Minimal Critical Region and Genes for a Typical Presentation of Langer-Giedion Syndrome.

Langer-Giedion syndrome (LGS) is caused by a contiguous deletion at 8q23q24, characterized by exostoses, facial, ectodermal, and skeletal anomalies, and, occasionally, intellectual disability. LGS patients have been diagnosed clinically or by routine cytogenetic techniques, hampering the definition of an accurate genotype-phenotype correlation for the syndrome. We report two unrelated patients with 8q23q24 deletions, characterized by cytogenomic techniques, with one of them, to our knowledge, carrying the smallest deletion reported in classic LGS cases. We assessed the pathogenicity of the deletion of genes within the 8q23q24 region and reviewed other molecularly confirmed cases from the literature. Our findings suggest a 3.2-Mb critical region for a typical presentation of the syndrome, emphasizing the contribution of the TRPS1, RAD21, and EXT1 genes' haploinsufficiency, and facial dysmorphisms as well as bone anomalies as the most frequent features among patients with LGS. We also suggest a possible role for the CSMD3 gene, whose deletion seems to contribute to central nervous system anomalies. Since studies performing such correlation for LGS patients are limited, our data contribute to improving the ge-notype-phenotype characterization for LGS patients.

Multicentric Carpotarsal Osteolysis Syndrome in a Mother and Daughter with a MAFB Missense Variant and Natural History of the Disease.

Multicentric carpotarsal osteolysis syndrome (MCTO; MIM #166300) is a rare skeletal disorder characterized by osteolysis affecting particularly the carpal, metacarpal, and tarsal bones, although other bones might be involved. MCTO is an autosomal dominant disease caused by heterozygous variants in the MAFB gene, frequently misdiagnosed as juvenile rheumatoid arthritis due to similar clinical manifestations. This study reports the first Brazilian family diagnosed with MCTO with progressive osteolysis of the carpal and tarsal bones, presenting a c.161C>T (p.Ser54Leu) heterozygous variant in the MAFB gene, describing the clinical, radiological, and molecular findings, compared with literature data, and discussing the different clinical and molecular diagnosis, as well as the natural history of the disease. Since MCTO is a disorder with progressive symptoms, an early diagnosis is important to avoid unnecessary investigations and treatments and to provide the proper follow-up.

Overlapping phenotype comprising Kenny-Caffey type 2 and Sanjad-Sakati syndromes: The first case report.

Kenny-Caffey syndrome (KCS) is a rare hereditary skeletal disorder involving hypoparathyroidism. The autosomal dominant form (KCS2), caused by heterozygous pathogenic variants in the FAM111A gene, is distinguished from the autosomal recessive form (KCS1) and Sanjad-Sakati syndrome (SSS), both caused by pathogenic variants in the tubulin folding cofactor E (TBCE) gene, by the absence of microcephaly and intellectual disability. We present a patient with KCS2 caused by a de novo pathogenic variant c.1706G>A (p.Arg569His) in FAM111A gene, presenting intellectual disability and microcephaly, which are considered to be typical signs of SSS. We suggest that KCS1, KCS2, and SSS may not represent mutually exclusive clinical entities, but possibly an overlapping spectrum.

Schmid metaphyseal chondrodysplasia: an example of radiology guidance to molecular diagnosis.

Schmid metaphyseal chondrodysplasia is a rare genetic cause of skeletal dysplasia. Patients usually present skeletal abnormalities but no major visceral malformations or intellectual disability. We report a case of a 2-year-old male patient with short stature, progressive genu varum, and waddling gait. Radiographic findings were essential to guide investigation and molecular confirmation, allowing proper treatment and genetic counseling.

Leigh syndrome in a patient with a novel C12orf65 pathogenic variant: case report and literature review.

