Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is caused by a duplication in RUNX2.

Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly (MDMHB) is an autosomal-dominant bone dysplasia characterized by metaphyseal flaring of long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, variable brachydactyly, and dystrophic teeth. We performed genome-wide SNP genotyping in five affected and four unaffected members of an extended family with MDMHB. Analysis for copy-number variations revealed that a 105 kb duplication within RUNX2 segregated with the MDMHB phenotype in a region with maximum linkage. Real-time PCR for copy-number variation in genomic DNA in eight samples, as well as sequence analysis of fibroblast cDNA from one subject with MDMHB confirmed that affected family members were heterozygous for the presence of an intragenic duplication encompassing exons 3 to 5 of RUNX2. These three exons code for the Q/A domain and the functionally essential DNA-binding runt domain of RUNX2. Transfection studies with murine Runx2 cDNA showed that cellular levels of mutated RUNX2 were markedly higher than those of wild-type RUNX2, suggesting that the RUNX2 duplication found in individuals with MDMHB leads to a gain of function. Until now, only loss-of-function mutations have been detected in RUNX2; the present report associates an apparent gain-of-function alteration of RUNX2 function with a distinct rare disease.

Prenatal diagnosis and physical model reconstruction of agnathia-otocephaly with limb deformities (absent ulna, fibula and digits) following maternal exposure to oxymetazoline in the first trimester.

Agnathia-otocephaly or agnathia-sinotia-microstomy syndrome is the most severe malformation affecting the first branchial arch. It is a rare congenital anomaly characterized by absence of the lower jaw and abnormal ear positioning. Prenatal diagnosis is possible on conventional 2-D ultrasound in the second trimester. Three-dimensional ultrasound enhances detection of abnormal facial phenotype, especially in surface rendering mode. In addition, 3-D volume datasets are used to produce a physical model of the anomaly. We present a case of second trimester ultrasound diagnosis of agnathia-otocephaly associated with limb deformities. A physical model produced using 3-D ultrasound volume datasets facilitated better understanding of this congenital malformation, and improvement of parental counselling and management by the multispecialist team.

Hyperspectral imaging with deep learning for quantification of tissue hemoglobin, melanin, and scattering.

Significance: Hyperspectral cameras capture spectral information at each pixel in an image. Acquired spectra can be analyzed to estimate quantities of absorbing and scattering components, but the use of traditional fitting algorithms over megapixel images can be computationally intensive. Deep learning algorithms can be trained to rapidly analyze spectral data and can potentially process hyperspectral camera data in real time. Aim: A hyperspectral camera was used to capture 1216 × 1936 pixel wide-field reflectance images of in vivo human tissue at 205 wavelength bands from 420 to 830 nm. Approach: The optical properties of oxyhemoglobin, deoxyhemoglobin, melanin, and scattering were used with multi-layer Monte Carlo models to generate simulated diffuse reflectance spectra for 24,000 random combinations of physiologically relevant tissue components. These spectra were then used to train an artificial neural network (ANN) to predict tissue component concentrations from an input reflectance spectrum. Results: The ANN achieved low root mean square errors in a test set of 6000 independent simulated diffuse reflectance spectra while calculating concentration values more than 4000× faster than a conventional iterative least squares approach. Conclusions: In vivo finger occlusion and gingival abrasion studies demonstrate the ability of this approach to rapidly generate high-resolution images of tissue component concentrations from a hyperspectral dataset acquired from human subjects.

The use of cone beam computed tomography for the assessment of trichorhinophalangeal syndrome, type I - a case report.

Trichorhinophalangeal syndrome type I is a rare autosomal dominant disorder characterized by cone-shaped epiphysis, sparse fine hair, pear-shaped nose and variable growth retardation. The typical craniofacial features include thin upper lip, elongated philtrum, large outstanding ears, shortened posterior facial height associated with short mandibular ramus and reduced and superiorly deflected posterior cranial base. This report describes a 17-year-old male patient with trichorhinophalangeal syndrome type I and a detailed description of the craniofacial radiographic findings, including the use of cone beam computed tomography images for determination of the airway and temporomandibular joint discrepancies.

