Trisomy 13, home health-care and multidisciplinary approach: Case report / Trissomia 13, atendimento domiciliar e abordagem multidisciplinar: relato de caso

ABSTRACT Objective: To recognize and address Patau's syndrome, despite its rarity and associated low life expectancy, through the presentation of a case study of a 2-year-old patient receiving Home Care services. Case description: We present a female patient who defied the odds with a prolonged survival, possible due to Home Care. She was delivered via cesarean section at 31 weeks + 4 days due to restricted uterine growth. The mother, aged 36, had received proper prenatal care and was in good health. The diagnosis of Patau's syndrome was confirmed through karyotyping after birth. Despite the severe clinical nature of the case, the patient, now with two years old, receives specialized home-based care, supported by a tracheostomy and gastrostomy. A dedicated 24-hour nursing technician ensures continuous monitoring, and the patient benefits from regular medical check-ups, physiotherapy five times a week, weekly speech therapy sessions, monthly consultations with a nutritionist, and ongoing psychological support for her family members. Comments: This multidisciplinary approach has resulted in a slight motor response, highlighting the positive impact of comprehensive care on her overall well-being. The existence of a robust support network for families facing similar challenges is crucial, and a multidisciplinary care can effectively prevent complications associated with this impactful syndrome.

RESUMO Objetivo: Reconhecer e abordar a síndrome de Patau, apesar de sua raridade e da baixa expectativa de vida associada, por meio da apresentação de um estudo de caso de uma paciente de dois anos que recebe cuidados em casa por intermédio de serviços de home care. Descrição do caso: Apresentamos uma paciente do sexo feminino que desafiou as probabilidades, com sobrevivência prolongada devida, possivelmente, ao home care. Ela nasceu por cesariana, com 31 semanas + 4 dias, em razão da restrição do crescimento uterino. A mãe, de 36 anos, recebeu cuidados pré-natais adequados e gozava de boa saúde. O diagnóstico da síndrome de Patau foi confirmado por meio de cariótipo após o nascimento. Apesar da gravidade clínica do caso, a paciente, hoje com dois anos, recebe atendimento domiciliar especializado, apoiado por traqueostomia e gastrostomia. Um técnico de enfermagem dedicado 24 horas garante acompanhamento contínuo, e a paciente beneficia-se de check-ups médicos regulares, fisioterapia cinco vezes por semana, sessões semanais de fonoaudiologia, consultas mensais com nutricionista e apoio psicológico contínuo aos familiares. Comentários: Esta abordagem multidisciplinar resultou em melhora motora discreta, destacando o impacto positivo do cuidado integral no seu bem-estar geral. A existência de uma rede robusta de apoio às famílias que enfrentam desafios semelhantes é crucial, e um cuidado multidisciplinar pode prevenir eficazmente as complicações associadas a esta impactante síndrome.

Impact of orthodontic treatment with aligners on the oral health-related quality of life of patients with trisomy 21.

OBJECTIVE: To assess the impact of treatment with orthodontic aligners (OA) on oral health-related quality of life (OHRQoL) in patients with trisomy 21 (T21) compared to non-syndromic patients. MATERIALS AND METHODS: The sample consisted of 30 patients, both sexes, aged between 11 and 35 years, divided into two groups: T21 (n = 10, patients with T21, treated prospectively) and CONTROL (n = 20, control group, non-syndromic patients, from the Orthodontic Laboratory of UNOPAR). In both groups, patients were treated with Invisalign orthodontic aligners (Align Technology), following the same treatment parameters. Participants, assisted by their caregivers, when necessary, answered Oral Health Impact Profile (OHIP-14) instrument and the patient's guardians answered the Oral Health Scale for People with Down's syndrome (OHDS) instrument, before (T0) and after 30 (T1), 180 (T2), and 365 (T3) days from the start of treatment. Friedman tests with Bonferroni correction and Mann-Whitney tests were used (p < .05). RESULTS: For the OHDS instrument, it was observed that for the eating and communication domains and an overall score, the treatment with OA positively impacted the lives of T21 patients (p < .05). Regarding the OHIP-14 instrument, the intragroup evaluation showed that in the CONTROL group, there was no significant difference between the evaluated times; while for the T21 group, there was a significant positive impact (p < .05). CONCLUSION: The results showed that the treatment with aligners positively impacted the OHRQoL of T21 patients, and these results were perceived by caregivers, mainly in relation to issues related to eating and communication.

Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos / Immune compromise in patients with Down syndrome. A case series

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

Laryngotracheomalacia in a Patient with Mosaic Trisomy 8.

Mosaic trisomy 8 is a condition characterized by a great phenotypic and cytogenetic variability whose incidence ranges around 1 in 25,000 to 50,000 live births. Here, we report a mosaic trisomy 8 patient presenting laryngotracheomalacia, an uncommon finding, analyzing its possible role over morbidity, and mortality. The patient was a boy who, after birth, had tachypnea and paleness. He presented periods of respiratory dysfunction with need of ventilatory support. Respiratory syncytial virus test was positive. Naso fibrobronchoscopy showed moderate laryngotracheomalacia. He also had recurrent episodes of pneumonia and difficulty in withdrawing continuous positive airway pressure. The patient also presented leucoma, abnormal and low-set ears, pectus excavatum, clenched fists with overlapping fingers, cryptorchidism, clubfeet, and deep longitudinal plantar creases. G-bands by Trypsin using giemsa (GTG-banding) karyotype from a peripheral blood sample revealed a mosaic trisomy 8: mos 47,XY, + 8[15]/46,XY[7]. At 4 months, the patient developed respiratory failure, and a chest computed tomography scan showed areas of atelectasis and gross fibroatelectatic striae. He ended up presenting clinical worsening and died at 4 months and 8 days. In our literature review, we found some reports describing patients with mosaic trisomy 8 and laryngotracheomalacia. However, we cannot rule out the possibility that this association could be casual, since laryngotracheomalacia is a relatively common finding in children. Therefore, more studies are still necessary to understand the possible relation between both conditions and the role of laryngotracheomalacia over morbidity and prognosis of mosaic trisomy 8 patients.

Birth after low-level +20 Aneuploid Mosaic Embryo Transfer: A Case Report.

OBJECTIVE: Recently, it has been discussed whether or not mosaic embryo transfers should be performed since they might result in viable pregnancies, although they often end up being discarded. We report a case of successful pregnancy, after a mosaic embryo transfer from an in vitro matured egg and frozen PESA sperm. CASE DESCRIPTION: Tests performed on a female aged 40 years and a male aged 37 years seeking fertility treatment found she had an adequate ovarian reserve and patent fallopian tubes. He had a history of cryptorchidism and inguinal hernia repair. The spermogram showed azoospermia, and testicular ultrasound showed an atrophic left testicle and a normal right testis. The vas deferens was palpated during physical examination. Intracytoplasmic sperm injection with percutaneous epididymal sperm aspiration (PESA) was indicated. Two cycles of IVF after controlled ovarian stimulation with follitropin delta was performed. In the first cycle, seven mature eggs were inseminated, two fertilized normally, resulting in one blastocyst biopsied and analyzed by NGS with complex aneuploid results. In the second cycle, frozen sperm from PESA was used. Three eggs were inseminated on the day of the procedure (resulting in 2 blastocysts), and three in vitro matured eggs were inseminated after 24 hours (resulting in 1 blastocyst). NGS analysis showed two complex aneuploid embryos and one 40% low-level trisomy 20 aneuploid mosaicism (+20) for the post 24-hour embryo. A mosaic embryo transfer was performed, resulting in clinical pregnancy and birth of a healthy baby girl with a normal blood karyotype. DISCUSSION: Mosaic embryo transfer is a topic for discussion. Certain levels of mosaicism do not seem to pose risks to the development of the fetus.

Contemporary Trends in Cardiac Surgical Care for Trisomy 13 and 18 Patients Admitted to Hospitals in the United States.

