Identification of a founder effect involving n.197C>T variant in RMRP gene associated to cartilage-hair hypoplasia syndrome in Brazilian patients.

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.

Sickle-Cell Disease and Stroke: Quality of Life of Patients in a Chronic Transfusion Regimen from the Caregivers' Perspective.

Strokes affect up to 10% of children with sickle-cell disease (SCD). The most commonly used strategy to prevent a first-time stroke or its recurrence is to perform periodic red blood cell transfusions. This article aims to evaluate the quality of life (QoL) of children and adolescents with SCD undergoing a chronic transfusion regimen (CTR) for stroke prophylaxis, according to their caregivers' perception.

A Systematic Review and Meta-Analysis of Enzyme Replacement Therapy in Late-Onset Pompe Disease.

Unlabelled: Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD).

Methods: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes.

Identification of Novel and Recurrent Variants in a Series of Brazilian Patients with Cartilage-Hair Hypoplasia: McKusick Syndrome.

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder caused by pathogenic variants of the gene and characterized by metaphyseal bone dysplasia associated with hypotrichosis, immunodeficiency, and predisposition to malignancy. However, the genotype-phenotype correlation in CHH is not well understood. Here, we report a single country cohort of 23 Brazilian patients with clinical and radiological features consistent with CHH.

miRNA Genetic Variants Alter Their Secondary Structure and Expression in Patients With RASopathies Syndromes.

RASopathies are a group of rare genetic diseases caused by germline mutations in genes involved in the RAS-mitogen-activated protein kinase (RAS-MAPK) pathway. Whole-exome sequencing (WES) is a powerful approach for identifying new variants in coding and noncoding DNA sequences, including miRNAs. miRNAs are fine-tuning negative regulators of gene expression.

A rapid and accurate methylation-sensitive high-resolution melting analysis assay for the diagnosis of Prader Willi and Angelman patients.

Background: Prader Willi (PWS) and Angelman (AS) syndromes are rare genetic disorders characterized by deletions, uniparental disomy, and imprinting defects at chromosome 15. The loss of function of specific genes caused by genetic alterations in paternal allele causes PWS while the absence in maternal allele results AS. The laboratory diagnosis of PWS and AS is complex and demands molecular biology and cytogenetics techniques to identify the genetic mechanism related to the development of the disease.

Respiratory manifestations in late-onset Pompe disease: a case series conducted in Brazil.

Objective: To describe respiratory function in a series of patients with late-onset Pompe disease after the definitive diagnosis and before enzyme replacement therapy.

Methods: This was a cross-sectional study involving patients with a definitive molecular diagnosis of late-onset Pompe disease. The data analyzed included age at symptom onset; age at definitive diagnosis; type of initial symptoms; time from symptom onset to diagnosis; FVC in the sitting and supine positions; six-minute walk distance; and locomotor ability.

Molecular analysis of holoprosencephaly in South America.

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts.

Clinical characteristics of alopecia areata in Down syndrome.

This study was undertaken to better understand clinical characteristics, environmental and physical events in Down syndrome (DS) and alopecia areata (AA). This cross-sectional study included 18 DS patients who were currently presenting or had presented AA. We evaluated gender, age, location and type of AA, presence of autoimmune disease or atopy, AA in first-degree relatives, and environmental, physical, and clinical intercurrences.

Severe intellectual disability, omphalocele, hypospadia and high blood pressure associated to a deletion at 2q22.1q22.3: case report.

Background: Recently, array-comparative genomic hybridization (aCGH) platforms have significantly improved the resolution of chromosomal analysis allowing the identification of genomic copy number gains and losses smaller than 5 Mb. Here we report on a young man with unexplained severe mental retardation, autism spectrum disorder, congenital malformations comprising hypospadia and omphalocele, and episodes of high blood pressure. An ~ 6 Mb interstitial deletion that includes the causative genes is identified by oligonucleotide-based aCGH.

[Family and religious traditions present in medical discourses by medical professionals about children with genetic diseases].

This study explores the influences of cultural traditions rooted in the tone of medical discourse at the Instituto Fernandes Figueira/ Fundação Oswaldo Cruz by physicians regarding children with genetic diseases involving malformations and mental retardation, as well as reflections upon the professional care for these children. Data were collected using oral interviews (in the form of conversational narratives) and were submitted to semiotic analysis. The results pointed to four main cultural traditions present in medical discourse: the norm, the reason, the family and the Jewish-Christian religiosity.

Spinal cord compression in young children with type VI mucopolysaccharidosis.

Spinal cord compression (SCC) is a known complication of mucopolysaccharidosis type VI (MPS VI) secondary to atlantoaxial subluxation, craniovertebral stenosis, posterior longitudinal ligament hypertrophy, or dural thickening. SCC is expected to occur in the natural history of the disease, regardless of enzyme replacement therapy (ERT), as intravenous enzyme does not cross the blood-brain barrier. We describe six MPS VI children with SCC, all diagnosed before 7years of age.

[Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts].

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified.

Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis.

In mucopolysaccharidosis VI, or Maroteaux-Lamy syndrome, deficiency of N-acetylgalactosamine 4-sulfatase leads to storage of glycosaminoglycans (GAGs) and MPS VI patients often develop spinal cord compression during the course of the disease due to GAG storage within the cervical meninges, requiring neurosurgical intervention, as intravenous (IV) enzyme replacement therapy (ERT) is not expected to cross the blood-brain barrier. We report the use of intrathecal (IT) recombinant human N-acetylgalactosamine 4-sulfatase (arylsulfatase B, or ASB) in a MPS VI child with spinal cord compression whose parents initially refused the surgical treatment. Assessments were performed at baseline, with clinical, neurological and biochemical evaluations, urodynamic studies and MRI of the CNS.