Clinical Applications of Meshed Multilayered Anatomical Models by Low-Cost Three-Dimensional Printer.

SUMMARY: In recent years, even low-cost fused deposition modeling-type three-dimensional printers can be used to create a three-dimensional model with few errors. The authors devised a method to create a three-dimensional multilayered anatomical model at a lower cost and more easily than with established methods, by using a meshlike structure as the surface layer. Fused deposition modeling-type three-dimensional printers were used, with opaque polylactide filament for material. Using the three-dimensional data-editing software Blender (Blender Foundation, www.blender.org) and Instant Meshes (Jakob et al., https://igl.ethz.ch/projects/instant-meshes/) together, the body surface data were converted into a meshlike structure while retaining its overall shape. The meshed data were printed together with other data (nonmeshed) or printed separately. In each case, the multilayer model in which the layer of the body surface was meshed could be output without any trouble. It was possible to grasp the positional relationship between the body surface and the deep target, and it was clinically useful. The total work time for preparation and processing of three-dimensional data ranged from 1 hour to several hours, depending on the case, but the work time required for converting into a meshlike shape was about 10 minutes in all cases. The filament cost was $2 to $8. In conclusion, the authors devised a method to create a three-dimensional multilayered anatomical model to easily visualize positional relationships within the structure by converting the surface layer into a meshlike structure. This method is easy to adopt, regardless of the available facilities and economic environment, and has broad applications.

Radiographic 2D:4D index in females: no relation to anthropometric, behavioural, nutritional, health-related, occupational or fertility variables.

BACKGROUND: The ratio of index finger to ring finger length (2D:4D index) may be an indicator of gonadal hormone exposure, because the differentiation of gonads, fingers and toes is influenced by the same HOXA and HOHD genes. Some previous studies have found significant associations between the 2D:4D index and sexual, psychological or behavioural variables. We studied the usability of the radiographic 2D:4D index as a potential predictor of several features in a large female sample. METHODS: 271 female dentists and 219 teachers (age 45 - 63 years) had their hands radiographed and their right 2nd and 4th fingers measured from the base of the bony proximal phalanxes to the tip of the distal phalanxes to define the radiographic 2D:4D index. The study subjects were classified into two distinctly separate clusters (by using cluster analysis with the K-means algorithm) in each of the following dimensions: anthropometric (including four items), behavioural (five items), nutritional (five items), health-related (seven items), occupational (Karasek job control and job demand scores) and fertility (four items). RESULTS: The radiographic 2D:4D index ranged from 0.845 to 0.981 (mean 0.925, SD 0.021). The intraclass correlation between three radiographers' measurements (31 cases) was 0.971. No differences concerning the 2D:4D index were found between clusters 1 and 2 in any studied dimension, nor did any of the items in clusters have relations with the 2D:4D index when tested separately with bivariate tests. CONCLUSION: Despite the ideal set-up of the measuring possibilities in a relatively large radiographic material the variables currently studied were not dependent on the length of finger bones. It can therefore be questioned whether any real associations between the bony 2D:4D index in adult life and (direct or indirect) hormone dependent effects exist. There may be a publication bias explaining that mostly positive findings have been the previously reported. However, the associations of the 2D:4D index with various features, if present, may be related to the soft parts of fingers rather than to the length of bones.

Photon-counting hexagonal pixel array CdTe detector: Spatial resolution characteristics for image-guided interventional applications.