OBJECTIVE: To assess rates of cardiac surgery and the clinical and demographic features that influence surgical vs nonsurgical treatment of congenital heart disease (CHD) in patients with trisomy 13 (T13) and trisomy 18 (T18) in the United States. STUDY DESIGN: A retrospective study was performed using the Pediatric Health Information System. All hospital admissions of children (<18 years of age) with T13 and T18 in the United States were identified from 2003 through 2022. International Classifications of Disease (ICD) codes were used to identify presence of CHD, extracardiac comorbidities/malformations, and performance of cardiac surgery. RESULTS: Seven thousand one hundred thirteen patients were identified. CHD was present in 62% (1625/2610) of patients with T13 and 73% (3288/4503) of patients with T18. The most common CHD morphologies were isolated atrial/ventricular septal defects (T13 40%, T18 42%) and aortic hypoplasia/coarctation (T13 21%, T18 23%). Single-ventricle morphologies comprised 6% (100/1625) of the T13 and 5% (167/3288) of the T18 CHD cohorts. Surgery was performed in 12% of patients with T13 plus CHD and 17% of patients with T18 plus CHD. For all cardiac diagnoses, <50% of patients received surgery. Nonsurgical patients were more likely to be born prematurely (P < .05 for T13 and T18). The number of extracardiac comorbidities was similar between surgical/nonsurgical patients with T13 (median 2 vs 2, P = .215) and greater in surgical vs nonsurgical patients with T18 (median 3 vs 2, P < .001). Hospital mortality was <10% for both surgical cohorts. CONCLUSIONS: Patients with T13 or T18 and CHD receive surgical palliation, but at a low prevalence (≤17%) nationally. Given operative mortality <10%, opportunity exists perhaps for quality improvement in the performance of cardiac surgery for these vulnerable patient populations.

Enhancing Speech Rehabilitation in a Young Adult with Trisomy 21: Integrating Transcranial Direct Current Stimulation (tDCS) with Rapid Syllable Transition Training for Apraxia of Speech.

Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed toward examining post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and Trisomy 21 (T21, Down syndrome). This N-of-1 randomized trial examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) over 10 sessions of anodal tDCS (1.5 mA, 25 cm) over Broca's area with the cathode over the contralateral region was compared to 10 sessions of sham-tDCS and four control sessions in a 20-year-old male individual with T21 presenting moderate-severe childhood apraxia of speech (CAS). The accuracy for NSW production progressively improved (gain of 40%) under tDCS (sham-tDCS and control sessions showed < 20% gain). A decrease in speech severity from moderate-severe to mild-moderate indicated transfer effects in speech production. Speech accuracy under tDCS was correlated with Wernicke's area activation (P3 current source density), which in turn was correlated with the activation of the left supramarginal gyrus and the Sylvian parietal-temporal junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated speech sound acquisition in a young adult with T21 and CAS, possibly through activating brain regions required for phonological working memory.

Immune compromise in patients with Down syndrome. A case series. / Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patients developed agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Association of Down syndrome with periodontal diseases: Systematic review and meta-analysis.

BACKGROUND: Down syndrome (DS) is distinguished by cognitive disability, a concave profile, and systemic complications. Oral diseases have been reported to be common in DS patients. OBJECTIVE: To investigate the association between DS and periodontal diseases. METHODS: Two independent reviewers searched six bibliographic databases up to January 2023 and used additional search methods to identify published studies on gingivitis or periodontitis in people with and without DS. Meta-analysis, risk of bias, sensibility analysis, publication bias, and evidence grading were all carried out. RESULTS: Twenty-six studies were included for analysis. There was a tendency for increased plaque accumulation, periodontal probing, periodontal attachment level, bleeding on probing and indices in DS individuals. Meta-analysis of 11 studies showed a significant association between DS and periodontitis (OR 3.93; 95% CI 1.81-8.53). Probing depth was significantly high in individuals with DS as compared to controls (mean difference 0.40 mm; 95% CI 0.09-0.70). Gingivitis was significantly associated (OR 1.93; 95% CI 1.09-3.41) with DS in four studies. The evidence was classified as 'moderate certainty'. CONCLUSION: Medium/low-quality studies demonstrate that Down syndrome is strongly associated with periodontitis and moderately associated with gingivitis.

Enhancing understanding of SARS-CoV-2 infection among individuals with Down syndrome: An integrative review