Leigh syndrome is an early onset progressive disorder caused by defects in mitochondrial oxidative phosphorylation. Pathogenic variants in nuclear and mitochondrial genes are associated with the syndrome. Homozygous pathogenic variants in the C12orf65 gene impair the mitochondrial oxidative phosphorylation system. We describe a new case of Leigh syndrome caused by a novel pathogenic variant of the C12orf65 gene resulting in the lack of the Gly-Gly-Gln (GGQ) domain in the predicted protein, and review clinical and molecular data from previously reported patients. Our study supports that the phenotype caused by C12orf65 gene variants is heterogeneous and varies from spastic paraparesis to Leigh syndrome. Loss-of-function variants are more likely to cause the disease, and variants affecting the GGQ domain tend to be associated with more severe phenotypes, reinforcing a possible genotype-phenotype correlation.

Gomez-López-Hernández syndrome: A case report with clinical and molecular evaluation and literature review.

Gomez-López-Hernández syndrome (GLHS) is characterized by rhombencephalosynapsis (RES), alopecia, trigeminal anesthesia and a distinctive phenotype, including brachyturricephaly. It has been suggested that GLHS should be considered as part of the spectrum of RES-associated conditions that include alopecia, trigeminal anesthesia, and craniofacial anomalies, rather than a distinct entity. To the best of our knowledge, 57 patients with GLHS have been described. Despite its first description in 1979, the etiology of this syndrome remains unknown. Here, we describe, to our knowledge, the first case of a patient with GLHS who was molecularly evaluated and had been prenatally exposed to misoprostol. We also reviewed the clinical and morphological features of the patients described to date to better delineate the phenotype and focus on any evidence for adverse pregnancy outcomes or exposure, including teratogens.

Untreated Congenital Hypothyroidism Mimicking Hirschsprung Disease: A Puzzling Case in a One-Year-Old Child.

Congenital hypothyroidism is a clinical emergency due to its potential risk of mental retardation. Constipation might be present in hypothyroid children. However, Hirschsprung disease is rarely associated with congenital hypothyroidism. Herein, a case of congenital hypothyroidism in a one-year-old child mimicking Hirschsprung disease is described. Adequate treatment with levothyroxine sodium tablets controlled intestinal dysmotility that mimicked congenital intestinal aganglionosis due to the critical influence of thyroid hormones on bowel motility.

Inactivation of AMMECR1 is associated with growth, bone, and heart alterations.

We report five individuals with loss-of-function of the X-linked AMMECR1: a girl with a balanced X-autosome translocation and inactivation of the normal X-chromosome; two boys with maternally inherited and de novo nonsense variants; and two half-brothers with maternally inherited microdeletion variants. They present with short stature, cardiac and skeletal abnormalities, and hearing loss. Variants of unknown significance in AMMECR1 in four male patients from two families with partially overlapping phenotypes were previously reported. AMMECR1 is coexpressed with genes implicated in cell cycle regulation, five of which were previously associated with growth and bone alterations. Our knockdown of the zebrafish orthologous gene resulted in phenotypes reminiscent of patients' features. The increased transcript and encoded protein levels of AMMECR1L, an AMMECR1 paralog, in the t(X;9) patient's cells indicate a possible partial compensatory mechanism. AMMECR1 and AMMECR1L proteins dimerize and localize to the nucleus as suggested by their nucleic acid-binding RAGNYA folds. Our results suggest that AMMECR1 is potentially involved in cell cycle control and linked to a new syndrome with growth, bone, heart, and kidney alterations with or without elliptocytosis.

Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families.

Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed.

Radiografia simples de abdome no diagnóstico da impactação fecal em crianças com constipação intestinal: comparação entre três escores radiológicos / Abdominal radiograph in the assessment of fecal impaction in children with functional constipation: comparing three scoring systems

