Genetic testing and analysis of 2 cases of trisomy 11 mosaicism / 南方医科大学学报

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Monosomía 9p24 secundaria a translocación (2; 9) en dos pacientes no relacionadas / Monosomy 9p24 in two non-related patients as result of a translocation (2; 9)

En pacientes con malformaciones congénitas y retraso del desarrollo psicomotor, deben descartarse cromosomopatías. Las más frecuentes son las translocaciones recíprocas balanceadas, presentes en 1:500 recién nacidos vivos. Por lo general, los portadores tienen fenotipo normal, aunque, ocasionalmente, presentan infertilidad, abortos o hijos con malformaciones. La translocación balanceada entre los cromosomas 2 y 9 puede originar descendencia con monosomías y trisomías de estos cromosomas. La monosomía del brazo corto del cromosoma 9 puede presentarse con trigonocefalia, dismorfias faciales, anomalías genitales y retraso del desarrollo psicomotor. En este trabajo, se revisaron las alteraciones de los cromosomas 2 y/o 9 en los cariotipos realizados en nuestra Institución en 2005-2014. Se presentan dos pacientes con monosomía 9p asociada a translocación (2;9). Las pacientes comparten datos de monosomía 9p24-pter; la correlación genotipo-fenotipo es compleja por el tamaño de los segmentos involucrados. Se resalta la importancia del diagnóstico cromosómico para el asesoramiento genético.

In patients with malformations and delayed psychomotor development it is important to discard chromosomopathies. Balanced reciprocal translocations are the most frequent chromosomopathies present in 1:500 live newborns. In general, carriers have normal phenotype, but they may have infertility, abortions or children with congenital malformations. The reciprocal translocation between chromosomes 2 and 9 can lead to offspring with monosomies and trisomies of these chromosomes. Short arm monosomy of chromosome 9 may present delayed psychomotor development, trigonocephaly, facial dysmorphia and genital abnormalities. We reviewed GTG karyotype records from our Institution to identify cases with chromosomes 2 and/or 9 alterations from 2005 to 2014. We describe two cases with monosomy 9p secondary to a translocation between chromosomes 2 and 9. The patients share features of monosomy 9p24-pter, however the genotype-phenotype correlation is complex due to the extension of the involved segments. We emphasize the importance of chromosomal diagnosis to offer genetic assessment.

Síndrome de Pallister-Killian en una paciente mestiza mexicana: Reporte de caso / Paüister-KiUian syndrome in a Mexican mestizo patient: Case report

El síndrome de Pallister-Killian es una entidad poco frecuente causada por tetrasomía 12p en mosaico. Presenta facies tosca, alopecia frontotemporal, frente prominente, fisuras palpebrales oblicuas ascendentes, hipertelorismo ocular, ptosis palpebral, estrabismo, epicanto, puente nasal ancho, nariz corta, narinas antevertidas, filtrum largo, labio superior delgado e inferior prominente, pabellones auriculares con lóbulos gruesos y protruidos, cuello corto, pezones supernumerarios, manos anchas, braquidactilia, alteraciones en la pigmentación de la piel, cardiopatía congénita, discapacidad intelectual y crisis convulsivas. Su diagnóstico es complejo, ya que, en sangre periférica, el cariotipo suele ser normal. Se presenta el caso de una paciente mestiza mexicana de 4 años de edad con retraso en el desarrollo psicomotor y características fenotípicas que correspondieron a síndrome de Pallister-Killian. El cariotipo en fibroblastos de la biopsia de piel demostró mos47,XX,i(12)(p10)--#91;85--#93;/46,XX--#91;21--#93;. Un equipo multidisciplinario realiza el seguimiento con controles regulares por los departamentos de Neurología, Pediatría General y Genética Médica.

Pallister-Killian syndrome is caused by a tetrasomy 12p mosaicism and is characterized by facial dysmorphism, pigmentary skin anomalies, congenital heart defects, diaphragmatic hernia, epilepsy and mental retardation. The diagnosis is complex as the cytogenetic analysis in blood is usually normal, requiring karyotyping in other tissues, therefore the clinical suspicion is critical to guide the diagnostic tests and the patient requires an interdisciplinary clinical evaluation regarding the several manifestation of the syndrome. W e present the case of a Mexican mestizo female patient of 4 years of age referred by psychomotor delay and cleft palate; the clinical multidisciplinary evaluation demonstrated characteristics corresponding to the Pallister-Killian syndrome. The GTG banding karyotype analysis was normal, the skin fibroblast was mos47,XX,i(12)(p10)--#91;85--#93;/46,XX--#91;21--#93;. This case is an example of the importance of the clinical evaluation in order to establish a diagnosis that is a challenge for the clinical multidisciplinary team to offer medical management and genetic counseling.

