Road to A Rare Diagnosis: A Case Report Exploring Phenotype, Clinical Management and Outcome of a Rare and Novel Unbalanced Translocation causing complete Trisomy 17p

Background: Trisomy 17 is a rare chromosomal disorder with limited existing literature that mostly refer to mosaic Trisomy 17 cases. Our report summarizes the clinical course of a neonate with a Trisomy 17 karyotype der (14;17) (q10; p10), + 17 pat. Key words: Trisomy 17, Unbalanced translocation, Paternal origin

DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis

Down syndrome (DS) is the most common chromosomal disorder. It is responsible for intellectual disability (ID) and several medical conditions. Although men with DS are thought to be infertile, some spontaneous paternities have been reported. The few studies of the mechanism of infertility in men with DS are now dated. Recent research in zebrafish has indicated that overexpression of DYRK1A (the protein primarily responsible for ID in DS) impairs gonadogenesis at the embryonic stage. To better ascertain DYRK1A’s role in infertility in DS, we investigated the effect of DYRK1A overexpression in a transgenic mouse model. We found that overexpression of DYRK1A impairs fertility in transgenic male mice. Interestingly, the mechanism in mice differs slightly from that observed in zebrafish but, with disruption of the early stages of spermatogenesis, is similar to that seen in humans. Unexpectedly, we observed hypogonadotropic hypogonadism in the transgenic mice.

Suspected Down Syndrome in one of non-identical twins in Ile-Ife: A case report

Nigerian women of southwest extraction have the highest rate of dizygotic twinning worldwide, with a reported incidence as high as 49 per 1000 deliveries. Among the risk factors for dizygotic twinning is advanced maternal age, which is also an independent risk factor for Down syndrome (trisomy 21). Down syndrome is the most common chromosomal disorder affecting live born neonates. It occurs very rarely in twins, seen in 14-15 per million non-identical twins. Down syndrome in one of non-identical twins was first reported in Nigeria by Otaigbe in Port Harcourt, in 2007. Herein, we report another case of suspected Down syndrome in one of non-identical twins born to a 41-year-old grand multiparous woman at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun state, Nigeria. Keywords: Down Syndrome; dizygotic; fraternal; dichorionic; diamniotic.

Integrated Quantitative Neuro-transcriptome Analysis of Several Brain Areas in Human Trisomy 21

Background Although Down syndrome (DS) is a trisomy of chromosome 21 being the most frequent human chromosomal disorder mainly associated with variables dysfunctions. Objective In this context, we aimed to analyze and compare the disruption of transcriptome of several brain areas from individuals with DS and euploid controls as a new approach to consider a global systemic differential disruption of gene expression beyond of chromosome 21. Methods We used data from a DNA microarray experiment with ID GSE59630 previously deposited in the GEO DataSet of NCBI database. The array contained log2 values of 17,537 human genes expressed in several aeras of human brain. We calculated the differential gene expression (Z-ratio) of all genes. Results We found several differences in gene expression along the DS brain transcriptome, not only in the genes located at chromosome 21 but in other chromosomes. Moreover, we registered the lowest Z-ratio correlation between the age ranks of 16–22 weeks of gestation and 39–42 years (R 2 = 0.06) and the highest Z-ratio correlation between the age ranks of 30–39 years and 40–42 years (R 2 = 0.89). The analysis per brain areas showed that the hippocampus and the cerebellar cortex had the most different gene expression pattern when compared to the brain as a whole. Conclusions Our results support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network of cognitive and neuroplasticity process as new model to explain the important effect on the neurophenotype of trisomy that occur not only in loci of chromosome 21 but also in genes located in other chromosomes.

DOWN SYNDROME – LONGITUDINAL STUDY OF CLINICAL EVOLUTION AND PSYCHO-SOCIAL IMPLICATIONS

Introduction. Down syndrome is the most common chromosomal disorder, with a worldwide frequency of 1 case in 700 live births. Objectives. Starting from the hypothesis that with the increased life expectancy of the patients with Down syndrome, new phenotypic changes and new dysfunctions are expected to appear, we proposed a longitudinal study to analyze their evolution over a long period of time. Material and method. This is a longitudinal study, based on retrospective research and descriptive evaluation, performed on a group of 81 patients from the case series of the Bihor Regional Center for Medical Genetics from Oradea. Results. We have identified 4 types of evolutionary trends of the clinical signs: stationary, involutive, progressive and with late onset. Conclusions. Knowledge of the natural evolution of the signs and symptoms of the disease is indispensable in the long-term monitoring of patients with Down syndrome. The birth of a child with Down syndrome is a real drama for the family with a strong emotional impact that can be prevented or mitigated by facilitating prenatal diagnosis, psychological counselling, social support and specialized genetic advice.

