Identification of de novo EP300 and PLAU variants in a patient with Rubinstein–Taybi syndrome-related arterial vasculopathy and skeletal anomaly

Rubinstein–Taybi syndrome (RSTS) is a human genetic disorder characterized by distinctive craniofacial features, broad thumbs and halluces, and intellectual disability. Mutations in the CREB binding protein (CREBBP) and E1A binding protein p300 (EP300) are the known causes of RSTS disease. EP300 regulates transcription via chromatin remodeling and plays an important role in cell proliferation and differentiation. Plasminogen activator, urokinase (PLAU) encodes a serine protease that converts plasminogen to plasmin and is involved in several biological processes such as the proteolysis of extracellular matrix-remodeling proteins and the promotion of vascular permeability and angiogenesis. Recently, we discovered a patient who presented with RSTS-related skeletal anomaly and peripheral arterial vasculopathy. To investigate the genetic cause of the disease, we performed trio whole genome sequencing of the genomic DNA from the proband and the proband’s parents. We identified two de novo variants coined c.1760T>G (p.Leu587Arg) and c.664G>A (p.Ala222Thr) in EP300 and PLAU, respectively. Furthermore, functional loss of EP300a and PLAUb in zebrafish synergistically affected the intersegmental vessel formation and resulted in the vascular occlusion phenotype. Therefore, we hypothesize that the de novo EP300 variant may have caused RSTS, while both the identified EP300 and PLAU variants may have contributed to the patient’s vascular phenotype.

Is there a relationship between transverse maxillary deficiency and sella turcica: A cephalometric analysis study?

Objectives: The aim of this study was to investigate the dimensions and morphological variations of sella turcica and to test whether a relationship exists between sella turcica and transverse maxillary deficiency. Materials and Methods: The cephalometric radiographs of patients older than 17.99 years, which have been taken before the orthodontic treatment, and patient records were analyzed to investigate sella turcica dimensional and morphological analysis. Linear measurements of sella are as follows sella length, sella width, sellar area, sella height anterior, posterior, and median. The sella turcica morphological shape analysis was performed into six groups (normal sella turcica, oblique anterior wall, sella turcica bridge, double contour of floor, irregularities of the posterior part of the dorsum sella, and pyramidal shape of the dorsum sella). The width of the maxillary arch is measured by the digital caliper. Male participants with a maxillary width of less than 30.8 mm and a maxillary width of less than 31.1 mm in female patients in the first molar region were determined as a transverse maxillary deficiency. The mean dimensions of sella turcica and the relationship between cases with transverse maxillary deficiency and non-skeletal anomaly were compared using independent samples t-tests. The transverse maxillary deficiency and the sellar morphology relationship were compared using Chi-square test. Post hoc multiple comparisons and analyzes were performed at 95% confidence interval by Bonferroni correction. Results: The sella length measurements yielded higher values among the patients with transverse maxillary deficiency (P < 0.05). The normal sella morphology had quantitative superiority in patients without skeletal anomaly in comparison with transverse maxillary deficiency cases (P < 0.05). It was observed that the sella turcica bridge had a statistically superiority in patients with transverse maxillary deficiency (P < 0.05). Conclusion: The increased sellar measurement and sella turcica bridging, may provide knowledge about possible transverse maxillary deficiency.

Rare congenital anomaly among population of the Migration Period (based on excavations in the Eastern Aral region)

