Hipocondroplasia en pediatría: reporte de un caso / Hypocondroplasya in pediatrics: case study / Hipocondroplasia em pediatia: relato de caso

La hipocondroplasia es una displasia esquelética caracterizada por baja estatura, constitución robusta, brazos y piernas desproporcionadamente cortos, manos y pies anchos y cortos, leve laxitud articular y macrocefalia. Los niños generalmente se presentan como pequeños, con velocidad de crecimiento disminuida, que conduce a una baja estatura y desproporción de las extremidades. La hipocondroplasia en la mayoría de los casos se hereda con carácter autosómico dominante, aunque se detectan numerosos casos esporádicos. El diagnóstico requiere una exhaustiva anamnesis y adecuada exploración física. Es importante valorar algunos indicadores de crecimiento como: peso para la edad, longitud/talla para la edad, relación entre peso y longitud/talla, velocidad de crecimiento, talla diana genética, medidas de segmentos corporales, entre otros. Las radiografías esqueléticas permiten diagnosticar la mayoría de las displasias óseas. Los estudios moleculares suelen ser la prueba de confirmación y se solicitan ante una sospecha diagnóstica. Es importante incluir las displasias óseas en el diagnóstico diferencial de la talla baja y tenerlas en cuenta ante cualquier caso de talla baja disarmónica con alteraciones fenotípicas. La hipocondroplasia en la actualidad, no es una indicación aprobada para tratamiento con hormona del crecimiento. Se presenta un caso clínico de una niña de 14 meses, con talla baja severa, desproporcionada, que presentó dificultades para llegar al diagnóstico definitivo de hipocondroplasia.

Hypochondroplasia is a skeletal dysplasia characterized by short height, robust build, disproportionately short arms and legs, short and broad hands and feet, mild joint laxity, and macrocephaly. Children generally show slow growth rate, which leads to short stature and limb disproportion. Hypochondroplasia is mostly inherited with an autosomal dominant character, although many sporadic cases have been detected. Diagnosis requires a thorough history and adequate physical examination. It is important to assess some growth indicators such as: weight for age, length/height for age, relationship between weight and length/height, growth speed, genetic target height, measurements of body segments, among others. Skeletal XRs can diagnose most bone dysplasias. Molecular studies are usually the confirmatory test and are requested when a diagnosis is suspected. It is important to include bone dysplasias in the differential diagnosis of short stature and to take them into account for any disharmonious short stature with phenotypic alterations. Hypochondroplasia is currently not an approved indication for growth hormone therapy. We present a clinical case of a 14-month-old girl, with a severe, disproportionate short stature, who presented difficulties in her definitive hypochondroplasia diagnosis.

A hipocondroplasia é uma displasia esquelética caracterizada por baixa estatura, constituição robusta, braços e pernas desproporcionalmente curtos, mãos e pés largos e curtos, frouxidão articular leve e macrocefalia. As crianças geralmente são pequenas, com diminuição da velocidade de crescimento, o que leva à baixa estatura e desproporção dos membros. A hipocondroplasia na maioria dos casos é herdada com caráter autossômico dominante, embora sejam detectados numerosos casos esporádicos. O diagnóstico requer uma história completa e um exame físico adequado. É importante avaliar alguns indicadores de crescimento como: peso para idade, comprimento/altura para idade, relação entre peso e comprimento/altura, taxa de crescimento, estatura alvo genético, medidas de segmentos corporais, entre outros. As radiografias esqueléticas permitem o diagnóstico da maioria das displasias ósseas. Os estudos moleculares são geralmente o teste de confirmação e são solicitados quando há suspeita de diagnóstico. É importante incluir as displasias ósseas no diagnóstico diferencial da baixa estatura e considerá-las em qualquer caso de baixa estatura desarmônica com alterações fenotípicas. A hipocondroplasia não é atualmente uma indicação aprovada para o tratamento com hormônio de crescimento. Apresenta-se o caso clínico de uma menina de 14 meses, com baixa estatura grave e desproporcional, que apresentou dificuldades em chegar ao diagnóstico definitivo de hipocondroplasia.

