Journal of Pediatric Genetics - Volume 2, issue 2

Authors: Recker, Florian | Reutter, Heiko | Ludwig, Michael

Article Type: Research Article

Abstract: The oculocerebrorenal syndrome of Lowe is a rare X-linked multisystemic disorder characterized by the triad of congenital cataracts, cognitive and behavioral impairment and a renal proximal tubulopathy in almost all of the patients. Whereas the ocular manifestations and severe hypotonia are present at birth, the renal involvement appears within the first months of life. Patients show progressive growth retardation and may develop a debilitating arthropathy. Treatment is symptomatic and life span rarely exceeds 40 yr. The causative OCRL gene, encodes an inositol polyphosphate 5-phosphatase. OCRL mutations were not only found in classic Lowe syndrome, but also in milder …affected patients, classified as having Dent-2 disease. There is a phenotypic continuum within patients with Dent-2 disease and Lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of enzyme function. Researchers have conducted a large amount of work to understand the etiology responsible for the disease. However, the mechanisms leading to the clinical manifestations are still poorly understood and we are far from an effective therapy. In this review, we have included well-established findings and the most recent progress in understanding Lowe syndrome and Dent-2 disease. Show more

Keywords: Congenital cataracts, cognitive and behavioral impairment, OCRL gene, oculocerebrorenal syndrome, inositol polyphosphate 5-phosphatase, proximal tubulopathy

DOI: 10.3233/PGE-13049

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 53-68, 2013

Authors: Santos, Izabela R. | Fernandes, Ana Paula | Sousa, Marinez O. | Ferreira, Cláudia N. | Gomes, Karina B.

Article Type: Research Article

Abstract: Dyslipidemia is an important etiological factor for development of cardiovascular disease, which is the leading cause of deaths in adults. Given the growing global epidemic of dyslipidemia, lipoprotein metabolism disorders have become an important health problem not only in adulthood, but have also emerged as an increasingly risk factor in childhood. Although several genome-wide association studies in multiple large population-based cohorts of adults and meta-analyses have identified susceptibility genes or loci, especially in lipid-related traits, it is of great importance to evaluate genetic predisposition at an early age. Recent findings suggest that the identification of polymorphisms in the metabolism of …lipids in childhood may help fight subclinical atherosclerosis and its progression to cardiovascular complications in adulthood. Therefore, the aim of this study was to review genetic polymorphisms as risk factors associated with dyslipidemia in children and adolescents. Show more

Keywords: Dyslipidemia, childhood, polymorphism, cardiovascular risk

DOI: 10.3233/PGE-13050

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 69-75, 2013

Authors: Valverde, Diana | Castro-Sánchez, Sheila | Álvarez-Satta, María

Article Type: Research Article

Abstract: Bardet-Biedl syndrome (BBS) is a rare multisystem genetic disease, with high phenotypic and genetic heterogeneity. Rod-cone dystrophy, obesity, polydactyly, hypogonadism, cognitive impairment and renal abnormalities have been established as primary features. There are 17 BBS genes (BBS1-BBS17) described to date, which explain 70–80% of the patients clinically diagnosed, therefore more BBS genes remain to be identified. BBS belongs to a group of diseases known as ciliopathies. In general, ciliopathies and BBS in particular share a partial overlapping phenotype that makes them complicated to diagnose. We present an up-to-date review including clinical, epidemiologic and genetic aspects of the syndrome.

Keywords: Bardet-Biedl syndrome, ciliopathy, BBS genes, BBS proteins

DOI: 10.3233/PGE-13051

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 77-83, 2013

Authors: Oliveira, Camila Ive Ferreira | Fett-Conte, Agnes Cristina

Article Type: Research Article

Abstract: Birth defects (BDs) or congenital anomalies include all structural and functional alterations in embryonic or fetal development resulting from genetic, environmental or unknown causes, which result in physical and/or mental impairment. BDs occur in about 3% of newborn babies and in most cases of pregnancy loss. BDs are a very complex and heterogeneous group of single or multiple changes that, in most cases, are of unknown etiology. Among the risk factors are advanced maternal and paternal ages, parental consanguinity, teratogenic agents such as infectious agents and drugs, and poor nutrition, in particular folic acid deficiency. One of the consequences of …these defects is the high death rate within the first year of life. Information on BDs is becoming increasingly more important throughout the world so that preventive measures can be taken. Knowledge of BDs enables the development of therapeutic and preventive strategies besides adequate genetic counseling. Show more