ABSTRACT BACKGROUND: Down syndrome (DS) is a non-rare genetic condition that affects approximately 1 in every 800 live births worldwide. Further, it is associated with comorbidities, anatomical alterations of the respiratory tract, and immunological dysfunctions that make individuals more susceptible to respiratory infections. OBJECTIVE: To systematize the current scientific knowledge about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among individuals with DS. DESIGN AND SETTING: This integrative review was conducted at the Universidade Federal de São Carlos, São Paulo, Brazil. METHODS: This review was conducted in the following databases: the Virtual Health Library (Biblioteca Virtual em Saúde, BVS), PubMed, and Web of Science, using MeSH descriptors. The search included English or Portuguese studies published between January 1, 2020, and October 14, 2022. RESULTS: A total of 55 articles from 24 countries were selected, comprising 21 case-control or cohort studies, 23 case reports or series, and 11 narrative reviews or opinion studies. The articles were grouped into five categories: previous comorbidities, coronavirus disease 2019 (COVID-19) clinical features and evolution, cytokine storm and interleukins, living in institutions as a risk factor, and behavioral actions as a protective factor against SARS-CoV-2 infection. CONCLUSION: Individuals with DS are more susceptible to COVID-19 infection due to variables such as previous comorbidities, immunological factors, and their habitable environments. These aspects confer a higher risk of infection and an unfavorable clinical course. The precise pathways involved in the pathophysiology of COVID-19 in individuals with DS are not clear, thus requiring further studies. SYSTEMATIC REVIEW REGISTRATION: The Open Science Framework registered the research protocol (https://osf.io/jyb97/).

Patau and Edwards Syndromes in a University Hospital: beyond palliative care / Síndrome de Edwards e Patau em um hospital universitário: além do paliativo

ABSTRACT Objective: To describe the newborn population with Patau (T13) and Edwards Syndrome (T18) with congenital heart diseases that stayed in the Intensive Care Unit (ICU) of a quaternary care hospital complex, regarding surgical and non-surgical medical procedures, palliative care, and outcomes. Methods: Descriptive case series conducted from January/2014 to December/2018 through analysis of records of patients with positive karyotype for T13 or T18 who stayed in the ICU of a quaternary hospital. Descriptive statistics analysis was applied. Results: 33 records of eligible patients were identified: 27 with T18 (82%), and 6 T13 (18%); 64% female and 36% male. Eight were preterm infants with gestational age between 30-36 weeks (24%), and only 4 among the 33 infants had a birth weight >2500 g (12%). Four patients underwent heart surgery and one of them died. Intrahospital mortality was 83% for T13, and 59% for T18. The majority had other malformations and underwent other surgical procedures. Palliative care was offered to 54% of the patients. The median hospitalization time for T18 and T13 was 29 days (range: 2-304) and 25 days (13-58), respectively. Conclusions: Patients with T13 and T18 have high morbidity and mortality, and long hospital and ICU stays. Multicentric studies are needed to allow the analysis of important aspects for creating protocols that, seeking therapeutic proportionality, may bring better quality of life for patients and their families.

RESUMO Objetivo: Descrever a população de recém-nascidos com síndrome de Patau (T13) e Edwards (T18) portadores de cardiopatias congênitas, que permaneceram em Unidades de Terapia Intensiva (UTI) de um complexo hospitalar quaternário, com relação a conduta cirúrgica ou não, cuidados paliativos e seus desfechos. Métodos: Série de casos de pacientes internados entre janeiro de 2014 a dezembro de 2018, com análise dos prontuários de portadores de T13 ou T18 que permaneceram internados em UTI que recebem neonatos nesse hospital quaternário. Utilizou-se análise estatística descritiva. Resultados: Foram identificados 33 prontuários para análise — 27 T18 (81,8%) e seis T13 (18,2%); 64% do sexo feminino e 36% do sexo masculino. Oito foram prematuros, nascidos com 30 a 36 semanas (24,2%), e apenas quatro nasceram com mais de 2500 g (12,1%). Quatro pacientes foram submetidos a cirurgia cardíaca e um deles foi a óbito. A mortalidade intra-hospitalar foi de 83% para T13 e 59% para T18. A maioria apresentava outras malformações e foi submetida a outras cirurgias. Cuidados paliativos foram oferecidos a 54% dos pacientes. A mediana do tempo de hospitalização para T18 e T13 foi respectivamente de 29 dias (variação: 2-304) e 25 dias (13-58). Conclusões: Pacientes com T13 e T18 cursam com alta morbimortalidade e longa permanência hospitalar em UTI. São necessários estudos multicêntricos para melhor análise de aspectos importantes para a criação de protocolos que, buscando proporcionalidade terapêutica, tragam melhor qualidade de vida para os pacientes e suas famílias.