Using Array-Based Comparative Genomic Hybridization to Diagnose Pallister-Killian Syndrome

Pallister-Killian syndrome (PKS) is a rare multisystem disorder characterized by isochromosome 12p and tissue-limited mosaic tetrasomy 12p. In this study, we diagnosed three pediatric patients who were suspicious of having PKS using array-based comparative genomic hybridization (array CGH) and FISH analyses performed on peripheral lymphocytes. Patients 1 and 2 presented with craniofacial dysmorphic features, hypotonia, and a developmental delay. Array CGH revealed two to three copies of 12p in patient 1 and three copies in patient 2. FISH analysis showed trisomy or tetrasomy 12p. Patient 3, who had clinical features comparable to those of patients 1 and 2, was diagnosed by using FISH analysis alone. Here, we report three patients with mosaic tetrasomy 12p. There have been only reported cases diagnosed by chromosome analysis and FISH analysis on skin fibroblast or amniotic fluid. To our knowledge, patient 1 was the first case diagnosed by using array CGH performed on peripheral lymphocytes in Korea.

De Novo San Luis Valley Syndrome-like der(8) Chromosome With a Concomitant dup(8p22) in a Mexican Girl

No abstract available.

Habilidades sociales: su importancia en mujeres con diagnóstico de Síndrome de Turner / Social skills: their importance for women diagnosed with Turner Syndrome / Habilidades sociais: sua importância em mulheres com diagnóstico de Síndrome de Turner

La Psicología Positiva postula la importancia de trabajar desde una mirada integradora de cada persona incluyendo sus fortalezas y debilidades. Esta mirada resulta importante al trabajar con poblaciones físicas, psicológicas y socialmente vulnerables. El Síndrome de Turner es un trastorno cromosómico determinado por la deleción del cromosoma X en el sexo femenino, siendo la talla y la disgenesia gonadal sus principales características físicas. Las mismas tienen un gran impacto en el desarrollo psicológico de esta población generando problemas en la capacidad de establecer relaciones sociales óptimas. El objetivo del presente trabajo es referenciar la importancia del desarrollo de habilidades sociales en el Síndrome de Turner, principalmente durante la niñez y la adolescencia, considerando que las mismas operan como un recurso salugénico para evitar trastornos mayores en la vida adulta.

Positive Psychology proposes the importance of working based on an integrated view of each person, including their strengths and weaknesses. This view is important for work with physically, psychologically and socially vulnerable populations. Turner Syndrome is a chromosomal disorder determined by the deletion of the X chromosome in females, with size and gonadal dysgenesis as the main physical characteristics.This syndrome has a strong impact on the psychological development of this population, creating problems among women with Turner Syndrome as it affects their ability to establish optimal relationships. The aim of this study is to highlight the importance of developing social skills for women with Turner Syndrome, particularly during childhood and adolescence, considering that these skills act as a healing method that prevents further disorders during adulthood.

A Psicologia Positiva postula a importância de trabalhar a partir de uma visão integradora de cada pessoa, incluindo suas forças e fraquezas. Esta percepção se resulta importante ao trabalhar com populações físicas, psicológicas e socialmente vulneráveis. A Síndrome de Turner é um transtorno cromossômico determinado pela eliminação do cromossomo X no sexo feminino, sendo a estatura e a gonadal dysgenesis suas principais características físicas. Essas têm um grande impacto no desenvolvimento psicológico desta população gerando problemas na capacidade de estabelecer relações sociais ideais. O objetivo do presente trabalho é mostrar a importância do desenvolvimento de habilidades sociais em relação à Síndrome de Turner, principalmente durante a infância e a adolescência, considerando que estas operam como um recurso salugênico para evitar transtornos maiores na vida adulta

Una revisión actualizada del síndrome de deleción (monosomía) 1p36 / An updated review of 1p36 deletion (monosomy) syndrome