PURPOSE: High-resolution, photon-counting, energy-resolved detector with fast-framing capability can facilitate simultaneous acquisition of precontrast and postcontrast images for subtraction angiography without pixel registration artifacts and can facilitate high-resolution real-time imaging during image-guided interventions. Hence, this study was conducted to determine the spatial resolution characteristics of a hexagonal pixel array photon-counting cadmium telluride (CdTe) detector. METHODS: A 650 µm thick CdTe Schottky photon-counting detector capable of concurrently acquiring up to two energy-windowed images was operated in a single energy-window mode to include photons of 10 keV or higher. The detector had hexagonal pixels with apothem of 30 µm resulting in pixel pitch of 60 and 51.96 µm along the two orthogonal directions. The detector was characterized at IEC-RQA5 spectral conditions. Linear response of the detector was determined over the air kerma rate relevant to image-guided interventional procedures ranging from 1.3 nGy/frame to 91.4 µGy/frame. Presampled modulation transfer was determined using a tungsten edge test device. The edge-spread function and the finely sampled line spread function accounted for hexagonal sampling, from which the presampled modulation transfer function (MTF) was determined. Since detectors with hexagonal pixels require resampling to square pixels for distortion-free display, the optimal square pixel size was determined by minimizing the root-mean-squared-error of the aperture functions for the square and hexagonal pixels up to the Nyquist limit. RESULTS: At Nyquist frequencies of 8.33 and 9.62 cycles/mm along the apothem and orthogonal to the apothem directions, the modulation factors were 0.397 and 0.228, respectively. For the corresponding axis, the limiting resolution defined as 10% MTF occurred at 13.3 and 12 cycles/mm, respectively. Evaluation of the aperture functions yielded an optimal square pixel size of 54 µm. After resampling to 54 µm square pixels using trilinear interpolation, the presampled MTF at Nyquist frequency of 9.26 cycles/mm was 0.29 and 0.24 along the orthogonal directions and the limiting resolution (10% MTF) occurred at approximately 12 cycles/mm. Visual analysis of a bar pattern image showed the ability to resolve close to 12 line-pairs/mm and qualitative evaluation of a neurovascular nitinol-stent showed the ability to visualize its struts at clinically relevant conditions. CONCLUSIONS: Hexagonal pixel array photon-counting CdTe detector provides high spatial resolution in single-photon counting mode. After resampling to optimal square pixel size for distortion-free display, the spatial resolution is preserved. The dual-energy capabilities of the detector could allow for artifact-free subtraction angiography and basis material decomposition. The proposed high-resolution photon-counting detector with energy-resolving capability can be of importance for several image-guided interventional procedures as well as for pediatric applications.

Hajdu--Cheney syndrome: evolution of phenotype and clinical problems.

Hajdu-Cheney syndrome is a rare, autosomal dominant disorder comprising acroosteolysis of the distal phalanges with associated digital abnormalities, distinctive craniofacial and skull changes, dental anomalies, and proportionate short stature. The clinical and radiologic characteristics of Hajdu-Cheney syndrome develop and progress with age. Many of the medical problems that arise in this syndrome cluster in specific age ranges. Case reports of six affected individuals in two additional families and a summary of the English literature is presented with emphasis on the changing physical findings and medical sequelae over time.

Zimmermann-Laband syndrome in an adult. Long-term follow-up of a patient with vascular and cardiac complications.

Zimmermann-Laband syndrome (ZLS) is characterised by findings of coarse facial appearance, hepatosplenomegaly, and hirsutism often first observed in infancy, followed by the evolution during childhood of gingival fibromatosis, small joint hyperextensibility, and hypoplasia of the finger- and toenails. Intellectual deficit is variable. Some of these findings are suggestive of a storage disorder, but no biochemical defect has been identified. We report on a four decade follow-up of a male with ZLS who developed a cardiomyopathy and dilatation of the aortic root and arch, anomalies hitherto undescribed in this syndrome.

Unique case of growth hormone (GH) deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.

A 43-year-old female was admitted to our hospital for polydipsia and hyperglycemia. She had total blindness and globes were not recognized by inspection, indicating clinical anophthalmia. Physical examination revealed short stature, obesity, prematurely gray hair, shortness of fingers and toes, syndactyly, and multiple dental caries. Laboratory examination showed hyperglycemia, increased glycosilated hemoglobin (HbA1c) and insulin resistance on euglycemic glucose clamp. Blunted growth hormone (GH) secretion was shown in response to insulin-induced hypoglycemia, arginine infusion, and GH-releasing hormone (GHRH) loading test, and in 24 h spontaneous GH profile. Magnetic resonance imaging (MRI) and computed tomography (CT) showed dysostosis of orbit, defect of optic nerve, enlarged suprasellar cistern, and prolonged pituitary stalk. This may be the first report of a unique case with GH deficiency accompanied by clinical anophthalmia, hypoplastic orbits, digital dysplasia, short stature, obesity, and diabetes mellitus.