OBJETIVOS: Comparar três escores radiológicos na pesquisa de impactação fecal em crianças com constipação intestinal. Verificar, ainda, se estes escores radiológicos são úteis na avaliação da terapia de desimpactação fecal e se apresentam relação com o tempo de trânsito colônico total. MATERIAL E MÉTODOS: Os escores de Barr, Blethyn e Leech foram aferidos por três observadores, de forma independente, em 123 radiografias de abdome. A concordância interobservador no diagnóstico da impactação fecal foi calculada para os três escores. Em 30 radiografias, foi feita a análise dos escores antes e após a desimpactação fecal. O tempo de trânsito colônico total foi calculado em 59 radiografias com o emprego de marcadores radiopacos. RESULTADOS: A concordância entre os pares de observadores, avaliada pelo coeficiente de Kappa, foi boa para os escores de Barr (0,56, 0,59 e 0,69) e Leech (0,53, 0,58 e 0,61). O escore de Blethyn apresentou menores coeficientes de Kappa (0,26, 0,32 e 0,36). Na comparação dos métodos, Leech e Barr mostraram boa correlação. Após a desimpactação fecal, houve redução estatisticamente significante (p < 0,001) dos escores, mais expressiva com o escore de Barr. Não houve relação entre os escores radiológicos e o tempo de trânsito colônico. CONCLUSÕES: Não há relação entre impactação fecal avaliada pela radiografia de abdome e o tempo de trânsito colônico total. A radiografia simples pode ser um instrumento útil ao diagnóstico da impactação fecal. O escore de Barr pode ser considerado um bom método de análise, sobretudo para avaliação da resposta ao tratamento da impactação fecal.

OBJECTIVES: To compare three radiological scores in the study of fecal impaction in children with constipation. To investigate whether these radiological scores are useful in the assessment of fecal disimpaction therapy and if they present a relation with total colonic transit time. METHODS: The Barr, Blethyn and Leech scores were measured by three observers, independently, in 123 abdominal radiographs. Interobserver agreement in the diagnosis of fecal impaction was calculated for the three scores. In 30 radiographs, the analysis of the scores was performed before and after fecal disimpaction. Total colonic transit time was calculated in 59 radiographs with the use of radiopaque markers. RESULTS: The agreement between pairs of observers was assessed by the kappa coefficient and was good for the Barr (0.56, 0.59 and 0.69) and Leech scores (0.53, 0.58 and 0.61). The Blethyn score presented lower kappa coefficients (0.26, 0.32 and 0.36). In the comparison of methods, Leech and Barr showed a good correlation. After fecal disimpaction, there was a statistically significant reduction (p < 0.001) of scores, most significantly with the Barr score. There was no relation between radiographic scores and colonic transit time. CONCLUSIONS: There is no relation between fecal impaction assessed by radiography of the abdomen and total colonic transit time. Plain radiographs may be a useful tool for the diagnosis of fecal impaction. The Barr score can be considered a good method of analysis, especially to assess the response to treatment of fecal impaction.

Cytogenomic characterization of an unexpected 17.6 Mb 9p deletion associated to a 14.8 Mb 20p duplication in a dysmorphic patient with multiple congenital anomalies presenting a normal G-banding karyotype.

We describe a female patient with developmental delay, dysmorphic features and multiple congenital anomalies who presented a normal G-banded karyotype at the 550-band resolution. Array and multiplex-ligation probe amplification (MLPA) techniques identified an unexpected large unbalanced genomic aberration: a 17.6Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. The deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes. This study also shows the relevance of using molecular techniques to make an accurate diagnosis in patients with dysmorphic features and multiple anomalies suggestive of chromosome aberration, even if on G-banding their karyotype appears to be normal. Fluorescence in situ hybridization (FISH) was necessary to identify a masked balanced translocation in the patient's mother, indicating the importance of associating cytogenetic and molecular techniques in clinical genetics, given the implications for patient management and genetic counseling.

Impacto da úlcera de perna na vida da família: um estudo de caso / Impact of leg ulcer in family life: a case study

