Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia

Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P 1�4 2.15 � 10 � 120) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia

Gillespie syndrome in a South Asian child:a case report with confirmation of a heterozygous mutation of the ITPR1 gene and review of the clinical and molecular features

Abstract Background Gillespie syndrome is a rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia, non-progressive cerebellar ataxia and intellectual disability. Homozygous and heterozygous pathogenic variants of the ITPR1 gene encoding an inositol 1, 4, 5- triphosphate- responsive calcium channel have been identified in 13 patients recently. There have been 22 cases reported in the literature by 2016, mostly from the western hemisphere with none reported from Sri Lanka. Case presentation A 10-year-old girl born to healthy non-consanguineous parents with delayed development is described. She started walking unaided by 9 years with a significantly unsteady gait and her speech was similarly delayed. Physical examination revealed multiple cerebellar signs. Slit lamp examination of eyes revealed bilateral partial aniridia. Magnetic resonance imaging of brain at the age of 10 years revealed cerebellar (mainly vermian) hypoplasia. Genetic testing confirmed the clinical suspicion and demonstrated a heterozygous pathogenic variant c.7786_7788delAAG p.(Lys2596del) in the ITPR1 gene. Conclusion The report of this child with molecular confirmation of Gillespie syndrome highlights the need for careful evaluation of ophthalmological and neurological features in patients that enables correct clinical diagnosis. The availability of genetic testing enables more accurate counseling of the parents and patients regarding recurrence risks to other family members

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites

Congenital temporomandibular joint ankylosis: Clinical characterization and natural history of four unrelated affected individuals

The objective of this study was to describe four unrelated patients affected by congenital temporomandibular joint ankylosis. Clinical delineation, natural history, and possible etiologies are discussed. Clinical aspects that are important for follow-up are outlined.42669469

Gillespie syndrome: Additional findings and parental consanguinity

Aniridia is a rare condition whose presence should alert clinicians to the possibility of other abnormalities. One of the differential diagnoses that should be considered is Gillespie syndrome, in which aniridia is associated with cerebellar ataxia and mental retardation. There are only 21 reported cases of Gillespie syndrome. The goal of this paper is to describe the clinical manifestations of a girl born to a consanguineous couple who presented with typical findings of the Gillespie syndrome, in addition to previously undescribed alterations of her distal extremities.282899

Qualidade da notificação de anomalias congênitas pelo Sistema de Informações sobre Nascidos Vivos (SINASC): estudo comparativo nos anos 2004 e 2007 Quality of birth defect reporting in the Brazilian Information System on Live Births (SINASC): a comparative study of 2004 and 2007

Este estudo comparou a validade dos diagnósticos de anomalias congênitas do Sistema de Informações sobre Nascidos Vivos (SINASC), em oito hospitais distribuídos em sete municípios do Brasil, totalizando 27.945 nascidos vivos em 2004 e 25.905 em 2007. Além disso, descreveu ações específicas realizadas para o aprimoramento da qualidade dos dados desse campo. Para a análise da validade, foi utilizado o Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC) como padrão-ouro. Em 2004, pelo menos 40% dos casos de anomalias congênitas eram subnotificados, situação que não foi modificada em 2007. Observou-se aumento significativo na sensibilidade somente em um hospital, de 56,9% para 96,8%. Em dois hospitais, houve diminuição significativa na sensibilidade, de 62,7% para 41,7% e de 66,5% para 32,2%. Os valores preditivos positivo e negativo e especificidade permaneceram acima de 80%. Apenas duas secretarias municipais de saúde e quatro hospitais fizeram algum tipo de ação específica para a melhoria do campo 34. Os resultados apontam para a necessidade de se investir na qualidade da informação sobre anomalias congênitas no SINASC.<br>This study compared the validity of birth defect cases reported in the Brazilian Information System on Live Births in 2004 and 2007 in seven municipalities, out of a total of 27,945 live births in 2004 and 25,905 in 2007. The study also describes quality improvement measures in this area. The Latin American Collaborative Study on Congenital Malformations was used as the gold standard for analyzing the validity of birth defect diagnoses. In 2004, at least 40% of birth defects went unreported, and this situation persisted in 2007. Only one hospital showed a significant increase in reporting sensitivity, from 56.9% to 96.8%. Sensitivity decreased significantly in two hospitals (from 62.7% to 41.75% and from 66.5% to 32.2%, respectively). The positive and negative predictive values and specificity remained above 80%. Only two municipal health departments and four hospitals implemented measures to improve reporting of birth defects. The results indicate the need for investments in the quality of birth defect information on birth certificates

3D Acquisition of the Ear Anatomy: A Low-Cost Set up Suitable for the Clinical Practice

The most common clinical treatment for ear deformities or non-congenital abnormalities is the reconstruction of the missing geometry using autologous costal cartilage. The surgical procedure consists in cutting, sculpting and suturing harvested costal cartilage from the patient to recreate an ear shape which is symmetric to the contralateral ear. During chirurgical operation, surgeons needs an accurate 3D template as reference to reproduce the ear. For this purpose, reverse engineering and additive manufacturing techniques can be employed. Specifically, this works aims to develop a reliable, low-cost and user-friendly system, to acquire the healthy ear geometry in clinical environment avoiding head patient\u2019s exposition to radiation (MRI, CT scan). An ideal acquisition setup and device have been selected to achieve accurate results. To this end, a casted model of an ear was created as reference, and the best setup was evaluated by comparing the obtained 3D reconstructions with it. Once the setup has been determined, the anatomies of five volunteers were acquired, to test the methodology on human subjects