High frequency of genetic/epigenetic disorders in short stature children born with very low birth weight.

Most infants born with very low birth weight (VLBW, birth weight < 1500 g) show spontaneous catch-up growth in postnatal life. The reasons for the absence of catch-up growth are not entirely understood. We performed a comprehensive investigation of 52 children born with VLBW. Ten children had a history of an external cause that explained the VLBW and five refused genetic evaluation. Twenty-three cases were initially evaluated by a candidate gene approach. Patients with a negative result in the candidate gene approach (n = 14) or without clinical suspicion (n = 14) were assessed by chromosome microarray analysis (CMA) and/or whole-exome sequencing (WES). A genetic condition was identified in 19 of 37 (51.4%) patients without an external cause, nine by candidate gene approach, and 10 by a genomic approach (CMA/WES). Silver-Russell syndrome was the most frequent diagnosis (n = 5) and the remaining patients were diagnosed with other rare monogenic conditions. Almost all patients with a positive genetic diagnosis exhibited syndromic features (94.4%). However, microcephaly, neurodevelopmental disorders, major malformation, or facial dysmorphism were also frequently observed in children with an external cause. In conclusion, a significant proportion of children born with VLBW with persistent short stature have a genetic/epigenetic condition.

Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

Prevalence and determinants of stunting among preschool and school-going children in the flood-affected areas of Pakistan / Prevalência e determinantes da baixa estatura entre crianças em idade pré escolar e em idade escolar nas áreas afetadas pelas enchentes do Paquistão

Stunting is a significant public health problem in low- and middle-income countries. This study assessed the prevalence of stunting and associated risk factors of stunting among preschool and school-going children in flood-affected areas of Pakistan. A cross-sectional study was conducted by visiting 656 households through multi-stage sampling. Respondent's anthropometric measurements, socio-demographic information and sanitation facilities were explored. A logistic regression model was used to determine determinants of stunting, controlling for all possible confounders. The overall prevalence of stunting in children was 40.5%, among children 36.1% boys and 46.3% of girls were stunted. The prevalence of stunting in under-five children was 50.7%. Female children (OR=1.35, 95% CI:0.94-2.0), children aged 13-24 months (OR=6.5, 95% CI: 3.0-13.9), mothers aged 15-24 years (OR=4.4, 95% CI: 2.6-7.2), joint family (OR=2.1, 95% CI: 1.4-3.0) did not have access to improved drinking water (OR=3.3, 95% CI: 1.9-5.9), and the toilet facility (OR=2.8, 95% CI, 1.9-4.3), while the children from district Nowshera (OR=1.7, 95% CI: 0.9-3.2) were significantly (P<0.05) associated in univariate analysis. The regression model revealed that child age, maternal age, family type, quality of water, and toilet facility, were the significant (P<0.05) factors contributing to child stunting in the flood-hit areas. Identification of key factors might be helpful for policymakers in designing comprehensive community-based programs for the reduction of stunting in flood-affected areas. In disasters such as flood, the detrimental consequences of the stunting problem could be even more on children. Evidence-based education and care must be provided to the families in the flood-affected regions to reduce the stunting problem. The determinants of stunting should [...].(AU)