[Revisiting establishments of the etiology of Turner syndrome].

Based on an interview with José Carlos Cabral de Almeida, who took part in the investigative process, the article explores the research that culminated in the establishment of the genetic etiology of Turner syndrome. Cabral de Almeida also discusses other work that he sees as landmarks in the birth of cytogenetics and offers his current view of the development of clinicalgenetics and the important role played by cytogenetics, which affords more precise means of diagnosis, prognosis, and control ofgenetic disorders. In its conclusion, the article points to pioneer work that continues to impact medical genetics, especially the study of human chromosomes, still fundamental to the success of linking human genetics and disease processes.

Sonographic findings in a case of tetrasomy 9p associated with increased nuchal translucency and Dandy-Walker malformation.

We report a case of a 23-year-old pregnant woman, who underwent amniocentesis after ultrasound (US) examination in the first trimester which revealed a nuchal translucency thickness of 2.9 mm. Cytogenetic analysis revealed complete tetrasomy of the short arm of chromosome 9.

Cholelithiasis and biliary sludge in Downs syndrome patients.

Context And Objective: Although studies have demonstrated increased frequency of gallbladder abnormalities among Downs syndrome (DS) patients in some countries, there is only one paper on this subject in the Brazilian literature. The aim of this study was to demonstrate the prevalence, clinical characteristics and evolution of lithiasis and biliary sludge among DS patients in a maternity and childrens hospital in Rio de Janeiro.

Design And Setting: This was a cross-sectional study followed by a retrospective cohort study on all individuals with an ultrasound diagnosis of gallbladder abnormalities.

[Reliability of birth defect data on birth certificates of Rio de Janeiro, Brazil, 2004].

This study assessed the reliability of birth certificate data related to birth defects in Brazil's Live Birth Information System (SINASC). We selected 24 maternity hospitals in the Unified National Health System (SUS) and compared the reports of birth defects from birth certificates with medical records of mothers and live born infants in the city of Rio de Janeiro for the year 2004. After transposing the data to a specific form, the birth defects were coded by types and organ systems and compared to the SINASC data.

[Birth defects in Rio de Janeiro, Brazil: an evaluation through birth certificates (2000-2004)].

To evaluate the occurrence of birth defects in the city of Rio de Janeiro, Brazil, using the Live Birth Information System (SINASC), we performed a cross-sectional study on all live newborns with birth defects from January 1, 2000, to December 31, 2004. The variables referred to birth defects (presence and system affected), type of health service, mothers, gestations, live births, and deliveries. Prevalence of birth defects was 83/10,000 live births.

[Descriptive cross-sectional study of hearing-disabled children at the National Institute for Education of the Deaf in Rio de Janeiro, Brazil].

In Brazil, research is scarce on multiple disabilities and hearing disability in particular. Researchers began a pioneering study in 1992, evaluating students from public special education programs, currently focused on hearing disability. The authors evaluated 232 students ranging from 1 to 39 years of age (mean 10.

[Birth defects in Brazil and health care: proposals for public policies in clinical genetics].

The impact of birth defects in Brazil has increased steadily, indicating the need for specific health policy strategies. Despite the close relationship between clinical genetics and management of birth defects, less than 30% of the total demand is currently met by existing genetic services. The main problems are: difficult access to genetic services, services highly concentrated in the South and Southeast regions of the country, and insufficient laboratory support.

[Birth defects and health strategies in Brazil: an overview].

Birth defects have increased progressively in Brazil, shifting from the fifth to the second cause of infant mortality from 1980 to 2000, thus highlighting the need for specific health policy strategies. Some governmental and nongovernmental actions related to birth defects in Brazil include information services on teratogenic agents and inborn errors of metabolism, monitoring of birth defects, neonatal screening and treatment of some genetic diseases, and rubella immunization. In addition, flour fortification with folic acid for prevention of certain birth defects has begun recently.

Medical genetic services in the state of Rio de Janeiro, Brazil.

Rio de Janeiro is a state with close to 15 million inhabitants and approximately 250,000 births per year. The state counts nine clinical genetic units in public institutions, providing for 9,400 outpatient consultations yearly, which is insufficient to cover the estimated needs. Laboratory tests such as cytogenetics, inborn errors of metabolism and molecular studies are available on a limited basis.

[In contact with genetic diseases: norm and reason as cultural traditions in medical staff discourse at the Fernandes Figueira Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil].

This study aims to detect the influence of deeply rooted traditions on physicians' discursive constructions concerning children with genetic diseases involving malformations and mental retardation. It also aims to capture the reflections resulting from the professional care for (and contact with) these children. All the physicians work at the Fernandes Figueira Institute, Oswaldo Cruz Foundation, in Rio de Janeiro, Brazil.

Clinical, neuroimaging and cytogenetic findings in 20 patients with corpus callosum dysgenesis.

Twenty children with corpus callosum agenesis or hypoplasia were evaluated under a standardized investigation protocol. Psychomotor retardation, seizures, and craniofacial anomalies were the most prominent findings. There were three cases of chromosomal anomalies, all of them representing trisomy of chromosome 8.