Search

Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) is an ultra‐rare skeletal dysplasia caused by heterozygous intragenic RUNX2 duplications, comprising either exons 3 to 5 or exons 3 to 6 of RUNX2. In this study, we describe a 14‐year‐old Belgian boy with metaphyseal dysplasia with maxillary hypoplasia but without brachydactyly. Clinical and radiographic examination revealed mild facial dysmorphism, dental anomalies, enlarged clavicles, genua valga and metaphyseal flaring and thin cortices with an osteoporotic skeletal appearance. Exome sequencing led to the identification of a de novo heterozygous tandem duplication within RUNX2, encompassing exons 3 to 7. This duplication is larger than the ones previously reported in MDMHB cases since it extends into the C‐terminal activation domain of RUNX2. We review previously reported cases with MDMHB and highlight the resemblance of this disorder with Pyle disease, which may be explained by intersecting molecular pathways between RUNX2 and sFRP4. This study expands our knowledge on the genotypic and phenotypic characteristics of MDMHB and the role of RUNX2 in rare bone disorders. [ABSTRACT FROM AUTHOR]

RUNX2 (Runt‐related transcription factor 2) is a master regulator of osteoblast differentiation, cartilage and bone development. Pathogenic variants in RUNX2 have been linked to the Cleidocranial dysplasia (CCD), which is characterized by hypoplasia or aplasia of clavicles, delayed fontanelle closure, and dental anomalies. Here, we report 11 unrelated Polish patients with CCD caused by pathogenic alterations located in the Runt domain of RUNX2. In total, we identified eight different intragenic variants, including seven missense and one splicing mutation. Three of them are novel: c.407T>A p.(Leu136Gln), c.480C>G p.(Asn160Lys), c.659C>G p.(Thr220Arg), additional three were not functionally tested: c.391C>T p.(Arg131Cys), c.580+1G>T p.(Lys195_Arg229del), c.652A>G p.(Lys218Glu), and the remaining two: c.568C>T p.(Arg190Trp), c.673C>T p.(Arg225Trp) were previously reported and characterized. The performed transactivation and localization studies provide evidence of decreased transcriptional activity of RUNX2 due to mutations targeting the Runt domain and prove that impairment of nuclear localization signal (NLS) affects the subcellular localization of the protein. Presented data show that pathogenic variants discovered in our patients have a detrimental effect on RUNX2, triggering the CCD phenotype. [ABSTRACT FROM AUTHOR]

Depression, anxiety, and aggression accompany neuropathic pain. Effective treatment of these comorbidities enhances the outcomes of pain management. Therefore, the study was designed to analyze the relationship between the intensity of depression, anxiety, and aggression and the pharmacotherapy applied in the daily practice of treating neuropathic pain. The aim of the study was to evaluate the frequency of using antidepressants (ADs), benzodiazepine anxiolytics (BDAs), and hypnotics, and the influence of administering these on the intensity of depression, anxiety, and aggression in patients diagnosed with neuropathic pain. A multi-center survey was conducted among 421 patients. An evaluation of the severity of depression, anxiety, and aggression was made using the Hospital Anxiety and Depression Scale—Modified Version (HADS-M). Among the patients treated due to neuropathic pain, ADs are used much more often than BDAs and hypnotics. Depression was well controlled, while anxiety was identified as a possible uncontrolled therapeutic problem in these patients, despite the correlation between the frequency of AD and hypnotics usage and the severity of anxiety. We also found that women show a higher level of intensity in both anxiety and depression, but this does not influence the frequency of their being administered ADs, BDAs, and hypnotics. [ABSTRACT FROM AUTHOR]