A baixa estatura é um problema significativo de saúde pública em países de baixa e média renda. Este estudo avaliou a prevalência de nanismo e os fatores de risco associados de nanismo entre crianças em idade pré-escolar e em idade escolar em áreas afetadas por inundações do Paquistão. Foi realizado um estudo transversal visitando 656 domicílios por meio de amostragem em múltiplos estágios. As medidas antropométricas do entrevistado, informações sociodemográficas e instalações de saneamento foram exploradas. Um modelo de regressão logística foi usado para determinar os determinantes do nanismo, controlando todos os possíveis fatores de confusão. A prevalência geral de baixa estatura em crianças foi de 40,5%, entre as crianças 36,1% dos meninos e 46,3% das meninas com baixa estatura. A prevalência de baixa estatura em crianças menores de 5 anos foi de 50,7%. Crianças do sexo feminino (OR = 1,35, IC de 95%: 0,94-2,0), crianças de 13-24 meses (OR = 6,5, IC de 95%: 3,0-13,9), mães de 15-24 anos (OR = 4,4, IC de 95%: 2,6-7,2), família conjunta (OR = 2,1, IC 95%: 1,4-3,0) não tiveram acesso a água potável de qualidade (OR = 3,3, IC 95%: 1,9-5,9) e a banheiro (OR = 2,8, IC de 95%, 1,9-4,3), enquanto as crianças do distrito de Nowshera (OR = 1,7, IC de 95%: 0,9-3,2) foram significativamente (P < 0,05) associadas na análise univariada. O modelo de regressão revelou que a idade da criança, idade materna, tipo de família, qualidade da água e banheiro foram os fatores significativos (P < 0,05) que contribuíram para a baixa estatura infantil nas áreas afetadas pelas enchentes. A identificação de fatores-chave pode ser útil para os formuladores de políticas no planejamento de programas comunitários abrangentes para a redução da baixa estatura em áreas afetadas pelas enchentes. Em desastres como enchentes, as consequências prejudiciais do problema de baixa estatura podem [...].(AU)

Prevalence and determinants of stunting among preschool and school-going children in the flood-affected areas of Pakistan / Prevalência e determinantes da baixa estatura entre crianças em idade pré escolar e em idade escolar nas áreas afetadas pelas enchentes do Paquistão

Stunting is a significant public health problem in low- and middle-income countries. This study assessed the prevalence of stunting and associated risk factors of stunting among preschool and school-going children in flood-affected areas of Pakistan. A cross-sectional study was conducted by visiting 656 households through multi-stage sampling. Respondent's anthropometric measurements, socio-demographic information and sanitation facilities were explored. A logistic regression model was used to determine determinants of stunting, controlling for all possible confounders. The overall prevalence of stunting in children was 40.5%, among children 36.1% boys and 46.3% of girls were stunted. The prevalence of stunting in under-five children was 50.7%. Female children (OR=1.35, 95% CI:0.94-2.0), children aged 13-24 months (OR=6.5, 95% CI: 3.0-13.9), mothers aged 15-24 years (OR=4.4, 95% CI: 2.6-7.2), joint family (OR=2.1, 95% CI: 1.4-3.0) did not have access to improved drinking water (OR=3.3, 95% CI: 1.9-5.9), and the toilet facility (OR=2.8, 95% CI, 1.9-4.3), while the children from district Nowshera (OR=1.7, 95% CI: 0.9-3.2) were significantly (P<0.05) associated in univariate analysis. The regression model revealed that child age, maternal age, family type, quality of water, and toilet facility, were the significant (P<0.05) factors contributing to child stunting in the flood-hit areas. Identification of key factors might be helpful for policymakers in designing comprehensive community-based programs for the reduction of stunting in flood-affected areas. In disasters such as flood, the detrimental consequences of the stunting problem could be even more on children. Evidence-based education and care must be provided to the families in the flood-affected regions to reduce the stunting problem. The determinants of stunting should [...].