El síndrome de monosomía 1p36 forma parte del grupo de enfermedades conocidas como «enfermedades de baja prevalencia¼ o «enfermedades raras¼. El objetivo del presente trabajo es revisar los hallazgos de los principales estudios realizados en niños diagnosticados con el síndrome de monosomía 1p36. El fenotipo del síndrome de deleción (monosomía) 1p36 delineado desde 1997 incluye rasgos craneofaciales dismórficos: fontanela anterior grande, cejas rectas, ojos hundidos, epicanto, raíz/puente nasal anchos, hipoplasia del tercio medio facial, orejas implantadas anormalmente, filtrum largo y barbilla puntiaguda; alteraciones neurológicas: convulsiones e hidrocefalia (en casos aislados); malformaciones cerebrales observadas en imágenes por resonancia magnética (IRM): ensanchamiento ventricular, ensanchamiento de espacios subaracnoideos, alteraciones morfológicas del cuerpo calloso, entre otras. La IRM evidencia en algunos pacientes atrofia cortical, retraso en la mielinización, áreas multifocales hiperintensas, leucomalacia periventricular y heterotopia periventricular. Estos pacientes cursan con discapacidad intelectual, retrasos en el desarrollo motor, de la comunicación, del lenguaje, en el área personal-social y en la conducta adaptativa. También se observan alteraciones en el sistema auditivo, visual, cardiaco, endocrino, genitourinario, dermatológico y esquelético. Conclusiones: Existen datos de aproximadamente 100 casos en el mundo desde 1981. Esta enfermedad rara es el síndrome más común de microdeleción subtelomérica. La técnica de hibridación in situ con fluorescencia y la técnica de hibridación genómica comparativa (array-CGH) son las que mejor permiten su diagnóstico. Por el momento no existe ningún tratamiento médico efectivo para esta enfermedad.

The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. Conclusions: Approximately 100 cases have been documented since 1981. This rare disease is the most common sub-telomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease.

Resultado de estudio prenatal invasivo para el diagnóstico de aneuploidía en el Hospital Sótero del Río / Results of an invasive prenatal study for the diagnosis of aneuploidy at Hospital Sótero del Río

ANTECEDENTES: Las aneuploidías y malformaciones congénitas son causa importante de morbi-mortalidad perinatal e infantil en Chile. OBJETIVO: Evaluar la realidad local del diagnóstico genético antenatal para mejorar el resultado perinatal. MÉTODOS: Estudio retrospectivo y descriptivo. Se realizó amniocentesis a embarazadas con indicación de estudio genético prenatal por sospecha ecográfica de alteraciones cromo-sómicas, entre octubre de 2010 y marzo de 2015, en el Hospital Sótero del Río. RESULTADOS: Los hallazgos ecográficos más frecuentes fueron: cardiopatías congénitas, malformaciones del sistema nervioso central y restricción de crecimiento fetal precoz. 164 pacientes aceptaron el estudio invasivo antenatal, obteniéndose resultados de 154. El promedio de edad materna y edad gestacional del examen fueron 30 años y 27+3 semanas, respectivamente. En embarazos con trisomía 21 y 13, el 71% de las pacientes tenía sobre 35 años. Un 31% de las muestras presentaron cariotipo anormal, siendo la más frecuente la trisomía 21 (14%), trisomía 18 (9%), monosomía X (4,5%) y trisomía 13 (2,6%). CONCLUSIÓN: El diagnóstico genético prenatal permite un adecuado manejo perinatal, coordinación apropiada entre las unidades de Obstetricia y Neonatología, y la preparación de las pacientes y sus familias para un pronóstico perinatal adverso.

BACKGROUND: Malformations and aneuploidy are a major cause of perinatal morbidity and mortality in Chile. Invasive techniques are offered to determine the fetal karyotype, when there is an abnormal finding in the ultrasound. AIMS: To assess the local situation of prenatal genetic diagnosis to improve the management of this population. METHODS: This is a retrospective and descriptive study of patients from october 2010 to march 2015, who had an amniocentesis for genetic testing due suspected fetal malformations or aneu-ploidy. RESULTS: The sonographic findings most frequently found were: congenital heart disease, malformations of the central nervous system and early growth restrictions. 164 patients agree to perform invasive prenatal genetic, obtaining 154 results. The average maternal age was 30 years and the mean gestational age at amniocentesis was 27+3 weeks. In trisomy 21 pregnancies, 71% of patients were higher than 35 years. 31% of the samples had abnormal karyotype: trisomy 21 (14%), trisomy 18 (9%), Turner's syndrome (4.5%) and trisomy 13 (3%). CONCLUSIONS: Prenatal genetic diagnosis allows appropriate perinatal management and contributes to prepare the patient and their families for an adverse perinatal outcome.

