¿Qué puede esconder el retraso global del desarrollo? A propósito de un caso de causa genética / What can Global Developmental Delay Conceal? Apropos of a Case with a Genetic Cause

Se presenta un niño de 6 años con antecedente de retraso del lenguaje que llevó a sus padres a realizar múltiples consultas. En un primer momento, su cuadro fue interpretado como parte de un retraso global del desarrollo. Posteriormente, el paciente presentó convulsiones y episodios de descompensación metabólica, comenzando desde entonces su seguimiento por los Servicios de neurología, genética y metabolismo. Finalmente, tras varios estudios complementarios, por medio de un exoma trío se arribó al diagnóstico de síndrome de microduplicación del cromosoma 7q11.23, lo que justifica tanto el retraso global de desarrollo del paciente como su clínica neurológica. (AU)

A six-year-old boy presents with a history of language delay that led his parents to make multiple consultations. At first, we interpreted his condition as part of a global developmental delay. Subsequently, the patient presented seizures and episodes of metabolic decompensation, and since then, he had to be followed up by neurology, genetics, and metabolism services. Finally, after several complementary studies, following a trio exome analysis, we diagnosed chromosome 7q11.23 microduplication syndrome, which explains his global developmental delay and neurological symptoms. (AU)

Application of copy number variation sequencing in patients with intellectual disability/developmental delay and autistic spectrum disorder / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD).@*METHODS@#Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation.@*RESULTS@#Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%).@*CONCLUSION@#Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.

Clinical and genetic analysis of a child with Schaaf-Yang syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with Schaaf-Yang syndrome (SYS).@*METHODS@#Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Sanger sequencing was used for family constellation verification, and bioinformatic analysis was performed for the candidate variant.@*RESULTS@#The child, a 1-year-and-9-month-old boy, had clinical manifestations of retarded growth, small penis, and unusual facies. Genetic testing revealed that the child has harbored a novel heterozygous variant of c.3078dupG (p.Leu1027Valfs*28) of the MAGEL2 gene. Sanger sequencing showed that neither parent of the child carried the same variant. The c.3078dupG(p.Leu1027Valfs*28) variant of the MAGEL2 gene has not been included in the databases of ESP, 1000 Genomes and ExAC. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was judged to be pathogenic.@*CONCLUSION@#The c.3078dupG (p.Leu1027Valfs*28) variant of the MAGEL2 gene probably underlay the SYS in this child, which has further expanded the spectrum of the MAGEL2 gene variants.

Genetic analysis of two children with developmental delay and intellectual disability / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of two patients with developmental delay and intellectual disability.@*METHODS@#Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions.@*RESULTS@#Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents.@*CONCLUSION@#The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.

Identification of a NONO gene variant in a child with congenital heart disease and global developmental delay / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD).@*METHODS@#A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children's Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c.457C>T (p.Arg153*) in the NONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant.@*CONCLUSION@#The c.457C>T (p.Arg153*) variant of the NONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.

Clinical characteristics and genetic analysis of two children with Autosomal dominant mental retardation type 21 due to variants of CTCF gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of two children with developmental delay.@*METHODS@#Two children who had presented at the Children's Hospital Affiliated to Shandong University on August 18, 2021 were enrolled as the study subjects. Clinical and laboratory examination, chromosomal karyotyping and high-throughput sequencing were carried out for both children.@*RESULTS@#Both children had a 46,XX karyotype. High-throughput sequencing showed that they have respectively carried a c.489delG (p.Q165Rfs*14) and a c.1157_1158delAT (p.Y386Cfs*22) frameshifting variant of the CTCF gene, both had a de novo origin and were unreported previously.@*CONCLUSION@#The CTCF gene variants probably underlay the development delay in the two children. Above discovery has enriched the mutational spectrum of the CTCF gene and has important implications for revealing the genotype-phenotype correlation for similar patients.

Clinical and genetic analysis of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH).@*METHODS@#Two children with MICPCH who were presented at the Henan Provincial People's Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and real-time quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated.@*RESULTS@#Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+PM2_Supporting).@*CONCLUSION@#The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.