A baixa estatura é um problema significativo de saúde pública em países de baixa e média renda. Este estudo avaliou a prevalência de nanismo e os fatores de risco associados de nanismo entre crianças em idade pré-escolar e em idade escolar em áreas afetadas por inundações do Paquistão. Foi realizado um estudo transversal visitando 656 domicílios por meio de amostragem em múltiplos estágios. As medidas antropométricas do entrevistado, informações sociodemográficas e instalações de saneamento foram exploradas. Um modelo de regressão logística foi usado para determinar os determinantes do nanismo, controlando todos os possíveis fatores de confusão. A prevalência geral de baixa estatura em crianças foi de 40,5%, entre as crianças 36,1% dos meninos e 46,3% das meninas com baixa estatura. A prevalência de baixa estatura em crianças menores de 5 anos foi de 50,7%. Crianças do sexo feminino (OR = 1,35, IC de 95%: 0,94-2,0), crianças de 13-24 meses (OR = 6,5, IC de 95%: 3,0-13,9), mães de 15-24 anos (OR = 4,4, IC de 95%: 2,6-7,2), família conjunta (OR = 2,1, IC 95%: 1,4-3,0) não tiveram acesso a água potável de qualidade (OR = 3,3, IC 95%: 1,9-5,9) e a banheiro (OR = 2,8, IC de 95%, 1,9-4,3), enquanto as crianças do distrito de Nowshera (OR = 1,7, IC de 95%: 0,9-3,2) foram significativamente (P < 0,05) associadas na análise univariada. O modelo de regressão revelou que a idade da criança, idade materna, tipo de família, qualidade da água e banheiro foram os fatores significativos (P < 0,05) que contribuíram para a baixa estatura infantil nas áreas afetadas pelas enchentes. A identificação de fatores-chave pode ser útil para os formuladores de políticas no planejamento de programas comunitários abrangentes para a redução da baixa estatura em áreas afetadas pelas enchentes. Em desastres como enchentes, as consequências prejudiciais do problema de baixa estatura podem [...].

High-Resolution Melting Analysis for Rapid Detection of Mutations in Patients with FGFR3-Related Skeletal Dysplasias.

Background: Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are related to skeletal dysplasias (SDs): acondroplasia (ACH), hypochodroplasia (HCH) and type I (TDI) and II (TDII) tanatophoric dysplasias. This study was designed to standardize and implement a high-resolution melting (HRM) technique to identify mutations in patients with these phenotypes. Methods: Initially, FGFR3 gene segments from 84 patients were PCR amplified and subjected to Sanger sequencing. Samples from 29 patients positive for mutations were analyzed by HRM. Results: Twelve of the patients FGFR3 mutations had ACH (six g.16081 G > A, three g.16081 G > C and three g.16081 G > A + g.16002 C > T); thirteen of patients with HCH had FGFR3 mutations (eight g.17333 C > A, five g.17333 C > G and five were negative); and four patients with DTI had FGFR3 mutations (three g.13526 C > T and one g.16051G > T and two patients with DTII (presented mutation g.17852 A > G). When analyzing the four SDs altogether, an overlap of the dissociation curves was observed, making genotyping difficult. When analyzed separately, however, the HRM analysis method proved to be efficient for discriminating among the mutations for each SD type, except for those patients carrying additional polymorphism concomitant to the recurrent mutation. Conclusion: We conclude that for recurrent mutations in the FGFR3 gene, that the HRM technique can be used as a faster, reliable and less expensive genotyping routine for the diagnosis of these pathologies than Sanger sequencing.

SOFT syndrome in a patient from Chile.

SOFT syndrome (MIM614813) is an extremely rare primordial dwarfism caused by biallelic mutations in the POC1A gene. It is characterized by prenatal short stature, onychodysplasia, facial dysmorphism, hypotrichosis, and variable skeletal abnormalities including hypoplastic pelvis and sacrum, small hands, and cone-shaped epiphyses, as well as delayed bone age. To the best of our knowledge, only eight POC1A mutations have been reported in humans to date. We report a 7-year-old Chilean girl with SOFT syndrome arising from a novel POC1A mutation c. 649C>T, p.Arg217Trp. Although her clinical features were largely compatible with SOFT syndrome, hand X-ray examinations at 3.5 and 6 years unexpectedly showed normal bone age. Automated bone age determination was performed using image analysis software, BoneXpert. This case highlights the importance of the accumulation of patients with POC1A mutations to further elucidate the detailed clinical features of SOFT syndrome.

Short stature as a presenting symptom of attenuated Mucopolysaccharidosis type I: case report and clinical insights.