Prevalência das malformações congênitas identificadas em fetos com trissomia dos cromossomos 13, 18 e 21 / Prevalence of congenital abnormalities identified in fetuses with 13, 18 and 21 chromosomal trisomy

OBJETIVO: Descrever a prevalência das malformações encontradas nos fetos com trissomia dos cromossomos 13, 18 e 21, identificando as mais frequentes em cada condição. MÉTODOS: Estudo transversal retrospectivo, com análise dos casos de trissomias dos cromossomos 13, 18 e 21 que foram diagnosticados pelo cariótipo fetal obtido por amniocentese/cordocentese, entre outubro de 1994 e maio de 2014, em um Hospital de Ensino da região Sul do Brasil. Foram descritas as malformações identificadas no exame ultrassonográfico morfológico e, posteriormente, confirmadas em exames do recém-nascido e/ou por necropsia fetal. Os resultados foram analisados por meio do teste de Fisher e da análise de variância (ANOVA). O nível de significância empregado foi 5% (p=0,05). RESULTADOS: Em 840 exames realizados, foram diagnosticados 69 casos de trissomias; nove deles foram excluídos por desfecho ocorrido fora do Hospital de Clínicas de Porto Alegre ou prontuário incompleto, restando 60 casos (nove de trissomia do cromossomo 13, 26 do cromossomo 18 e 25 do cromossomo 21). As cardiopatias ocorreram, na maioria dos casos, nos três grupos; a comunicação interventricular foi mais prevalente, em 66,7% do grupo da trissomia 13. As anomalias gastrintestinais aconteceram mais no grupo da trissomia 18, principalmente a onfalocele (38,5%; p<0,01). As anomalias geniturinárias foram significativamente mais frequentes no grupo da trissomia 13 (pielectasia com 55,6% - p<0,01; genitália ambígua com 33,3% - p=0,01). Defeitos do sistema nervoso central foram identificados em todos os casos de trissomia 13. Fendas faciais foram mais prevalentes dentre os fetos com trissomia 13 (66,7%; p<0,01). Malformações nas mãos e nos pés tiveram diferenças estatísticas entre os grupos de trissomia. Os defeitos nas mãos ocorreram em 50% dos casos de trissomia 18 e em 44,4% dos casos de 13 (p<0,01); pé torto congênito foi mais comum no grupo da trissomia 18, descrito em 46,2% dos ...

PURPOSE: To describe the prevalence of malformations found in fetuses with trisomy of chromosomes 13, 18 and 21 by identifying the most frequent within each condition. METHODS: A retrospective cross-sectional study with the analysis of trisomy cases of chromosomes 13, 18 and 21 diagnosed through fetal karyotype obtained by amniocentesis/cordocentesis, between October 1994 and May 2014, at a Teaching Hospital in Brazil Southern Region. Malformations identified through morphological ultrasonography were described and, subsequently, confirmed in newborn examinations and/or fetal autopsy. The results were analyzed using Fisher's test and analysis of variance (ANOVA), with a 5% level of significance (p=0.05). RESULTS: Sixty-nine cases of trisomy were diagnosed among 840 exams; nine were excluded due to outcome outside Hospital de Clínicas de Porto Alegre or incomplete records, remaining 60 cases (nine cases of chromosome 13 trisomy, 26 of chromosome 18, and 25 of chromosome 21). In all three groups, heart disease occurred in most cases; the ventricular septal defect was more prevalent and occurred in 66.7% of the trisomy 13 group. Gastrointestinal abnormalities were more prevalent in the trisomy 18 group, especially omphalocele (38.5%; p<0.01). Genitourinary anomalies were more significantly frequent in the trisomy 13 group (pyelectasis, 55.6% - p<0.01; ambiguous genitalia, 33.3% - p=0.01). Central nervous system defects were identified in all cases of trisomy 13. Facial cracks were significantly more prevalent among fetuses with trisomy 13 (66.7%; p<0.01). Hand and feet malformations significantly differed among the trisomy groups. Hand defects occurred in 50% of trisomy 18 cases, and in 44.4% of all trisomy 13 cases (p<0.01); congenital clubfoot was more common in the trisomy 18 group, being detected in 46.2% of fetuses (p<0.01). The abnormalities were found in 50.9, 27.3 and 21.7% of trisomy 18, 13 and 21 cases respectively. ...