Keywords: Congenital anomalies, congenital malformation, chromosomal abnormalities

DOI: 10.3233/PGE-13052

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 85-90, 2013

Authors: Haenen, Filip | Alders, Marielle | Dierckx, Elke | Van Schil, Paul | Demeulemeester, Veronique | Mortier, Geert | Desager, Kristine

Article Type: Other

Abstract: Hyper-immunoglobulin E syndrome (HIES) is a rare immunologic disorder. This syndrome is caused by mutations in signal transducer and activator of transcription 3 gene. The described case report showed clinical HIES features such as recurrent bacterial pneumonia, lung cysts, characteristic facial features and a newborn dermatitis. We found a clinical features score of 35 and a positive family history, which, together, made a HIES diagnosis very probable. During DNA analysis, a new, formerly unknown, 1067C→G (p.P356R) mutation, with reference sequence NM_139276.2, was found in the DNA binding site of the STAT3 gene. Both the child and his mother were …affected. Thus, this family is affected by the autosomal dominant, HIES. This case report reveals a formerly unknown mutation, 1067C→G (p.P356R) in this gene. Show more

Keywords: MeSH, STAT3 transcription factor, hyper-Ig E syndrome, autosomal dominant, allergy, immunology, child

DOI: 10.3233/PGE-13053

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 91-96, 2013

Authors: Vazquez, Michelle N. | Gold-von Simson, Gabrielle

Article Type: Other

Abstract: Brugada syndrome (BrS) is rare genetic disorder, which manifests as syncope or sudden death caused by polymorphic ventricular tachycardia. Diagnosis is based on symptoms and characteristic electrocardiography findings. Identification of mutations in SCN5A support the diagnosis, but the yield is low. According to experts, BrS patients with a history of cardiac arrest should have insertion of an automatic implantable cardiac defibrillator and asymptomatic patients can be managed conservatively. Treatment challenges occur in patients with “intermediate” clinical characteristics and in populations where there is paucity of data such as with neonates and children. We discuss the case of a woman …with BrS who is faced with decision challenges in the postpartum period. Should her newborn have testing? When? Will deferment of testing impose an unreasonable uncertainty due to delay of diagnosis? Or conversely, will premature workup impose an unnecessary intervention? Show more

Keywords: Brugada syndrome, genetic testing, neonatal

DOI: 10.3233/PGE-13054

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 97-101, 2013

Authors: Freire, Gabrielle | Russell, Laura | Oskoui, Maryam

Article Type: Other

Abstract: The clinical features associated with terminal 6p deletion syndrome include anterior eye chamber defects, hearing loss, congenital heart anomalies and characteristic facies along with developmental delays. These features overlap with a number of other conditions including CHARGE syndrome. This acronym stands for non-random association of anomalies including coloboma of the eye, heart anomalies, choanal atresia, retardation of growth and development, genital hypoplasia and ear anomalies/deafness now known to be caused by CHD7 mutations. We describe a boy initially diagnosed with CHARGE syndrome who was subsequently found to have a terminal 6p deletion. Screening for 6p deletions in individuals presenting …with atypical CHARGE syndrome may be warranted, with direct consequences for genetic counseling. Show more

Keywords: CHARGE syndrome, 6p deletion syndrome, CHD7 mutation

DOI: 10.3233/PGE-13055

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 103-107, 2013

Authors: Dayal, Devi | Dekate, Parag | Sharda, Sheetal | Das, Ashim | Attri, Savita

Article Type: Other

Abstract: Fanconi-Bickel syndrome is a rare autosomal-recessive disorder caused by defects in the facilitative glucose transporter 2 (GLUT2 ) gene. It is characterized by hepatorenal glycogen accumulation, tubular nephropathy and impaired utilization of glucose and galactose. In this communication, we present the case of a 5-year-old girl who presented with deforming rickets and massive hepatomegaly. Liver biopsy confirmed the diagnosis of glycogen storage disorder. However, the mutation of the SLC2A2 (GLUT2 ) gene was not found. Mutation negative patients with characteristic Fanconi-Bickel syndrome phenotype suggest additional underlying mechanisms that need exploration.

Keywords: Fanconi-Bickel syndrome, hypophosphatemic rickets, glycogen storage disease type XI

DOI: 10.3233/PGE-13056

Citation: Journal of Pediatric Genetics, vol. 2, no. 2, pp. 109-112, 2013