De novo variant of CSNK2B causes Poirier-Bienvenu neurodevelopmental syndrome: two case report / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical characteristics and CSNK2B gene variant of 2 children with Poirier-Bienvenu neurodevelopmental syndrome, and to identify the possible pathogenic causes and provide evidence for clinical diagnosis.@*METHODS@#Two children with Poirier-Bienvenu neurodevelopmental syndrome were selected from West China Second University Hospital, Sichuan University. The clinical manifestations, laboratory examination and CSNK2B gene variant were analyzed.@*RESULTS@#The main manifestations of 2 children were epilepsy, motor or intellectual retardation. Whole exon sequencing showed that CSNK2B gene c. 291+4A>T heterozygous splicing variant was found in case one, and CSNK2B copy number variation(CNV) was lost in case two. Case one received no special treatment, followed up for 8+ months, seizures and motor development were improved; case two had recurrent seizures for 9+ years, and received levetiracetam and clonazepam antiepileptic treatment. No seizures have occurred for 2 years now, and a large number of epileptic discharges can still be seen in video electroencephalogram (VEEG) with slightly backward intelligence and language development.@*CONCLUSION@#Our study further proves that the pathogenic variant of CSNK2B is related to epilepsy with developmental disorder, and enrich is the CSNK2B gene variant spectrum. The pathogenesis of CSNK2B has great clinical heterogeneity, with great difference in severity of nervous system injury and different prognosis, and agenesis of corpus callosum may be one of its clinical phenotypes.

Clinical and genetic analysis of three children patients with Kleefstra syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of three children with unexplained developmental delay/intellectual disability (DD/ID).@*METHODS@#Peripheral blood samples were collected from the patients and subjected to chromosomal microarray analysis (CMA).@*RESULTS@#Patient 1 was found to harbor a 190 kb deletion at 9q34.3, which encompassed most of EHMT1 (OMIM 607001), the key gene for Kleefstra syndrome (OMIM 610253). Patients 2 and 3 were siblings. CMA showed that they have shared four chromosomal copy number variations (CNVs) including a deletion at 9q34.3 which spanned 154 kb and 149 kb, respectively, and encompassed the EHMT1 and CACNA1B (OMIM 601012) genes. The remaining 3 CNVs were predicted to be with no clinical significance.@*CONCLUSION@#Microdeletions at 9q33.4 probably underlay the pathogenesis of DD/ID in the three children, for which EHMT1 may be the key gene.

Clinical characteristics and gene analysis of GRIN2B gene related neurological developmental disorders in children / 中华儿科杂志

Objective: To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children. Methods: The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health and analyzed retrospectively. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results: Among 11 children 6 were boys and 5 were girls. Two of them were diagnosed with developmental and epileptic encephalopathy. The ages of seizures onset were 3 months and 9 months, respectively. Seizure types included epileptic spasm, tonic seizures, tonic spasm and focal seizures, and 1 patient also had startle attacks. EEG showed interictal multifocal epileptiform discharges. Both of them were added with more than 2 anti-seizure drugs, which were partially effective but could not control. They had moderate to severe mental and motor retardation. The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy, age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay, 2 cases had moderate and 2 cases had mild delay. Multi-focal epileptiform discharges were observed in 3 cases, no abnormality was found in 3 cases, and the remaining 3 cases did not undergo EEG examination. Ten cases underwent brain magnetic resonance imaging (MRI), 6 cases had nonspecific abnormalities and 4 cases were normal. Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients, 8 cases had missense variants and 1 case had nonsense variant, all of which were de novo and 3 of which were novel. Missense variants were found in 10 patients, among them 6 cases had severe developmental delay, 3 cases had moderate and 1 case had mild developmental delay, but the patient with nonsense variant showed mild developmental delay without epilepsy. Conclusions: The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epiletice episodes are refractory. Most of the patients with missense variants had severe developmental delay.

Experience and lessons on guiding and governing clinical applications of chromosome microarray analysis in the United States / 中华医学遗传学杂志

Chromosome microarray analysis (CMA) has become the first-tier testing for chromosomal abnormalities and copy number variations (CNV). This review described the clinical validation of CMA, the development and updating of technical standards and guidelines and their diagnostic impacts. The main focuses were on the development and updating of expert consensus, practice resources, and a series of technical standards and guidelines through systematic review of case series with CMA application in the literature. Expert consensus and practice resource supported the use of CMA as the first-tier testing for detecting chromosomal abnormalities and CNV in developmental and intellectual disabilities, multiple congenital anomalies and autism. The standards and guidelines have been applied to pre- and postnatal testing for constitutional CNV and tumor testing for acquired CNV. CMA has significantly improved the diagnostic yields but still needs to overcome its technical limitations and face challenges of new technologies. Guiding and governing CMA through expert consensus, practice resource, standards and guidelines in the United States has provided effective and safe diagnostic services to patients and their families, reliable diagnosis on related genetic diseases for clinical database and basic research, and references for clinical translation of new technologies.