The Juscelino Kubitschek government and the Brazilian Malaria Control and Eradication Working Group: collaboration and conflicts in Brazilian and international health agenda, 1958-1961 / O governo JK e o Grupo de Trabalho de Controle e Erradicação da Malária no Brasil: encontros e desencontros nas agendas brasileira e internacional de saúde, 1958-1961

Malaria, a disease which was under control in the beginning of Juscelino Kubitschek government, became the most important endemic disease in 1958, when Brazil made a commitment with the World Health Organization to convert its control programs into eradication programs. For this purpose a Malaria Control and Eradication Group was set up under the leadership of the malaria specialist Mário Pinotti. Malaria would become an important bargaining chip in the context of the development policies of Kubitschek. This article focuses on path of the Malaria Control and Eradication Working Group in Brazil, in its varying relationships with the arguments and guidelines established at international level.

A malária, doença que estava controlada no início do governo de Juscelino Kubitschek, torna-se a mais importante endemia em 1958, quando o Brasil assumiu o compromisso com a Organização Mundial da Saúde de converter seus programas de controle em programas de erradicação. Para isso foi instalado um Grupo de Controle e Erradicação da Malária sob a direção do malariologista Mário Pinotti. A malária seria uma importante moeda de negociação no contexto da política de desenvolvimento de Kubitschek. Este artigo tem como foco a trajetória do Grupo de Trabalho de Controle e Erradicação da Malária no Brasil, em suas diferentes relações com as discussões e normativas travadas e estabelecidas em âmbito internacional.

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.

First Korean Case of SATB2-Associated 2q32-q33 Microdeletion Syndrome

No abstract available.

Molecular cytogenetic evaluation of chromosomal microdeletions: the experience of a public hospital in Southern Brazil

Introduction: During the past few decades, the number of diseases identified to be caused by chromosomal microdeletions has increased quickly, bringing a new and crucial role for cytogenetics on the diagnosis of these conditions. The purpose of this study was to identify and characterize chromosomal microdeletions associated with malformation syndromes and intellectual disability. Methods: We retrospectively evaluated a consecutive series of samples from a cohort of 598 subjects with clinical symptoms of a microdeletion syndrome, including the deletion of chromosomes 4p16.3, 5p15.2, 5q35, 7q11.23, 8q24.12, 15q11.2, 16p13.3, 17p13.3, 17p11.2,2, and 22q11.2, as investigated by fluorescence in situ hybridization (FISH). Array-based comparative genomic hybridization (array-CGH) was performed on 25 samples with microdeletions. Results: A total of 598 samples were evaluated from patients whose clinical phenotypes were most indicative of 22q11.2 deletion syndrome (29.10%), Prader-Willi syndrome (23.41%), Angelman syndrome (16.89%), and Williams-Beuren syndrome (14.72%). In 142 of the samples (23.75%), a chromosomal imbalance associated with phenotypic abnormalities was found. The deletion of 7q11.23 was the most frequent (8.03%), followed by del22q11.2 (5.68%) and del15q11.2 (5%). Conclusion: Our study reinforces the idea that the effort to improve the capacity to perform molecular cytogenetic investigations associated with a qualified clinical evaluation is crucial for the detection and precise characterization of submicroscopic chromosome deletions, bringing benefits to patients, relatives, and genetic counselors. It also contributes to the continuing education of cytogeneticists and to the knowledge of chromosomal rearrangements associated with genomic disorders.

Gestational, perinatal and family findings of patients with Patau syndrome / Hallazgos gestacionales, perinatales y familiares de pacientes con sindrome de Patau / Achados gestacionais, perinatais e familares de pacientes com sindrome de Patau