BACKGROUND: Mucopolysaccharidosis type I (MPS I) results in significant disease burden and early treatment is important for optimal outcomes. Recognition of short stature and growth failure as symptoms of MPS I among pediatric endocrinologists may lead to earlier diagnosis and treatment. CASE PRESENTATION: A male patient first began experiencing hip pain at 5 years of age and was referred to an endocrinologist for short stature at age 7. Clinical history included recurrent respiratory infections, sleep apnea, moderate joint contractures, mild facial dysmorphic features, scoliosis, and umbilical hernia. Height was more than - 2 SD below the median at all time points. Growth velocity was below the 3rd percentile. Treatment for short stature included leuprolide acetate and recombinant human growth hormone. The patient was diagnosed with MPS I and began enzyme replacement therapy with laronidase at age 18. CONCLUSIONS: The case study patient had many symptoms of MPS I yet remained undiagnosed for 11 years after presenting with short stature. The appropriate path to MPS I diagnosis when patients present with short stature and/or growth failure plus one or more of the common signs of attenuated disease is described. Improved awareness regarding association of short stature and growth failure with attenuated MPS I is needed since early identification and treatment significantly decreases disease burden.

Dentoalveolar Abscesses Not Associated with Caries or Trauma: A Diagnostic Hallmark of Hypophosphatemic Rickets Initially Misdiagnosed as Hypochondroplasia.

Hypophosphatemic rickets is a rare genetic disorder involving the regulation of fibroblast growth factor 23 (FGF23), a phosphaturic agent, clinically showing bowing of the legs, short stature and dentoalveolar abscesses. A 7-year-old boy, with previous hypochondroplasia diagnosis, was referred to our pediatric dentistry clinic presenting short stature, bone deformities and sinus tracts at deciduous teeth apex levels not related with trauma, restorations or dental caries. After deciduous teeth extraction, due to root resorption and mobility, light microscopy exhibited typical hypophosphatemic dentin, and micro-computed tomography revealed tubular clefts and porosities throughout the teeth. Laboratory tests confirmed the HR diagnosis, after which the treatment was initiated.

Unique association of hypochondroplasia with craniosynostosis and cleft palate in a Mexican family.

Hypochondroplasia (HCH) is a skeletal dysplasia caused by an abnormal function of the fibroblast growth factor receptor 3. Although believed to be relatively common, its prevalence and phenotype are not well established owing to its clinical, radiological, and genetic heterogeneity. Here we report on a molecularly proven HCH family with an affected father and two children. The siblings (male and female) with HCH also had craniosynostosis and cleft palate, respectively. The present report supports the conclusion that the full clinical spectrum of HCH is not completely delineated. It also suggests that secondary, as yet unknown, modifying factors can influence the final phenotype.

Detection of enteric viruses in pancreas and spleen of broilers with runting-stunting syndrome (RSS) / Detecção de vírus entéricos em pâncreas e baço de frangos com a síndrome de nanismo e raquitismo (RSS)

Enteric disease is a multifactorial problem in chickens, which causes gastrointestinal alterations, elevated feed conversions and impairment. In the last years, several enteric viruses were implicated in enteric disease; case reports have shown their presence alone or in concomitant infections during outbreaks and have suggested that they might be determining factors in the aetiology of enteric disease. This study shows high detection rates of enteric viruses in the pancreas and spleen in samples from an outbreak of enteritis and malabsorption in 16 chicken flocks (n=80 broilers). Avian nephritis virus (ANV) was the most ubiquitous virus, present in 75% of the flocks followed by avian rotavirus group A (ART-A) with 68.75%, and by chicken astrovirus (CAstV) and chicken parvovirus (ChPV) in 43.75% of samples. Viruses were present in the pancreas of positive flocks at extremely high rates: 100% for ART-A, 91.7% for ANV, 100% for CAstV and 57.14% for ChPV. By contrast, only 16.7% and 57.14% of intestine samples were positive for ANV and CAstV, respectively. Avian reovirus (AReo) and avian adenovirus group 1 (FAdV-1) were not detected. These results suggest that high viral detection rates in pancreas samples may be a result of viremia during enteric disease, with subsequent damage of the exocrine pancreas, leading to runting-stunting syndrome (RSS).(AU)

