Neuroradiological findings in Alagille syndrome

Alagille syndrome (ALGS) is a multisystemic disease caused by mutations in genes of Notch pathway, which regulates embryonic cell differentiation and angiogenesis. Clinically, ALGS is characterized by cholestasis, cardiac defects, characteristic facial features, skeletal and ophthalmologic abnormalities. The aim of this review is to illustrate neuroradiological findings in ALGS, which are less well-known and prevalent, including cerebrovascular anomalies (such as aneurysms, dolichoectasia, Moyamoya syndrome and venous peculiarities), Chiari 1 malformation, craniosynostosis, intracranial hypertension, and vertebral anomalies (namely butterfly vertebra, hemivertebra, and craniocervical junction anomalies). Rarer cerebral midline malformations and temporal bone anomalies have also been described.

Recklinghausen neurofibromatosis variant

Neurofibromatosis is a hereditary disease characterized by the presence of many tumors located in the skin, along the peripheral nerves, in the central nervous system, skin pigmentation with bone anomalies, and damage to internal organs.

Differentially expressed genes in the femur cartilage transcriptome clarify the understanding of femoral head separation in chickens

Locomotor problems are among one of the main concerns in the current poultry industry, causing major economic losses and affecting animal welfare. The most common bone anomalies in the femur are dyschondroplasia, femoral head separation (FHS), and bacterial chondronecrosis with osteomyelitis (BCO), also known as femoral head necrosis (FHN). The present study aimed to identify differentially expressed (DE) genes in the articular cartilage (AC) of normal and FHS-affected broilers by RNA-Seq analysis. In the transcriptome analysis, 12,169 genes were expressed in the femur AC. Of those, 107 genes were DE (FDR < 0.05) between normal and affected chickens, of which 9 were downregulated and 98 were upregulated in the affected broilers. In the gene-set enrichment analysis using the DE genes, 79 biological processes (BP) were identified and were grouped into 12 superclusters. The main BP found were involved in the response to biotic stimulus, gas transport, cellular activation, carbohydrate-derived catabolism, multi-organism regulation, immune system, muscle contraction, multi-organism process, cytolysis, leukocytes and cell adhesion. In this study, the first transcriptome analysis of the broilers femur articular cartilage was performed, and a set of candidate genes (AvBD1, AvBD2, ANK1, EPX, ADA, RHAG) that could trigger changes in the broiler´s femoral growth plate was identified. Moreover, these results could be helpful to better understand FHN in chickens and possibly in humans.

Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies

Background: Hearing loss remains an important global health problem that is potentially addressed through early identification of a genetic etiology, which helps to predict outcomes of hearing rehabilitation such as cochlear implantation and also to mitigate the long-term effects of comorbidities. The identification of variants for hearing loss and detailed descriptions of clinical phenotypes in patients from various populations are needed to improve the utility of clinical genetic screening for hearing loss. Methods: Clinical and exome data from 15 children with hearing loss were reviewed. Standard tools for annotating variants were used and rare, putatively deleterious variants were selected from the exome data. Results: In 15 children, 21 rare damaging variants in 17 genes were identified, including: 14 known hearing loss or neurodevelopmental genes, 11 of which had novel variants; and three candidate genes IST1, CBLN3 and GDPD5, two of which were identified in children with both hearing loss and enlarged vestibular aqueducts. Patients with variants within IST1 and MYO18B had poorer outcomes after cochlear implantation. Conclusion: Our findings highlight the importance of identifying novel variants and genes in ethnic groups that are understudied for hearing loss.

An Fgfr3-activating mutation in immature osteoblasts affects the appendicular and craniofacial skeleton

Achondroplasia (ACH), the most common form of dwarfism is caused by a missense mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3). The resulting increase in FGFR3 signaling perturbs the proliferation and differentiation of chondrocytes (CCs), alters the process of endochondral ossification and thus reduces bone elongation. Increased FGFR3 signaling in osteoblasts (OBs) might also contribute to bone anomalies in ACH. In the present study of a mouse model of ACH, we sought to determine whether or not FGFR3 overactivation in OBs leads to bone modifications. The model carries an Fgfr3 activating mutation (Fgfr3Y367C/+) that accurately mimics ACH; we targeted the mutation to either immature OBs and hypertrophic CCs or to mature OBs by using the Osx-cre and collagen 1α1 (2.3kb-Col1α1)-cre mouse strains, respectively. We observed that Fgfr3 activation in immature OBs and hypertrophic CCs (Osx-Fgfr3) not only perturbed the hypertrophic cells of the growth plate (thus affecting long bone growth) but also led to osteopenia and low cortical thickness in long bones in adult (3-month-old) mice but not in growing (3-week-old) mice. Importantly, craniofacial membranous bone defects were present in the adult mice. In contrast, activation of Fgfr3 in mature OBs (Col1-Fgfr3) had very limited effects on skeletal shape, size and micro-architecture. In vitro, we observed that Fgfr3 activation in immature OBs was associated with low mineralization activity. In conclusion, immature OBs appears to be affected by Fgfr3 overactivation, which might contribute to the bone modifications observed in ACH independently of CCs.

A case report on congenital rubella syndrome

Congenital rubella syndrome (CRS) is a rare illness in infants that result from maternal infection with rubella virus during pregnancy. The case reported is a primigravida at 37.3 weeks of gestation with the complaints of headache, decreased urine output, bilateral pedal edema, puffiness of face and mild hydromnios suggesting pregnancy-induced hypertension (PIH). The previous data showed that the fetus had bone anomalies. Controversially the mother had rubella immune before 12 weeks of pregnancy but the report of nuchal translucency (NT) scan taken during 12 weeks of pregnancy was normal. On history mother denied any evidence of rubella infection during or recently before pregnancy which shows it was asymptomatic. She was treated for PIH. By lower segment caesarean section (LSCS), she delivered an alive boy baby who was acrocyanotic and had deformity in all long bones and enlarged liver. Placenta was found to be abnormal. The baby was under observation and the investigation confirmed CRS. Baby had bradycardia and was intubated on following days and found baby’s vocal cord shape was abnormal. Baby had seizures and could not tolerate weaning from ventilator. Before further investigations, the baby was discharged against medical advice. Though very rare, CRS was found to have many consequences to the fetus. Hence it is significant to rule out rubella infection for mother during or recently before pregnancy as a part of routine antenatal checkup as many of them are asymptomatic. All women should be insisted about getting vaccination for rubella minimum 28 days before planning for conception and should be abandoned for those who were already pregnant.