[Reparative giant-cell granuloma of the extremities]. / Das reparative Riesenzellgranulom der Extremitäten.

Giant-cell reparative granulomas are observed not infrequently in the mandible as sharply demarcated osteolytic lesions. On the other hand, these tumour-like lesions occurring in short tubular bones are rarely reported in the literature and, so far, only 27 cases have been described. We have records of five cases in the Westphalian Bone Tumour Register. The actual occurrence is probably greater if one assumes that the lesion is caused by an intra-osseous bleeding. This pathogenic mechanism is supported by histological evidence.

Syndromic dystelephalangy.

We report an 8-year-old boy with a distinctive facial phenotype, deformities of fingers and toes and limitation of knee movement of unknown etiology. He had a round face, a long nose, a thin upper lip, a small mouth and micrognathia. In spite of microcephaly and retarded speech development secondary to hearing loss his mental development was within normal limits. The most distinctive radiographic abnormality was hypoplasia of the distal end of the middle phalanges with radial deviation of the distal phalanges.

"Uneasy lies the hand in which rests the crown" an unusual foreign body following a punch injury.

A case of cellulitis of the hand resulting from embedding of a dental crown following a punch injury is described. This report emphasises the need for X-ray imaging in all cases of penetrating hand trauma, particularly when the history is vague, and also the difficulty in using metronidazole in alcoholic patients.

[Trichorhinophalangeal syndrome. Apropos of 4 cases discovered in adults]. / Syndrome tricho-rhino-phalangien. A propos de quatre cas découverts chez l'adulte.

Of four adult patients with the trichorhinophalangeal syndrome, 3 were from one family, one had associated major femoral trochlear dysplasia and bilateral mandibular condyle dysplasia, and another a bilateral coxa plana.

The developmental stages of the middle phalanx of the third finger (MP3): a sole indicator in assessing the skeletal maturity?

Assessment of skeletal maturity is an integral part of interceptive diagnosis and treatment planning. The present day methods of skeletal maturity assessment like the hand-wrist radiographs or cervical vertebrae radiographs are expensive, require elaborate equipment and accounts for high radiation exposure, especially for growing children. The present study was thus undertaken to provide a simple and practical method of skeletal maturity assessment using the developmental stages of the middle phalanx of the third finger (MP3) as seen on an IOPA film taken using a standard dental x-ray machine. The results of the study showed that this simple method was highly reliable and could be used as an alternative method to assess the skeletal maturity of growing children.

[Roentgen image of the hand as a principle for age determination in adolescents]. / Das Röntgenbild der Hand als eine Grundlage der Altersschätzung bei Jugendlichen.

Determination of age can be necessary in cases of juvenile offenders. We studied the relation between the skeletal development of the hand and wrist and the age, using diagnostic methods of orthodontics. An evaluation of 1109 X-ray pictures of the hand and wrist of boys and girls with an age from 9-18 years showed that there is a stochastic correlation between age and certain stages of skeletal development. Skeletal development is influenced by sex and ethnological factors.

Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly in a Finnish woman: first confirmation of a duplication in RUNX2 as pathogenic variant.

Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly (MDMHB) is an autosomal-dominant bone dysplasia that until now has only been reported in French Canadian individuals. We have recently identified an intragenic duplication in RUNX2, encompassing exons 3 to 5, as a cause of MDMHB in French Canadian families. Here we describe a 20-year-old Finnish woman who had typical clinical and radiological signs of MDMHB, the first reported individual with MDMHB who is not of French-Canadian origin. Copy number variant assays based on quantitative PCR of genomic DNA showed the presence of three copies within a part of RUNX2. Sequencing RUNX2 cDNA from the skin fibroblasts revealed a duplication of exons 3 to 5. The results demonstrated that the intronic breakpoints of the duplication differed from those previously found in the French Canadian family, but that the consequences on RUNX2 transcript were identical. These findings demonstrate that the MDMHB phenotype results from an intragenic duplication of RUNX2 exons 3 to 5 also outside of the community where the disorder was first identified.