A doença entérica é um problema multifatorial em galinhas que causa alterações gastrointestinais, conversão alimentar elevada e deficiência de crescimento. Nos últimos anos, os vírus entéricos foram associados à doença entérica; casos reportados mostraram a infecção de um único vírus e também infecções concomitantes durante os surtos sugerindo a presença de múltiplos fatores etiológicos nas doenças entéricas. Este estudo mostra uma alta taxa de detecção dos vírus entéricos em amostras de pâncreas e baço de um surto de enterite e má-absorção em 16 lotes de frangos (n=80 frangos). O vírus de nefrite aviária (ANV) foi o vírus mais detectado, estando presente em 75% dos lotes seguido pelo rotavírus aviário grupo A (ART-A) em 68,75% dos casos, e pelo astrovirus (CAstV) e parvovírus aviários (ChPV), ambos em 43,75% das amostras. Os vírus estavam presentes no pâncreas dos lotes positivos em percentuais elevados: 100% para ART-A e CAstV; 91,7% para ANV, e em 57,14% para ChPV. Em contraste, somente 16,7% e 57,14%, em amostras de intestino, foram positivos para ANV e CAstV, respectivamente. Reovírus aviário (AReo) e o adenovírus do grupo 1 (FAdV-1) não foram detectados. Estes resultados sugerem que os elevados percentuais de vírus detectados em amostras de pâncreas podem estar associados à viremia durante a doença entérica, com subsequente lesão no pâncreas exócrino das aves levando ao desenvolvimento da síndrome de nanismo e raquitismo.(AU)

Detection of enteric viruses in pancreas and spleen of broilers with runting-stunting syndrome (RSS) / Detecção de vírus entéricos em pâncreas e baço de frangos com a síndrome de nanismo e raquitismo (RSS)

Enteric disease is a multifactorial problem in chickens, which causes gastrointestinal alterations, elevated feed conversions and impairment. In the last years, several enteric viruses were implicated in enteric disease; case reports have shown their presence alone or in concomitant infections during outbreaks and have suggested that they might be determining factors in the aetiology of enteric disease. This study shows high detection rates of enteric viruses in the pancreas and spleen in samples from an outbreak of enteritis and malabsorption in 16 chicken flocks (n=80 broilers). Avian nephritis virus (ANV) was the most ubiquitous virus, present in 75% of the flocks followed by avian rotavirus group A (ART-A) with 68.75%, and by chicken astrovirus (CAstV) and chicken parvovirus (ChPV) in 43.75% of samples. Viruses were present in the pancreas of positive flocks at extremely high rates: 100% for ART-A, 91.7% for ANV, 100% for CAstV and 57.14% for ChPV. By contrast, only 16.7% and 57.14% of intestine samples were positive for ANV and CAstV, respectively. Avian reovirus (AReo) and avian adenovirus group 1 (FAdV-1) were not detected. These results suggest that high viral detection rates in pancreas samples may be a result of viremia during enteric disease, with subsequent damage of the exocrine pancreas, leading to runting-stunting syndrome (RSS).(AU)

