real increasing trend during the last 50 years.
Abstract The purpose of this study was to retrospectively investigate the causes of failure in the first operation and the revision procedure for patients with congenital scoliosis due to hemivertebra. Nineteen patients who underwent the revision operations because of failure in the first operation were included in this study. All the malformations were identified as fully segmented hemivertebra, including 16 cases in thoracolumbar vertebra (T10: three patients; T12: seven patients; L1: six patients), and three cases in thoracic vertebra (T8). The causes of failure in the first operation and the outcome of revision procedure for patients were retrospectively analyzed. All patients were successfully performed the personalized revision surgeries. The failure reasons of the first operation included limitations of the first operation procedure, no or incomplete resection of the malformed hemivertebra, improper operation during surgery, improper internal fixation material, and improper internal fixation scope. The average postoperative scoliosis Cobb's angle and kyphosis Cobb's angle were corrected from 54.1° preoperatively to 23.1° postoperatively, and 59.3° preoperatively to 25.8° postoperatively, respectively. The average postoperative distance between the C7 plumb line and the center sacral vertical line was decreased from 2.5 cm preoperatively to 1.5 cm postoperatively. The average follow-up period was 2.2 years. No serious complication was observed. The cause of the failure of the first operations for the congenital scoliosis due to hemivertebra is verified. Our study may provide a basis for the treatment of congenital scoliosis due to hemivertebra.
Abstract Short-rib polydactyly syndrome type III is an autosomal recessive lethal skeletal ciliopathy, which is phenotypically similar to nonlethal asphyxiating thoracic dystrophy. Mutations in DYNC2H1 have been identified in both of these disorders, indicating that they are variants of a single disorder. However, short-rib polydactyly syndrome type III is the more severe variant. Here, we report novel compound heterozygous mutations in DYNC2H1 (p.E1894fsX10 and p.R3004C) in a patient with typical short-rib polydactyly syndrome type III phenotype. R3004 is located within the microtubule-binding domain of DYNC2H1, and its substitution is predicted to disrupt the interaction with microtubules. Considering the severe phenotype of our patient, our findings suggest that R3004 may be a key residue for the microtubule-binding affinity of dynein.
Abstract Hairy polyps are rare developmental lesions, which present as masses mainly consisting of fatty tissue covered by skin, seldom localized in the nasopharynx, causing respiratory obstruction. We describe the case of a female newborn affected by a hairy polyp arising from the left Eustachian tube, who presented severe respiratory distress soon after birth. The polyp was successfully removed transorally under videoendoscopic guidance. This case highlights the importance of including hairy polyp in the differential diagnosis of respiratory distress at birth because this type of tumor can be lethal and requires prompt treatment. A transoral endoscopy-guided approach can allow successful and minimally invasive excision even in a newborn.
Abstract Holoprosencephaly (HPE) is a rare brain abnormality characterized by an incomplete cleavage of the primitive prosencephalon of forebrain during early embryogenesis. To determine the clinical characteristics and outcome of fetuses with HPE, we retrospectively analyzed nine patients who were prenatally diagnosed as fetal HPE by ultrasounds. The mean diagnostic weeks were 20 weeks of gestation. Two cases died within one day after birth. The chromosomal examinations were performed in seven cases (trisomy 18: n = 2; trisomy 13: n = 2; 45,XX,der(18)t(18;21)(p10;p10)mat: n = 1; normal karyotype: n = 2). In our HPE cases, most cases had serious facial anomalies and poor prognosis. Our data suggested that the early prenatal diagnosis of HPE allowed time for parental counseling and delivery planning.
Abstract We encountered a patient with a fetal cytomegalovirus infection manifesting as pancytopenia and thoracic hypoplasia. The fetal anemia was treated by transfusion via the umbilical cord, and did not progress after 22 weeks' gestation. The neutropenia resolved spontaneously, and only thrombocytopenia was persistent at birth. The severe thoracic hypoplasia led to pulmonary hypertension and required intensive postnatal respiratory management. Our experience suggests that pancytopenia is a possible manifestation in fetuses infected with cytomegalovirus. This may be transient, resolving spontaneously during fetal life; however, caution should be taken with blood counts, particularly platelet counts, after delivery. In addition, clinicians should carefully follow the thoracic volume in cytomegalovirus-infected fetuses and consider the possibility of postnatal severe respiratory insufficiency.
Abstract Developmental Origins of Health and Disease theory stems from large-scale epidemiologic observation. The presumed mechanism for this hypothesis includes epigenetic changes; however, it remains to be elucidated if individuals with intrauterine growth retardation and epigenetic changes confirmed at the molecular level are indeed susceptible to adult-onset disease. Here we document three individuals with Russell-Silver syndrome, a prototypic condition caused by hypomethylation of the differently methylated imprinting center region 1 (ICR1) between the IGF2 and H19 loci on chromosome 11p15. At follow-up, the three patients developed adult-onset diseases such as obesity, hypertension, and diabetes mellitus in their early 20s. The presence of molecularly confirmed epigenetic changes in these patients provides a biological basis for Barker-Brenner's theory at an individual level.