Value of copy number variation analysis and chromosomal karyotyping for the diagnosis of children with intellectual disability/developmental delay / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variations (CNVs) and chromosomal karyotyping analysis for patients with intellectual disability/developmental delay (ID/DD).@*METHODS@#Chromosomal karyotype analysis was applied to 530 children diagnosed with ID/DD. Single nucleotide polymorphism array (SNP-array) was further applied for 120 children with unknown etiology.@*RESULTS@#Among the 530 children with ID/DD, 104 (19.62%) were detected with chromosomal abnormalities. For the 120 children analyzed by SNP-array, 44 (36.67%) were detected with CNVs, among which 20 were predicted as pathogenic, 6 as likely pathogenic, 10 as variants of unknown significance, 7 as likely benign,and 1 as loss of heterozygosity.@*CONCLUSION@#SNP-array can facilitate delineation of the etiology of patients with ID/DD, which may provide a basis for their prognosis, consultation and clinical intervention.

Molecular genetic analysis of a child with de novo 16p11.2 microdeletion / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring developmental delay, intelligent disability and language deficit.@*METHODS@#Peripheral blood samples of the child and her parents were collected for routine G-banding karyotyping analysis and single nucleotide polymorphism array (SNP array) detection. Amniotic fluid was also sampled from the mother for karyotyping analysis and SNP array detection.@*RESULTS@#No karyotypic abnormality was found with the child and her parents. SNP array showed that the child has carried a 761.4 kb microdeletion at 16p11.2, while her mother has carried a 444.4 kb microduplication at 15q13.3. Her father's result was negative. Further analysis showed that the 15q13.3 microduplication was inherited from her maternal grandfather who was phenotypically normal. Prenatal diagnosis showed that the fetus has inherited the15q13.3 microduplication from its mother.@*CONCLUSION@#The child has carried a de novo 16p11.2 microdeletion, which overlaps with 16p11.2 microdeletion syndrome region, in addition with similar clinical phenotypes. The 16p11.2 microdeletion probably underlies her abnormal phenotype.

Cytogenomic assessment of the diagnosis of 93 patients with developmental delay and multiple congenital abnormalities: The Brazilian experience

OBJECTIVE: The human genome contains several types of variations, such as copy number variations, that can generate specific clinical abnormalities. Different techniques are used to detect these changes, and obtaining an unequivocal diagnosis is important to understand the physiopathology of the diseases. The objective of this study was to assess the diagnostic capacity of multiplex ligation-dependent probe amplification and array techniques for etiologic diagnosis of syndromic patients. METHODS: We analyzed 93 patients with developmental delay and multiple congenital abnormalities using multiplex ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation-dependent probe amplification using different kits revealed several changes in approximately 33.3% of patients. The use of arrays with different platforms showed an approximately 53.75% detection rate for at least one pathogenic change and a 46.25% detection rate for patients with benign changes. A concomitant assessment of the two techniques showed an approximately 97.8% rate of concordance, although the results were not the same in all cases. In contrast with the array results, the MLPA technique detected ∼70.6% of pathogenic changes. CONCLUSION: The obtained results corroborated data reported in the literature, but the overall detection rate was higher than the rates previously reported, due in part to the criteria used to select patients. Although arrays are the most efficient tool for diagnosis, they are not always suitable as a first-line diagnostic approach because of their high cost for large-scale use in developing countries. Thus, clinical and laboratory interactions with skilled technicians are required to target patients for the most effective and beneficial molecular diagnosis.

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report / Insensibilidad al dolor en un niño con una deleción intersticial de novo del brazo largo del cromosoma 4