A doença entérica é um problema multifatorial em galinhas que causa alterações gastrointestinais, conversão alimentar elevada e deficiência de crescimento. Nos últimos anos, os vírus entéricos foram associados à doença entérica; casos reportados mostraram a infecção de um único vírus e também infecções concomitantes durante os surtos sugerindo a presença de múltiplos fatores etiológicos nas doenças entéricas. Este estudo mostra uma alta taxa de detecção dos vírus entéricos em amostras de pâncreas e baço de um surto de enterite e má-absorção em 16 lotes de frangos (n=80 frangos). O vírus de nefrite aviária (ANV) foi o vírus mais detectado, estando presente em 75% dos lotes seguido pelo rotavírus aviário grupo A (ART-A) em 68,75% dos casos, e pelo astrovirus (CAstV) e parvovírus aviários (ChPV), ambos em 43,75% das amostras. Os vírus estavam presentes no pâncreas dos lotes positivos em percentuais elevados: 100% para ART-A e CAstV; 91,7% para ANV, e em 57,14% para ChPV. Em contraste, somente 16,7% e 57,14%, em amostras de intestino, foram positivos para ANV e CAstV, respectivamente. Reovírus aviário (AReo) e o adenovírus do grupo 1 (FAdV-1) não foram detectados. Estes resultados sugerem que os elevados percentuais de vírus detectados em amostras de pâncreas podem estar associados à viremia durante a doença entérica, com subsequente lesão no pâncreas exócrino das aves levando ao desenvolvimento da síndrome de nanismo e raquitismo.(AU)

Homozygous N540K hypochondroplasia--first report: radiological and clinical features.

We describe a 16-month-old male with N540K homozygous mutation in the FGFR3 gene who showed a more severe phenotype than hypochondroplasia (HCH). To our knowledge, a homozygous state for this mutation causing HCH has not been reported before. The clinical and radiological characteristics of our patient represent an intermediate condition between achondroplasia and achondroplasia/hypochondroplasia compound heterozygosity. This case represents a new expression of FGFR3 spectrum and it is of considerable importance for the genetic counseling in cases where both parents are affected with HCH.

Doença periodontal em adultos com Deficiência Isolada do Hormônio do Crescimento: aspectos clínicos, microbiológicos e imunológicos / Periodontal disease in adults with isolated growth hormone deficiency: clinical, microbiological and immunological aspects

Indivíduos com Deficiência Isolada do Hormônio do Crescimento (IGHD), homozigotos para a mutação c.57+1G>A no gene do receptor do hormônio liberador do hormônio de crescimento (GHRH), apresentam maior chance de apresentarem perda de inserção periodontal devido a possível efeito direto da IGHD sobre os tecidos periodontais e/ou a repercussões locais ou sistêmicas da IGHD sobre a resposta imune. Este estudo teve como objetivos avaliar as repercussões locais e sistêmicas da IGHD sobre a resposta imune e comparar os níveis dos patógenos periodontais. Material e Métodos: Foi composto por uma amostra de 19 indivíduos com IGHD e 19 indivíduos no grupo controle, pareados por idade, gênero, condição sócio-econômica, tabagismo e diabetes. Todos foram submetidos a exame periodontal completo, em 6 sítios por dente, e entrevistados por meio de um questionário estruturado. Foi realizada coleta de biofilme subgengival (em sítios rasos e profundos, pareados pela PCS) para verificar os níveis dos microorganismos. Além disso, foram realizadas coletas do fluido gengival (dos mesmos sítios) e do sangue, de ambos os grupos, com a finalidade de analisar o perfil das citocinas inflamatórias. Resultados: Indivíduos com IGHD apresentaram maior quantidade de MMP-8 e CRP (p=0,026 e 0,002) no fluido gengival coletado dos sítios profundos, maior quantidade de IL-17 (p=0,02) no soro e mesmos níveis dos patógenos periodontais, em comparação com os controles (p>0,05). Conclusões: Mesmo com um perfil microbiológico semelhante, indivíduos com a IGHD apresentam alterações imunológicas moderadas (aumento de Interleucina 17 no soro e de metaloproteinase-8 e Proteína C-Reativa no fluido gengival coletado de sítios profundos), comparados aos controles.