Holoprosencefalia alobar. reporte de caso / Holoprosencephaly alobar. Case Report

Desde el advenimiento de la ecografía obstétrica y estudios invasivos además genéticos fetales han ayudado en la detección antenatal de anormalidades congénitas siendo uno de los objetivos básicos de la vigilancia fetal anteparto. La combinación de ambas técnicas ofrece, hoy en día un abordaje completo en términos de diagnóstico prenatal. Se cree que muchos trastornos del desarrollo surgen de factores de riesgos genéticos y ambientales. Uno de estos es la holoprosencefalia, sirve como modelo para comprender diversas formas de etiología multifactorial. El análisis genómico, la epidemiología y estudios mecánicos de modelos animales han revelado que factores de riesgo interactúan para producir resultados de desarrollo adversos. La holoprosencefalia es consecuencia de factores genéticos y/o ambientales que interrumpen la especificación de la línea media del prosencéfalo en formación. Estas alteraciones dan lugar a una amplia gama de consecuencias fenotípicas para el cerebro y la cara del nuevo ser humano en formación. Son comunes en 1 de 250 fetos humanos, pero el 97% no sobrevive al nacimiento. La patogenia molecular precisa de la holoprosencefalia sigue siendo desconocida. Aquí, describimos nuestra comprensión de los principales factores impulsores que conducen a patologías de holoproscencefalia y elaboramos nuestro enfoque de genómica integrada multifactorial. Las tecnologías genómicas proporcionan una visión sin precedentes de la variación asociada a la enfermedad. A continuación, se describe un caso de diagnóstico prenatal de trisomía 13 y holoprosencefalia. En éste, se logró establecer un diagnóstico antenatal anatómico y genético preciso.

Since the advent of obstetric ultrasound and invasive studies, fetal genetics have helped in the antenatal detection of congenital abnormalities, being one of the basic objectives of antepartum fetal surveillance. The combination of both techniques currently offers a complete approach in terms of prenatal diagnosis. Many developmental disorders are thought to arise from genetic and environmental risk factors. One of these is holoprosencephaly, which serves as a model for understanding various forms of multifactorial etiology. Genomic analysis, epidemiology, and mechanistic studies of animal models have revealed that risk factors interact to produce adverse developmental outcomes. Holoprosencephaly results from genetic and/or environmental factors that disrupt the specification of the midline of the forming forebrain. These alterations result in a wide range of phenotypic consequences for the brain and face of the newly developing human being. They are common in 1 in 250 human fetuses, but 97% do not survive birth. The precise molecular pathogenesis of holoprosencephaly remains unknown. Here, we describe our understanding of the main drivers leading to holoproscencephaly pathologies and elaborate on our multifactorial integrated genomics approach. Genomic technologies provide unprecedented insight into disease-associated variation. A case of prenatal diagnosis of trisomy 13 and holoprosencephaly is described below. In this study, it was possible to establish an accurate anatomical and genetic antenatal diagnosis.

Prevalence and clinical characterization of oral clefts in patients with chromosome trisomy 18 / Prevalência e caracterização clínica de fendas orais em pacientes com trissomia do cromossomo 18

ABSTRACT Objective: To verify the prevalence and perform the clinical characterization of oral clefts in a sample of patients with trisomy of chromosome 18 in Southern Brazil. Methods: This was a retrospective cross-sectional study, performed in a reference clinical genetic service in Southern Brazil. The initial sample consisted of 77 patients diagnosed in the neonatal period with trisomy 18 treated at the Clinical Genetics Service of a referral hospital at Federal University of Health Sciences of Porto Alegre (UFCSPA). The patients' diagnosis was confirmed by karyotype and care was provided during their stay in the intensive care unit (ICU) of the hospital that is a reference in Southern Brazil for care for malformed patients. The period covered was from 1975 to 2020. Results: During the study period, 77 patients diagnosed with trisomy 18 were treated, most of them in the ICU. Of these, 13 individuals were excluded due to incomplete data. The final sample consisted of 64 patients with an average age of 2.4 years of life, ranging from one day to 16 years old, the majority of whom were female. Regarding face dysmorphisms identified in the sample, three (4,68%) patients had cleft lip and two (3,11%) had cleft lip and palate. Conclusions: This study contributed to the recognition of the characteristics and prevalence of oral clefts in individuals with trisomy 18 in a sample of patients from Southern Brazil. In addition, we described the clinical alterations found in patients with oral clefts, as well as other associated comorbidities, such as cardiac, neurological and pulmonary comorbidities, as well as cranial and facial dysmorphisms.