Terminal and interstitial deletions of the distal segment of the long arm of chromosome 4 (Cr4q del) are not common genetic disorders. The severity of the phenotype is correlated with the size of the deletion because small deletions have little clinical impact, whereas large deletions are usually associated with multiple congenital anomalies, postnatal growth failure, and moderate to severe intellectual disability. Alteration in pain tolerance has not been included among these features, also in case of large deletions. The purpose of this report is to document a case of a child affected by interstitial Cr4q del, expressing pain insensitivity as clinical feature not previously described. We also offer a discussion on genetic disorders featuring pain insensitivity/indifference. Case report. A Caucasian girl aged 12 came to our observation for a developmental delay with multiple congenital abnormalities and moderate intellectual disability (IQ 47). A de novo interstitial Cr4 del between band q31.3 and q32.2 (Cr4 del q31.3 to q32.2) was found. The child also expresses no evidence of pain perception to injures which normally evoke pain. Consequently, she is affected by severe disability caused by painless injuries and self-injurious behaviours, such as excessive self-rubbing and scratching. The neurological examination manifested high pain threshold with preserved tactile sensitivity. Conclusions. This is the first report of pain insensitivity in a patient with a specific genetic deletion involving the interstitial region of the distal long arm of Cr4. Moreover, this report could serve as a useful model to better understand mechanisms of pain perception and its modulation.

Why are mini-implants lost: The value of the implantation technique!

The use of mini-implants have made a major contribution to orthodontic treatment. Demand has aroused scientific curiosity about implant placement procedures and techniques. However, the reasons for instability have not yet been made totally clear. The aim of this article is to establish a relationship between implant placement technique and mini-implant success rates by means of examining the following hypotheses: 1) Sites of poor alveolar bone and little space between roots lead to inadequate implant placement; 2) Different sites require mini-implants of different sizes! Implant size should respect alveolar bone diameter; 3) Properly determining mini-implant placement site provides ease for implant placement and contributes to stability; 4) The more precise the lancing procedures, the better the implant placement technique; 5) Self-drilling does not mean higher pressures; 6) Knowing where implant placement should end decreases the risk of complications and mini-implant loss.

O uso de mini-implantes trouxe grandes contribuições ao tratamento ortodôntico. Essa demanda gerou curiosidade científica sobre os procedimentos e técnicas de implantação. Entretanto, instabilidades desses dispositivos ocorrem por motivos ainda não totalmente esclarecidos. Objetiva-se, com esse trabalho, relacionar a técnica de implantação com a taxa de sucesso dos mini-implantes por meio das seguintes hipóteses: 1) áreas com osso alveolar pobre e com pouco espaço inter-radicular levam à inadequada implantação; 2) diferentes áreas requerem distintos tamanhos de mini-implantes! O tamanho do implante deve acompanhar o diâmetro do osso alveolar; 3) a correta determinação do local em que será colocado o mini-implante facilita a instalação e contribui para a estabilidade; 4) quanto mais precisa for a lancetagem, melhor será a técnica de implantação; 5) autoperfuração não significa alta pressão; 6) saber onde finalizar a implantação diminui a incidência de complicações e de perda dos mini-implantes.

The First Korean Patient with Potocki-Shaffer Syndrome: A Rare Cause of Multiple Exostoses

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)x1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

The First Korean Patient with Potocki-Shaffer Syndrome: A Rare Cause of Multiple Exostoses

Potocki-Shaffer syndrome (PSS, OMIM #601224) is a rare contiguous gene deletion syndrome caused by haploinsufficiency of genes located on the 11p11.2p12. Affected individuals have a number of characteristic features including multiple exostoses, biparietal foramina, abnormalities of genitourinary system, hypotonia, developmental delay, and intellectual disability. We report here on the first Korean case of an 8-yr-old boy with PSS diagnosed by high resolution microarray. Initial evaluation was done at age 6 months because of a history of developmental delay, hypotonia, and dysmorphic face. Coronal craniosynostosis and enlarged parietal foramina were found on skull radiographs. At age 6 yr, he had severe global developmental delay. Multiple exostoses of long bones were detected during a radiological check-up. Based on the clinical and radiological features, PSS was highly suspected. Subsequently, chromosomal microarray analysis identified an 8.6 Mb deletion at 11p11.2 [arr 11p12p11.2 (Chr11:39,204,770-47,791,278)x1]. The patient continued rehabilitation therapy for profound developmental delay. The progression of multiple exostosis has being monitored. This case confirms and extends data on the genetic basis of PSS. In clinical and radiologic aspect, a patient with multiple exostoses accompanying with syndromic features, including craniofacial abnormalities and mental retardation, the diagnosis of PSS should be considered.