OBJECTIVE: To describe gestational, perinatal and family findings of patients with Patau syndrome (PS). METHODS: The study enrolled patients with PS consecutively evaluated during 38 years in a Clinical Genetics Service of a pediatric referral hospital in Southern Brazil. The clinical data and the results of cytogenetic analysis were collected from the medical records. For statistical analysis, the two-tailed Fisher's exact test and the chi-square test with Yates' correction were used, being significant p<0.05. RESULTS: The sample was composed of 27 patients, 63% were male, with a median age of nine days at the first evaluation. Full trisomy of chromosome 13 was the main cytogenetic finding (74%). Only six patients were submitted to obstetric ultrasound and none had prenatal diagnosis of PS. The patients' demographic characteristics, compared to born alive infants in the same Brazilian state showed a higher frequency of: mothers with 35 years old or more (37.5%); multiparous mothers (92.6%); vaginal delivery (77%); preterm birth (34.6%); birth weight <2500g (33.3%), and Apgar scores <7 in the 1st (75%) and in the 5th minute (42.9%). About half of them (53%) died during the first month of life. CONCLUSIONS: The understanding of the PS patients' gestational, perinatal and family findings has important implications, especially on the decision about the actions to be taken in relation to the management of these patients. .

OBJETIVO: Describir los hallazgos gestacionales, perinatales y familiares de pacientes con síndrome de Patau (SP) y compararlos con los de la población de nacidos vivos de la misma provincia, Rio Grande do Sul, presentes en la base de datos del Sistema Único de Salud (DATASUS). MÉTODOS: Esa investigación implicó a pacientes con diagnóstico de SP evaluados consecutivamente durante 38 años en el Servicio de Genética de un hospital pediátrico de referencia en el sur de Brasil. Los datos clínicos y los resultados del análisis citogenético fueron recogidos de los prontuarios médicos. Para el análisis estadístico, se utilizaron la prueba exacto de Fisher bicaudado y la prueba del chi cuadrado con corrección de Yates (p<0,05). RESULTADOS: La muestra fue compuesta por 27 pacientes, el 63% del sexo masculino, con mediana de edad en la primera evaluación de nueve días. La trisomía libre del cromosoma 13 fue el principal hallazgo citogenético (74%). Solamente seis pacientes presentaban relato de ultrasonografía obstétrica y ninguno tuvo diagnóstico pre-natal de SP. Al comparar los datos de esa muestra con los datos de nacidos vivos en la misma provincia, se observó que, para los pacientes con SP, hubo mayor frecuencia de madres con edad >35 años (37,5%); multíparas (92,6%); parto vaginal (77%); prematuridad (34,6%); peso al nacer <2.500g (33,3%) y escore de Apgar <7 en el 1º (75%) y 5º minuto (42,9%). Aproximadamente mitad de los pacientes (53%) murió en el primer mes de vida. CONCLUSIONES: El entendimiento de los hallazgos gestacionales, perinatales y familiares de SP lleva a importantes repercusiones, especialmente sobre la decisión respecto a las conductas a tomar en el manejo de esos pacientes. .

OBJETIVO: Descrever os achados gestacionais, perinatais e familiares de pacientes com síndrome de Patau (SP). MÉTODOS: Esta pesquisa envolveu pacientes com diagnóstico de SP avaliados consecutivamente durante 38 anos no Serviço de Genética de um hospital pediátrico de referência do sul do país. Os dados clínicos e os resultados da análise citogenética foram coletados dos prontuários médicos. Para a análise estatística, utilizaram-se o teste exato de Fisher bicaudado e o teste do qui-quadrado com correção de Yates (p<0,05). RESULTADOS: A amostra foi composta por 27 pacientes, 63% do sexo masculino, com mediana de idade na primeira avaliação de nove dias. A trissomia livre do cromossomo 13 foi o principal achado citogenético (74%). Somente seis pacientes apresentavam relato de ultrassom obstétrico e nenhum teve diagnóstico pré-natal de SP. Ao comparar os dados da presente amostra com os dados de nascidos vivos do mesmo estado, observou-se que, para os pacientes com SP, houve maior frequência de mães com idade >35 anos (37,5%); multíparas (92,6%); parto vaginal (77%), prematuridade (34,6%), peso ao nascer <2500g (33,3%) e escore de Apgar <7 no 1º (75%) e 5º minuto (42,9%). Cerca de metade dos pacientes (53%) morreu no primeiro mês de vida. CONCLUSÕES: O entendimento dos achados gestacionais, perinatais e familiares da SP leva a importantes repercussões, especialmente sobre a decisão quanto às condutas a serem tomadas no manejo desses pacientes. .