Estradiol–Testosterone Imbalance Is Associated with Erectile Dysfunction in Patients with Klinefelter Syndrome

Erectile dysfunction (ED) is a frequent sexual disorder in adult men. Klinefelter syndrome (KS) is the most common sex chromosomal disorder and a frequent cause of male hypogonadism. Psychological and cognitive aspects are quite typical in KS and have been linked to ED, while the role of testosterone (T) levels in sexual function of KS subjects has not been fully elucidated. The purpose of the present study is to investigate the role of hormonal disturbances in erectile function of subjects with KS. We conducted a retrospective study involving 52 Klinefelter patients newly diagnosed who never received androgen replacing therapy. All the subjects underwent medical history, accurate physical examination, and blood tests. The International Index of Erectile Function questionnaire (IIEF-EF) score correlated negatively with estradiol/testosterone ratio (E2/T); this correlation remained statistically significant after correction for age (ρ −0.320 p = 0.018). A multiple linear regression analysis identified age and E2/T as the main predictors of IIEF-EF score (R2 0.169 F = 3.848 p = 0.008). Our findings corroborate previous KS data obtained in the general population showing an association between higher E2/T ratio and impaired erectile function. Larger studies are required to better elucidate the pathophysiology of ED in patients with KS.

A rare cause of progressive gait abnormality in a case of Turner syndrome

Turner syndrome is a commonly encountered chromosomal disorder affecting females, while Duchenne muscular dystrophy is a severe X-linked recessive disorder affecting males. Although theoretically possible, very few cases of DMD associated with Turner syndrome have been reported. We report an 8 year old girl who presented with a rare association of Turner syndrome mosaicism (45X/46XringX) with Duchenne muscular dystrophy.

Electroclinical Improvement in a Patient with Ring Chromosome 20 Syndrome Treated with Zonisamide: A Case Report

Ring chromosome 20 or r(20) syndrome is a rare chromosomal disorder, mainly characterized by childhood-onset drug-resistant epilepsy with typical electroencephalographic findings, followed by mild to severe cognitive-behavioral decline. Recent studies support a possible role of the dopaminergic system in the epileptogenesis of this syndrome. We report the case of a 13-year-old female with mosaic r(20) who showed typical disease onset and evolution and a remarkable electroclinical improvement with zonisamide. Epilepsy related to r(20) is often medically intractable. When valproate and lamotrigine are not effective, zonisamide could be further investigated as a therapeutic option, since it acts as antifocal and it has a potential role in the prevention of dopamine depletion.

A case of inversion of chromosome 4 and an unbalanced transloca- tion between the short arm of chromosome 4 and long arm of chromosome 18 in a girl: evolution of clinical and electroencephalographic manifestations

We report a case of a girl with a chromosomal disorder that has never been described in the literature: inversion of chromosome 4 with an unbalanced translocation between the short arm of chromosome 4 and long arm of chromosome 18. Clinical manifestations of this syndrome included severe growth retardation, very slow weight gain, optic nerve hypoplasia, pronounced delay in mental and motor development, and epilepsy with focal hemiclonic fever-related seizures of varying location. The patient has multiple stigmas of dysembryogenesis, but no abnormalities in the development of internal organs. The somatic status is complicated by chronic liquid aspiration and sleep apnea. Magnetic resonance imaging has demonstrated agenesis of the corpus callosum. In this article, we have summarized the results of clinical observation and electroencephalography findings obtained during several years. The type of epilepsy in this girl does not match Wolf–Hirschhorn syndrome (which is determined by her karyotype), but is similar to epilepsy in patients with aberrations of the long arm of chromosome 18.

Nursing care of a child with Down syndrome suffering from leukemia

Down syndrome [DS] is the most common chromosomal disorder in the population manifested by intellectual disabilities of varying degrees, often accompanied by disorders in organ systems. Compared to the children without DS, these children have a greater risk of developing malignancy such as acute leukemia. Leukemia is a malignancy of blood cells and lymph nodes and the most common form of cancer in children. Its treatment in children with DS is more complex compared to children without this syndrome. The complexity of a child’s condition with Down syndrome, caused by cancer, requires a holistic approach to address the difficulties both the child and the parents are facing. Providing especially emotional parent support is essential because parents are usually overwhelmed by painful and powerful emotions. Particular attention is paid to communication in order to reduce the feeling of sadness, fear, anxiety and helplessness