A úlcera de perna representa demanda crescente nos serviços de saúde. Por tratar-se de uma doença crônica, recorrente e de difícil manejo, a úlcera de perna é um problema que vem desafiando profissionais, pacientes e famílias. A necessidade de entender melhor a problemática existente no cuidado oferecido pelo enfermeiro ao paciente com úlcera e sua família, motivou a pergunta do estudo, a qual buscou responder como a família influencia e é influenciada pela úlcera de perna. O estudo teve como objetivo conhecer as percepções e crenças do paciente e de sua família em relação à úlcera de perna, bem como compreender como essas crenças influenciam o enfrentamento da família na experiência. O estudo de caso foi o método adotado, e as técnicas da história oral foram utilizadas para a coleta de dados. O estudo foi realizado com um casal idoso, o qual convive com a úlcera de perna da mulher, focando o impacto desse evento na história da família. As narrativas do casal permitiram a construção da memória coletiva organizada em três temas distintos os quais se inter-relacionam: Envelhecimento e doença, Jornada do tratamento, A ferida e o tempo. Os resultados permitiram compreender que a família influencia e é influenciada pela úlcera de perna e esta dinâmica determina um grande impacto na vida do casal que se encontra na fase tardia do ciclo de vida da família. O estudo identificou que as crenças do casal exercem grande influência sobre o impacto da doença em sua vida, além de determinar seu enfrentamento diante da situação. Este estudo, por considerar a família como categoria de análise, lança um novo olhar ao problema e acrescenta um conhecimento diferente no que se refere à relação entre a família e a ferida.Os resultados permitem uma reflexão acerca da importância do conhecimento profundo dos enfermeiros sobre as experiências dos pacientes e famílias que convivem com úlceras de perna. A valorização e o reconhecimento das forças da família no enfrentamento da doença e da mudança de comportamento do enfermeiro na prática clínica, a qual deve integrar um olhar além da ferida, considerando a interface entre a doença e o contexto familiar, são elementos capazes de estimular uma prática clínica centrada na família.

A leg ulcer is increasing demand on health services. Because it is chronic, recurrent and difficult to handle, leg ulcer is a problem that has defied professionals, patients and families. The need to better understand the problems existing in the care offered by nurses to patients with ulcer and their families led to the question of the study, which sought to answer how the family influences and is influenced by leg ulcer. The study aimed to understand the perceptions and beliefs of the patient and the family regarding leg ulcer as well as understand how these beliefs influence family coping experience. The case study method was adopted, and the techniques of oral history were used for data collection. The study was conducted with an elderly couple, who lives with woman\'s leg ulcer, focusing on the impact of this event in the family history. The narratives of the couple allowed the construction of collective memory organized into three distinct themes which are interrelated: Aging and illness, Journey of treatment, Wound and time. The results allowed to understand that family influences and is influenced by leg ulcers; family dynamics determines a great impact on the couples lives experiencing the late stage of the family life cycle. The study identified that the couples beliefs have great influence on the impact of the disease on their lives, and determine how they cope with the situation. This study, seeing the family as category of analysis, proposes a new perspective at the problem and adds new knowledge to the interaction between family and wound.The results allow a discussion about the importance of deep nursing knowledge about the experiences of patients and families living with leg ulcers. This new perspective requires a change in behavior of the nurse in clinical practice for a vision beyond the wound. The appreciation and recognition of the strengths of the family in coping with the illness and considering the interface between the disease and the family context are elements capable of stimulating a nursing family-centered practice.

A relação entre a equipe de enfermagem e o acompanhante de criança hospitalizada: facilidades e dificuldades / The relationship between the nursing team and the nursing aid that monitors the hospitalized child: easy aspects and difficulties

O estudo busca identificar as dificuldades e facilidades na relação da equipe de enfermagem com osacompanhantes das crianças hospitalizadas, bem como as estratégias utilizadas para o fortalecimento dessarelação. A pesquisa é descritivo-exploratória e quantitativa e foi realizada em um hospital público. Utilizou-se um formulário com questões sobre as facilidades, dificuldades e estratégias utilizadas para melhorar a relação profissional do enfermeiro com o acompanhante. As principais dificuldades foram: falta de comunicação, de informação sobre o tratamento, de material e de profissionais, além de tratamento desigual entre as crianças. As facilidades mais citadas foram: ser bom profissional tecnicamente, orientar sobre o tratamento, ter bomrelacionamento, manter diálogo, fazer medicações na hora certa e prestar uma assistência adequada à criança.As estratégias mais utilizadas foram: manter diálogo, transmitir confiança técnica, compreender e respeitar ooutro e respeitar as normas do hospital. É importante que o enfermeiro receba esse acompanhante para integrálona equipe, negociando suas funções na assistência à criança.