Another small supernumerary marker chromosome derived from chromosome 9 in a Klinefelter patient / Otro cromosoma marcador supernumerario pequeño derivado del cromosoma 9 en un paciente con el síndrome de Klinefelter

Marker chromosomes are very rare in Klinefelter patients and phenotypic findings are related to the affected chromosomal region. The phenotypic effects of small supernumerary marker chromosomes (sSMC) range from multiple malformations/mental retardation to no effect (ie a normal phenotype). This wide spectrum of phenotypes is due to the origin, structure and gene content of the marker chromosome. The first Klinefelter case with sSMC 9 was published by Liehr et al in 2005. The present case was referred for chromosomal analysis because of dysmorphic features, speech delay and mild mental retardation. Conventional cytogenetic analysis revealed the 47 XXY karyotype in 17 metaphases and the 48 XXY + marker karyotype in eight metaphases. Fluorescence in situ hybridization (FISH) analysis to identify the marker chromosome was performed using the LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe) and partial trisomy 9 mosaicism was confirmed in this patient. To our knowledge, this is the second case of Klinefelter syndrome with a small supernumerary marker chromosome derived from chromosome 9.

Los cromosomas marcadores son muy raros en los pacientes de Klinefelter, y los hallazgos fenotípicos se relacionan con la región cromosomática afectada. Los efectos fenotípicos de los cromosomas marcadores supernumerarios pequeños (sSMC) van desde el retraso mental y las malformaciones múltiples hasta la ausencia total de efectos (es decir, un fenotipo normal). Este amplio espectro de fenotipos se debe al origen, estructura y contenido del gen del cromosoma marcador. El primer caso de síntoma Klinefelter con sSMC 9 fue publicado por Liehr et al en 2005. El caso presente fue remitido para análisis cromosomático debido a rasgos dismórficos, retraso del habla, y retardo mental ligero. El análisis citogenético convencional reveló el cariotipo 47 XXY en 17 metafases y el cariotipo marcador 48 XXY+ en ocho metafases. El análisis mediante hibridación fluorescente in situ (FISH) para identificar el cromosoma marcador se realizó usando la sonda LSI p16 (9p21) Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe). Un mosaicismo de trisomía 9 parcial fue confirmado en este paciente. Hasta donde sabemos, éste es el segundo caso de síndrome de Klinefelter con un cromosoma marcador supernumerario pequeño derivado del cromosoma 9.

Síndrome de Phelan McDermid: descripción de cinco pacientes e informe del primer caso descripto en gemelas siamesas / Phelan McDermid Syndrome: five patients description and report on the frst case described in conjoined twins

El síndrome de Phelan McDermid es producido por una pérdida de material genético, en un cromosoma del par 22, a nivel de la banda q13.3. Se describieron cinco pacientes con deleción 22q13.3 para correlacionar genotipo-fenotipo y comunicar el primer caso descripto en gemelas siamesas. Se registraron antecedentes perinatales, psicomotores, conducta, lenguaje y presencia de dismorfas. Se realizó cariotipo e hibridación in situ fuorescente (FISH) para región crítica 22q13.3. Presentaron hipotonía, dismorfas menores, retraso madurativo y retraso o ausencia del lenguaje. Se confrmó deleción 22q13.3 en los cinco pacientes, encontrándose una deleción en dos casos y un anillo del cromosoma 22 en tres, siendo uno con línea pura, y las siamesas, con mosaicismo, con una línea celular normal. En pacientes con clínica sugestiva y fenotipo evocador de síndrome velo-cardio-facial, se debe realizar cariotipo y FISH para región crítica 22q11.2 con sonda control 22q13.3, para detectar la deleción del Síndrome de Phelan McDermid.

Phelan McDermid Syndrome is caused by the loss of genetic material in a chromosome from pair 22, at the band q13.3. We describe fve patients with deletion 22q13.3 in order to establish a genotype-phenotype association, and report the frst case described in conjoined twins. We analyzed the perinatal history, psychomotor behavior, language, and the presence of minor dysmorphism. Karyotypes and in situ hibridization (FISH) for critical region 22q13.3 were performed to all patients. There were hypotonia, developmental delay, and delay or absence of language. A 22q13.3 deletion was detected in all patients described, two cases had a deletion and the other three had a ring of chromosome 22, one in a pure cell line, while the twins presented mosaicism. Karyotype and FISH for 22q11.2 critical region should be performed, with 22q13.3 control probe to detect the deletion of Phelan McDermid syndrome in all patients with clinical phenotype suggestive and evocative of velo-cardio-facial syndrome.