Isolated Growth Hormone Deficiency (IGHD) subjects, homozygous to a mutation c.57+1G>A in the growth hormone releasing hormone receptor (GHRHR) gene, have a greater chance of having periodontal attachment loss (PAL) due to a possible direct effect of IGHD on the periodontal tissues and/or locals and systemic effects of IGHD on immune response. This aims of this study was evaluate local and systemic effects of IGHD on immune response and compare periodontal pathogens levels. Material and Methods: The sample was composed of 19 IGHD individuals and 19 controls, matched by age, gender, socio-economic condition, smoking and diabetes. Participants were submitted to a clinical full-mouth periodontal examination of six sites per tooth and were interviewed using a structured questionnaire. Subgingival biofilm was collected (in shallow and deep sites matched by probing clinical depth) to check the periodontal pathogens levels. Futhermore, gingival crevicular fluid (same sites) and blood samples were also collected from both groups to analyze inflammatory cytokines profile. Results: IGHD subjects had significantly higher amounts of MMP-8 and CRP (p= 0.026 e 0.002) in the gingival crevicular fluid collected from deep sites, higher amounts of IL-17 (p=0.02) in serum, and same levels of periodontal pathogens, compairing to the control group (p>0.05). Conclusions: Despite the same microorganism profile, IGHD subjects had moderate immunological alterations (increased serum Interleukin 17 and metalloproteinase 8 and C - reactive protein in deep sites gingival fluid), comparing to controls.

A compound heterozygote SLC26A2 mutation resulting in robin sequence, mild limbs shortness, accelerated carpal ossification, and multiple epiphysial dysplasia in two Brazilian sisters. A new intermediate phenotype between diastrophic dysplasia and recessive multiple epiphyseal dysplasia.

Mutations in solute carrier family 26 (sulfate transporter), member 2 (SLC26A2) gene result in a spectrum of autosomal recessive chondrodysplasias that range from the mildest recessive form of multiple epiphysial dysplasia (rMED) through the most common diastrophic dysplasia (DTD) to lethal atelosteogenesis type II and achondrogenesis IB. The clinical variability has been ascribed to quantitative effect of mutations of the sulfate transporter activity. Here we describe two Brazilian sisters, born to healthy and non consanguineous parents, with Robin sequence, mild shortening of upper and lower limbs, brachymetacarpalia/tarsalia, additional and accelerated carpal ossification, marked genu valgum, and multiple epiphysial dysplasia. This phenotype was intermediate between DTD and rMED, and both girls have a compound heterozygous mutations for the SLC26A2, a Finnish founder mutation (c.-26 + 2T>C), and R279W. This combination of mutations has been observed in individuals with different phenotypes, including DTD, DTD variant, and rMED. The distinct phenotype of our cases reinforces the hypothesis that other factors may be influencing the phenotype as previously suggested.

A novel phenotype characterized by digital abnormalities, intellectual disability, and short stature in a Mexican family maps to Xp11.4-p11.21.

The family observed in this study included affected males and asymptomatic females. The patients shared specific digital abnormalities including postaxial polydactyly, cutaneous syndactyly, and brachydactyly. In addition, the patients exhibited mild-to-moderate intellectual disability and short stature coupled with microbrachycephaly, scoliosis, and cerebellar and renal hypoplasia. No chromosomal alterations or copy number variations were found in the index case. The genetic linkage analysis, which focused on the X chromosome, and the haplotype analysis detected a ~15.74 Mb candidate region located at Xp11.4-p11.21 with a LOD score of 4.8. Additionally, half of the mothers showed skewed X-inactivation, while the other mothers exhibited random inactivation patterns. The candidate region includes 28 protein-encoding genes that have not yet been implicated in human disorders. We speculate that the observed phenotype is compatible with a monogenic disorder in which the mutant gene plays a significant role during embryonic development. Based on the patients' clinical features, image studies, pedigree, chromosome location, and X-inactivation studies in the mothers, we propose that this family has a novel, specific syndrome with an X-linked recessive mode of inheritance.

Whole exome sequencing reveals a novel mutation in CUL7 in a patient with an undiagnosed growth disorder.

We present the case of a 19-year-old man with a growth disorder, which was undefined, despite extensive evaluation. Whole exome sequencing demonstrated a novel homozygous frameshift mutation in CUL7, one of the causative genes of 3-M syndrome. We discuss the utility of exome sequencing in diagnosing rare disorders.