The purpose of this study is to identify the easy aspects and difficulties in the relationship between the nursingteam and the people who attend hospitalized children, and also identifying the strategies used to strengthen theirties. This was an exploratory descriptive quantitative approach survey, carried out at a public hospital. Aquestionnaire about the easy aspects, the difficulties and the strategies used to improve the professionalrelationship between the nurse and a person who attends hospitalized children, was applied. The main difficultiesfound were: the lack of communication, lack of information about the treatment, lack of supplies, lack of healthprofessionals, unequal treatment among children patients, and out of schedule medication. The easy aspects thatwere mentioned more often were: be a good technical professional, medication given on schedule, have a goodrelationship with patient, proper orientation about the treatment given to the family, interaction, attention, and carefor the child. The strategies most used were: dialogue, understand each other, respect, give technical confidence,and respect for hospital policies. It is important that the nursing aid receives follow up to be integrated in thenursing team, negotiating their duties related to the child care.

El estudio busca identificar las dificultades y facilidades en la relación del equipo de enfermería con losacompañantes de los niños hospitalizados, así como las estrategias utilizadas para el fortalecimiento de esarelación. La investigación es descriptiva-exploratoria y cuantitativa y fue realizada en un hospital público. Seutilizó un formulario con cuestiones sobre las facilidades, dificultades y estrategias utilizadas para mejorar larelación profesional del enfermero con el acompañante. Las principales dificultades fueron: falta decomunicación, de información sobre el tratamiento, de material y de profesionales, además de tratamientodesigual entre los niños. Las facilidades más citadas fueron: ser buen profesional técnicamente, orientar sobre eltratamiento, tener buena relación, mantener diálogo, hacer medicaciones en la hora cierta y prestar unaasistencia adecuada al niño. Las estrategias más utilizadas fueron: mantener diálogo, transmitir confianzatécnica, comprender y respetar al otro y respetar las normas del hospital. Es importante que el enfermero recibaese acompañante para integrarlo en el equipo, negociando sus funciones en la asistencia al niño.

Anemia aplástica e gravidez: relato de caso / Aplastic anemia and pregnancy: a case report

A anemia aplástica é distúrbio caracterizado por pancitopenia e medula óssea hipocelular, com substituição gordurosa dos elementos e sem nenhum sinal de transformação maligna ou doença mieloproliferativa. Acomete geralmente adultos jovens e idosos, sem preferência sexual. A maioria dos casos é adquirida, mas pode ocorrer hereditariamente, por distúrbio molecular (anemia de Fanconi). A associação com gravidez é rara, estando relacionada com alta morbidade e mortalidade materna e fetal. Os autores descrevem o caso de uma paciente com anemia aplástica, diagnosticada previamente, cuja gestação complicou com infecção do trato urinário, doença hipertensiva específica da gestação e restrição de crescimento fetal, com parto prematuro eletivo. Apesar das condições adversas na gravidez e parto, mäe e recém-nascido tiveram evolução clínica satisfatória

Características de recém-natos de mäes adolescentes: 157 casos / Characterized of newborns the adolescent mother: 157 case

Estudo prospectivo de 157 recém-natos e suas mäes adolescentes, atnedidas no serviço de prinatologia do CHDSGP (agosto 1987 a março 1988). Observou-se que a gestäo da adolescente, tanto para ela como para seu concepto, é de igual risco em qualquer faixa etaria dentro da adolescência. Nesta amostra a maior parte dos casos teve assistência pré-natal adequada, sem intercorrência perinatais, com RN de peso normal, a termo e adequados para a idade gestacional

Coexistência de gestaçäo tópica e ectópica: aspectos ultra-sonográficos / Coexistent intrauterina and ectopic pregnancy: ultrasonographic manifestations

Os autores descrevem dois casos de concomitância de gestaçäo tópica e ectópica, relatando os aspectos ecográficos e realizando uma breve revisäo de literatura. Enfatizam a necessidade de o ultra-sonografista realizar rotineiramente o estudo das regiöes anexiais em pacientes com gestaçäo tópica e morfologicamente normal