Mosaic Ring Chromosome 6 in an Infant with Significant Patent Ductus Arteriosus and Multiple Congenital Anomalies

The clinical features of ring chromosome 6 include central nervous system anomalies, growth retardation, facial dysmorphism and other congenital anomalies. Ring chromosome 6 occurs rarely and manifests as various phenotypes. We report the case of mosaic ring chromosome 6 by conventional karyotyping in a 7-day-old male infant diagnosed with a large patent ductus arteriosus (PDA) with hypoplasia of aortic valve and aortic arch. These have not been previously reported with ring chromosome 6. He recovered from heart failure symptoms after ligation of the PDA. He showed infantile failure to thrive and delayed milestone in a follow-up evaluation. To the best of our knowledge, this is the first report of a Korean individual with ring chromosome 6 and hemodynamically significant PDA.

Características clínicas de uma amostra de pacientes com a síndrome do olho do gato / Clinical characteristics of a sample of patients with cat eye syndrome

OBJETIVO: A síndrome do olho do gato é considerada uma doença cromossômica rara e fenotipicamente bastante variável. O objetivo deste trabalho foi descrever as características clínicas de uma amostra de pacientes com a síndrome avaliada em nosso serviço. MÉTODOS: Foram analisados, retrospectivamente, seis pacientes com diagnóstico de síndrome do olho do gato. Todos eles apresentavam cariótipo com a presença de um cromossomo marcador adicional, inv dup(22)(pter->q11.2::q11.2->pter). Um deles, ainda, possuía mosacismo com uma linhagem com constituição cromossômica normal. A partir dos prontuários médicos foram coletados dados clínicos e de evolução dos pacientes. Para comparação entre as frequências encontradas em nosso estudo e a literatura foi utilizado o teste exato de Fisher (P<0,05). RESULTADOS: As principais anormalidades encontradas foram os apêndices/fossetas pré-auriculares e a imperfuração anal (ambas observadas em 83 por cento dos casos). O coloboma de íris, um achado importante da síndrome, foi verificado em dois casos (33 por cento). Cardiopatia congênita, por sua vez, foi observada em quatro pacientes (67 por cento), sendo o principal defeito a comunicação interatrial (75 por cento). Achados incomuns incluíram a microssomia hemifacial associada à microtia, além da atresia de vias biliares. Quanto à evolução clínica, apenas um dos pacientes foi a óbito, sendo que este ocorreu secundário a um quadro de quilotórax e sepse. CONCLUSÃO: O fenótipo observado na síndrome do olho do gato é bastante variável e pode se sobrepor àquele do espectro óculo-aurículo-vertebral. Apesar dos indivíduos apresentarem usualmente um bom prognóstico, incluindo do ponto de vista neurológico, acreditamos que todo paciente com a síndrome deveria ser precocemente avaliado quanto à presença de malformações cardíacas, biliares e anorretais. Isto evitaria possíveis complicações, incluindo o óbito.

OBJECTIVE: The cat eye syndrome is considered a rare chromosomal disease and a phenotypically quite variable condition. The objective of this study was to describe the clinical characteristics of a sample of patients with the syndrome evaluated in our Service. METHODS: Six patients with diagnosis of cat eye syndrome were retrospectively evaluated. All presented a karyotype with presence of an additional chromosome marker, inv dup(22)(pter->q11.2::q11.2->pter). One of them still had a mosaicism with a lineage with a normal chromosomal constitution. Clinical and evolution data were collected from their medical records. Fisher exact test (P<0.05) was used for comparison between the frequencies found in our study and literature. RESULTS: The main abnormalities found were preauricular skin tags/pits and imperforate anus (both observed in 83 percent of cases). Iris coloboma, an important feature of the syndrome was verified in 2 cases (33 percent). Congenital heart defect observed in 4 patients (67 percent), with the atrial septal defect (75 percent) as the most observed. Uncommon features included the hemifacial microsomia associated to microtia, besides biliary atresia. In relation to the evolution, only one of the patients died and this occurred secondary to quilothorax and sepsis. CONCLUSION: The phenotype observed in the cat eye syndrome is very variable and may overlap with that of oculo-auriculo-vertebral spectrum. Despite the good prognosis usually presented by the individuals, also from the neurological point of view, we believe that all patients with the syndrome should be evaluated as early as possible for presence of heart, biliary and anorectal malformations. This should avoid possible complications, including death.