RESUMO Objetivo: Verificar a prevalência e realizar a caracterização clínica das fissuras orais em uma amostra de pacientes com trissomia do cromossomo 18 no sul do Brasil. Métodos: Este foi um estudo transversal retrospectivo, realizado em um serviço de referência em genética clínica do sul do Brasil. A amostra inicial foi composta de 77 pacientes com diagnóstico no período neonatal de trissomia 18 atendidos no Serviço de Genética Clínica da Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA). O diagnóstico dos pacientes foi confirmado por cariótipo e os atendimentos foram realizados durante sua internação na unidade de terapia intensiva (UTI) de hospital de referência no sul do Brasil para atendimento em pacientes malformados. O período abrangido foi de 1975 a 2020. Resultados: Durante o período do estudo foram atendidos, a maioria na UTI do hospital, 77 pacientes com diagnóstico de trissomia do cromossomo 18. Destes, 13 indivíduos foram excluídos por apresentarem dados incompletos. A amostra final foi de 64 pacientes, com idade média de 2,4 anos de vida, variando de um dia de vida a 16 anos, a maioria do sexo feminino. Com relação aos dismorfismos faciais identificados na amostra, três (4,68%) pacientes apresentavam fissuras labiais e dois (3,11%) fissuras labiopalatinas. Conclusões: Este estudo trouxe como contribuições o reconhecimento das características e a prevalência das fendas orais nos indivíduos com trissomia do cromossomo 18 em uma amostra de pacientes do sul do Brasil. Além disso, descrevemos as alterações clínicas encontradas em pacientes com fissuras orais, bem como outras comorbidades associadas, como comorbidades cardíacas, neurológicas e pulmonares, além de dismorfismos cranianos e faciais.

Occurrence of mosaic trisomy 22 and pericentric inversion of chromosome 9 in a patient with a good prognosis.

Complete trisomy 22 is a rare chromosomal condition that is incompatible with life. However, mosaic trisomy 22 usually has prolonged survival compatibility and may present a good prognosis depending on the tissues affected. Herein, we described a male patient with the occurrence of mosaic trisomy 22 associated with the inversion of chromosome 9, with karyotype 47, XY, inv (9) (p11q13), + 22 [5] / 46, XY, inv(9) (p11q13) [45] and arr 22q11.1 ~ q13.33(16,417008-51,219,009)x2 ~ 3. It is not possible to infer, in general, the clinical characteristics associated with mosaic trisomy 22. However, the patient presented common clinical features observed in reported cases (in parentheses the percentage observed comparing all reported cases): facial dysmorphia (100%), delay in motor development/growth (82%), cardiac abnormalities (73%), ear abnormalities (55%) and facial and/or body asymmetry (55%), in addition to hypotonia, skin spots, hypoplastic nails. Given the survival and quality of life associated with multidisciplinary treatment, it can be concluded that the patient has a good prognosis. Conclusively, we're presenting the occurrence of mosaic trisomy 22 and chromosome 9 inversion in the patient with favorable prognosis. Thus, this study proposed a guide which should be inserted in databases of rare genetic conditions to help genetic counselors define mosaic trisomy 22 diagnosis.

Unusual Trisomy X Phenotype Associated with a Concurrent Heterozygous 16p11.2 Deletion: Importance of an Integral Approach for Proper Diagnosis.

Trisomy X is the most frequent sex chromosome anomaly in women, but it is often underdiagnosed postnatally because most patients do not show any clinical manifestation. It is estimated that only 10% of patients with trisomy X are diagnosed by clinical findings. Thus, it has been proposed that the clinical spectrum is not yet fully delimited, and additional uncommon or atypical clinical manifestations could be related to this entity. The present report describes a female carrying trisomy X but presenting atypical manifestations, including severe intellectual disability, short stature, thymus hypoplasia, and congenital hypothyroidism (CH). These clinical findings were initially attributed to trisomy X. However, chromosome microarray analysis (CMA) subsequently revealed that the patient also bears a heterozygous 304-kb deletion at 16p11.2. This pathogenic copy-number variant (CNV) encompasses 13 genes, including TUFM. Some authors recommend that when a phenotype differs from that described for an identified microdeletion, the presence of pathogenic variants in the non-deleted allele should be considered to assess for an autosomal recessive disorder; thus, we used a panel of 697 genes to rule out a pathogenic variant in the non-deleted TUFM allele. We discuss the possible phenotypic modifications that might be related to an additional CNV in individuals with sex chromosome aneuploidy (SCA), as seen in our patient. The presence of karyotype-demonstrated trisomy X and CMA-identified 16p11.2 deletion highlights the importance of always correlating a patient's clinical phenotype with the results of genetic studies. When the phenotype includes unusual manifestations and/or exhibits discrepancies with that described in the literature, as exemplified by our patient, a more extensive analysis should be undertaken to enable a correct diagnosis that will support proper management, genetic counseling, and medical follow-up.

Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies.

Introduction: The pure interstitial trisomy 11q11q23.2 is an uncommon genomic disorder associated with nonrecurrent intrachromosomal duplications. The phenotype is characterized by intellectual disability and craniofacial abnormalities. Given their uncommonness, a comprehensive genotype-phenotype correlation has not fully been defined. Case Presentation: We report the clinical and cytogenomic characterization of a 5-year-old boy with intellectual disability, psychomotor retardation, craniofacial dysmorphism, genital anomalies, and pure interstitial trisomy 11q arising from a nonrecurrent 11q13.1q22.3 intrachromosomal duplication in a high-mosaic state (>80%). The duplicated chromosome was characterized by cytogenetics, multicolor banding FISH, and SNP array. We demonstrated the wide mosaic distribution of the 11q duplication by interphase FISH in tissues from different embryonic germ layers. The duplication involves a copy number gain of 45.3 Mb containing 22 dosage-sensitive genes. We confirmed the overexpression of dosage-sensitive genes along the duplicated region using RT-qPCR. Discussion: Only 8 patients have been described. Our patient shares clinical features with previous reports but differs from them by the presence of genital anomalies. We provide a detailed clinical review and an accurate genotype-phenotype correlation and propose PC, NDUFV1, FGF3, FGF4, and DHCR7 as dosage-sensitive genes with a possible role in the clinical spectrum of our patient; however, expression changes of FGF3/4 were not detected since they must be regulated in a spatiotemporal way. This patient contributes to the accurate description of the pure interstitial trisomy 11q. Future reports could continue to delineate the description, considering the relationship between the chromosome segment and the genes involved.

Incidence of urological tumors in Down's syndrome: a systematic review and meta-analysis.

BACKGROUND: Some authors have estimated that the incidence of testicular germ cell tumors in individuals with trisomy 21 is more than fivefold higher than that in the general population. OBJECTIVE: This systematic review aimed to estimate the incidence of urological tumors in patients with Down's syndrome. STUDY DESIGN: We conducted a search strategy in MEDLINE (OVID), EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. We assessed the risk of bias and performed a meta-analysis. Also, the heterogeneity between trials was evaluated by the I2 test. We completed the subgroup analysis based on the type of urological tumor (testis, bladder, kidney, upper urological tract, penile, retroperitoneum). RESULTS: We found 350 studies by the search strategy. After carefully reviewing, full-text studies were included. 16,248 individuals with Down's syndrome were included, and 42 patients presented with urological tumors. There was a total incidence of 0.1%, 95%CI (0.06-0.19), I2 61%. The most common urological tumor reported was testicular. We found six studies describing 31 events and an overall incidence of 0.19%, 95%CI (0.11-0.33), I2: 51%. Other studies reported kidney, penile, upper urinary tract, bladder, and retroperitoneum tumors with a very low incidence, 0.02%, 0.06%, 0.03%, 0.11%and 0.07%, respectively. DISCUSSION: Regarding non-testicular urological tumors, we found incidences as low as 0.02% in kidney cancer or 0.03% in the upper-urothelial tract tumors. It is also lower than the general population. Compared to the age of onset of patients, it is also lower than the general population, perhaps related to a shorter life expectancy. As a limitation, we found a high heterogeneity and a lack of information regarding non-testicular tumors. CONCLUSION: There was a very low incidence of urological tumors in people with Down's syndrome. Testis tumor was the most frequently described in all cohorts and within a normal distribution range.

Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome.