This paper aims to introduce into scientific discourse the information on unique pathological features ob-served in the individuals of the Jetyasar archaeological Culture buried in the necropolis of Altyn-Asar 4. In the course of examining the extensive paleoanthropological collection of the human remains (more than 600 individu-als) of the Jetyasar Culture from the excavations of the Kwarism Expedition of the USSR Academy of Sciences in the Eastern Aral region, three cases of a rare skeletal anomaly have been discovered, which is manifested by forearm synostosis. In the modern medical literature, slightly more than 350 of such cases have been reported. Radioulnar synostosis severely restricts the movements of pronation and supination (ulnar adduction and devia-tion) by fixing the radial and ulnar bones in a single possible position. Methods of differential diagnostics have been used in description of the skeletal features, alongside the digital micro-focal radiography and microtomogra-phy. There is evidence to suggest congenital form of the above maldevelopment in the Early Medieval Eastern Aral region. Although this pathology may lead to partial disability, its bearers, attributed in the context of the Je-tyasar Culture, were fully socially adapted and each of them had sufficiently long life by the expectancy of the time. Radioulnar stenosis has been identified in a 30–34-year-old male from the grave no. 326.1 of the burial ground of Altyn-Asar 4l and in two 25–29-year-old females from the burial ground of Altyn-Asar 4r (graves nos. 345 and 454.2). The former case is the earlier one, no later than the 4th c. AD according to the archaeological data. By the context of this multiple-body burial, this individual was married and might have carried the congenital pathology onto his descendants. The burial of the married woman with the same pathology in the burial ground of Altyn-Asar 4r (no. 454.2) was made later in the last third of the AD 6th c., according to the planigraphy and AMS radiocarbon date for a neighbouring kurgan. The latest grave no. 345 of the same burial ground, according to the results of the direct dating (UGAMS#43733 1450  20 years BP), is distant in time from the previous case by one generation and corresponds to the beginning of the 7th c.

An unusual association of ulnar hemimelia with mesoaxial synostotic syndactyly

Ulnar hemimelia, also referred to as post-axial longitudinal deficiency of the upper limb, is a very rare skeletal anomaly characterized by the partial or complete absence of the ulna. The majority of the reported cases are sporadic and more common in males. The disorder is mostly unilateral, right-sided and incomplete. A slight shortening of the forearm, radial bowing and ulnar-sided hand drift are the anomalies which often accompany ulnar hemimelia. Ulnar hemimelia may also be seen in association with complex wrist and hand anomalies. The absence of post-axial metacarpal and digital bones are frequent findings in patients with this rare disorder. Cases with additional digital abnormalities such as post-axial syndactyly and camptodactyly are also present in the literature. However, a case of ulnar hemimelia in association with mesoaxial synostotic syndactyly has never been reported to date.

Cervical scoliosis and torticollis: a novel skeletal anomaly in broiler chickens

Background Among the most prominent health problems marring the global poultry industry for several decades are skeletal abnormalities. The aim of this study was to investigate a recent emergence of a novel form of skeletal deformity affecting cervical spine in broiler chickens. This work presents the natural history of this newly emerging skeletal anomaly along with long term observations of epidemiological trends in commercial broiler flocks, and clinical and pathological features. Results In distinction from other forms of skeletal deformities commonly reported in broiler chickens, this new form of cervical spine anomaly have been observed in newly hatched chicks and in fully developed embryos that died in the shell. On clinical and post mortem examination this condition presents characteristic features consistent with congenital cervical scoliosis and torticollis (CCST). The pathogenesis of CCST appears to be linked to pathological remodeling of the cervical vertebrae bone associated with excessive activity of osteoclasts. Long term observations indicate that the incidence of CCST showed increasing epidemiological trends over time. More recently CCST has been observed in newly hatched chicks with incidence ranging from 0.1 to > 1%, and in fully developed embryos that failed to hatch about 4 to 5%. Conclusions The increasing trends in incidence of CCST in commercial broiler flocks are of concern from an economic perspective, and also represent a very specific and important aspect of animal welfare.

Right Ventricular Compression Mimicking Brugada-Like Electrocardiogram in a Patient with Recurrent Pectus Excavatum

Pectus excavatum (PE), the most common skeletal anomaly of chest wall, sometimes requires a surgical correction but recurrent PE is not uncommon. PE usually has a benign course; however, this chest deformity may be associated with symptomatic tachyarrhythmias due to mechanical compression. We report a case of a patient with recurrent PE after surgical correction presenting with palpitation and electrocardiogram (ECG) showing ST-segment elevation on the right precordial leads, which could be mistaken for a Brugada syndrome (BrS).

Multiple Bony Injuries on Bone Scan in a Case of Unsuspected Child Abuse

This case is described of an eleven-month-old infant with lower limbs swelling and the left elbow skeletal malformation following a fall. The radionuclide bone scan was performed to exclude bone infection or congenital skeletal anomaly. The images unexpectedly showed multiple increased radioactive foci throughout the whole body. It was a strong probability of child abuse. All lesions are readily apparent on the following plain film radiographs and MRI.