Impact of Intracoronal Dentin Treatment Prior to Bleaching on Bond Strength of Restorative Materials

Surface treatment of dentin before the bleaching procedure may affect its permeability and influence the bond strength of restorative materials. This study evaluated the influence of surface treatment before the bleaching on shear bond strength (SBT) of restorative materials to intracoronal dentin. Dentin slabs were subjected to surface treatment: no bleaching (control - CON), no surface treatment + bleaching (HP), 37% phosphoric acid + bleaching (PA) and Er:YAG laser + bleaching (L). After the bleaching procedure, specimens (n=10) were restored with: microhybrid composite resin (MH), flowable composite resin (F), and resin-modified glass-ionomer cement (RMGIC). The shear test was carried out. ANOVA and Tukey's test (α=0.05) showed significant difference for surface treatment and restorative materials (p<0.05). CON presented higher STB and was statistically different from HP (p<0.05). PA and L showed intermediate values and were statistically similar to CON and HP (p>0.05). STB for MH and F were higher than RMGIC (p<0.05), and did not differ from each other (p>0.05). The surface treatments with phosphoric acid and Er:YAG laser before the bleaching procedure provided shear bond strength at the same level of unbleached dentin and the composite resins presented superior bond strength to the intracoronal dentin.

O tratamento superficial da dentina previamente ao clareamento pode afetar a sua permeabilidade e influenciar a resistência de união de materiais restaurados. Este estudo avaliou a influência do tratamento superficial antes do clareamento na resistência ao cisalhamento (RC) de materiais restauradores à dentina intracoronária. Fragmentos de dentina foram submetidos ao tratamento de superfície: não clareadas (controle - CON), sem tratamento de superfície + clareamento (HP), ácido fosfórico 37% + clareamento (AF), e laser Er:YAG + clareamento (L). Após o procedimento clareador, os espécimes foram restaurados com (n=10): resina composta micro-híbrida (MH), resina composta fluida (F), e cimento de ionômero de vidro modificado por resina (CIVMR). O teste de cisalhamento foi realizado. ANOVA e teste de Tukey (α=0,05) mostraram diferença significante para tratamento superficial e material restaurador (p<0,05). O grupo controle apresentou maior resistência de união e foi estatisticamente diferente de HP (p<0,05). AF e L mostraram valores intermediários e foram similares ao CON e HP (p>0,05). A resistência de união para MH e F foi maior que CIVMR (p<0,05), e não diferiram entre si (p>0,05). O tratamento da superfície dentinária com ácido fosfórico e laser Er:YAG previamente ao clareamento promoveu resistência de união ao nível da dentina não clareada e a adesão à dentina intracoronária foi superior com as resinas compostas.

A endogamia explicaria a elevada prevalência de deficiências em populações do Nordeste brasileiro? / Could endogamy explain the higher prevalence of disabilities in the population of the Brazilian Northeast?

Apesar da inexatidão conceitual e de métodos de aferição, a OMS estima que cerca de 10% da população mundial apresente alguma forma de deficiência. Com a finalidade de investigar a prevalência e a etiologia das deficiências e verificar se elas estariam associadas à endogamia, foi realizado um estudo epidemiológico transversal com uso do método do informante envolvendo cinco municípios do Estado do Rio Grande do Norte, no Nordeste brasileiro; nos quais foram estimadas frequências de casamentos consanguíneos que variam de 9 a 32%. A prevalência média estimada para deficiências nos cinco municípios amostrados foi de 4,53%, obtida por meio de entrevistas envolvendo 37,87% de uma população de 39.054 habitantes. Em média, 25% dos casais consanguíneos e 12% dos não consanguíneos apresentaram um ou mais filhos com alguma deficiência. A elevada prevalência de pessoas com deficiência no Nordeste brasileiro pode ter associação com a manutenção da tradição de casamentos consanguíneos nessas populações e parte dessas deficiências pode ser causada por doenças genéticas.

Despite conceptual inaccuracies and methods of measurement, the WHO estimates that about 10% of the world population has some form of disability. In order to investigate the prevalence and etiology of disabilities and to evaluate if they could be associated with inbreeding, a cross-sectional epidemiological study was conducted using the informant method in five communities of the state Rio Grande do Norte in the Brazilian Northeast, in which consanguineous marriages frequencies varied between 9 and 32%. The average prevalence of disabilities in the five sampled communities was 4.53%, obtained by interviews that involved 37.87% of a population of 39,054 inhabitants. On average, 25% of consanguineous and 12% of non-consanguineous couples had one or more children with disabilities. The increased rate of individuals with disabilities in the Brazilian Northeast could be associated with the maintenance of the tradition of consanguineous marriages in these populations and some of these disabilities may be caused by genetic disorders.