Down syndrome (DS) is characterized by the trisomy of chromosome 21 and by cognitive deficits that have been related to neuronal morphological alterations in humans, as well as in animal models. The gene encoding for amyloid precursor protein (APP) is present in autosome 21, and its overexpression in DS has been linked to neuronal dysfunction, cognitive deficit, and Alzheimer's disease-like dementia. In particular, the neuronal ability to extend processes and branching is affected. Current evidence suggests that APP could also regulate neurite growth through its role in the actin cytoskeleton, in part by influencing p21-activated kinase (PAK) activity. The latter effect is carried out by an increased abundance of the caspase cleavage-released carboxy-terminal C31 fragment. In this work, using a neuronal cell line named CTb, which derived from the cerebral cortex of a trisomy 16 mouse, an animal model of human DS, we observed an overexpression of APP, elevated caspase activity, augmented cleavage of the C-terminal fragment of APP, and increased PAK1 phosphorylation. Morphometric analyses showed that inhibition of PAK1 activity with FRAX486 increased the average length of the neurites, the number of crossings per Sholl ring, the formation of new processes, and stimulated the loss of processes. Considering our results, we propose that PAK hyperphosphorylation impairs neurite outgrowth and remodeling in the cellular model of DS, and therefore we suggest that PAK1 may be a potential pharmacological target.

Cirugía plástica facial en niños con síndrome de Down / Facial Plastic Surgery in Children with Down Syndrome

Introducción: El síndrome de Down comprende diversos grados de retraso mental y un número de rasgos característicos en su facies. Debido a que estos pacientes presentan problemas en la vida social, laboral y educacional se han buscado soluciones que hagan de estos niños, individuos socialmente útiles. Este artículo muestra los resultados obtenidos en 22 pacientes con este síndrome que fueron tratados quirúrgicamente para corregir sus estigmas faciales. Objetivo: Demostrar los cambios funcionales y ventajas estéticas que se obtienen con la cirugía plástica facial en el paciente con síndrome de Down. Métodos: Se escogieron 22 pacientes con síndrome de Down de 3 a 14 años de edad en el período comprendido de 1986 a enero 2019. Se incluyeron los 15 primeros casos atendidos en el Hospital Pediátrico Docente William Soler en el Servicio de Cirugía Plástica y posteriormente en otros centros nacionales de salud. Los procederes quirúrgicos realizados para la corrección de los estigmas faciales fueron: glosectomía parcial, cantoplastia lateral, cantoplastia media y otoplastia. Resultados: Los cambios estéticos y funcionales fueron favorables, lo que mejoró la apariencia y eliminó los rasgos no atractivos. Se obtuvieron cambios positivos en el lenguaje y la respiración. La glosectomía y cantoplastia se realizó en el 100 por ciento de los casos. Conclusiones: Todos los pacientes operados atenuaron sus estigmas faciales, mientras que se reportaron beneficios respiratorios y mejoría en la esfera del lenguaje. El grado de satisfacción de los padres fue bueno(AU)

Introduction: Down syndrome comprises varying degrees of mental retardation and a number of characteristic facial features. Because these patients present problems in their social, occupational and educational life, solutions have been sought to make these children socially useful individuals. This work shows the results obtained in 22 patients with this syndrome who were surgically treated to correct their facial stigmata. Objective: To show the functional changes and aesthetic advantages obtained with facial plastic surgery in patients with Down syndrome. Methods: A number of 22 patients with Down syndrome aged 3 to 14 years were chosen, in the period from 1986 to January 2019. The first 15 cases attended in the plastic surgery service of Hospital Pediátrico Docente William Soler were included; later, others attended in other national health centers. The surgical procedures performed for the correction of facial stigmata were partial glossectomy, lateral canthoplasty, medial canthoplasty, and otoplasty. Results: Aesthetic and functional changes were favorable, improving appearance and eliminating unattractive features. Positive changes in speech and breathing were obtained. Glossectomy and otoplasty were performed in 100 percent of cases. Conclusions: All operated-on patients attenuated their facial stigmata, while respiratory benefits and speech improvement were reported. The degree of satisfaction of their parents was good(AU)

Chimerism 47,XY, + 8/46,XX: Follow-up for 11 Years.

Approximately 30 sex chromosome discordant chimera cases have been reported to date. In particular, there are few reported cases of chimerism involving coexisting normal and abnormal lineages that each carries a distinct sex chromosome complement. To our knowledge, this is the first case of sexual chimerism with a simultaneous chromosomal aneuploidy involving chromosome 8. This report represents the data from 11 years of follow-up.