SATB2‐associated syndrome (SAS) is a rare disorder characterized by developmental delay, behavioral problems, and craniofacial anomalies in particular dental and palatal abnormalities. We describe ...the clinical course, genetic and autopsy findings in a Chinese boy with global developmental delay, hypotonia, epilepsy, recurrent fractures and osteopenia. Brain magnetic resonance imaging showed pachygyria, white matter hypoplasia and hypogenesis of the corpus callosum. Whole‐exome sequencing identified a novel heterozygous missense variant c.1555G>A p.(Glu519Lys) in the SATB2 gene. Unfortunately, he died at 26 months of bronchiolitis and pneumonia. Autopsy revealed pachygyria which was more severe anteriorly, dilated lateral and third ventricles and partial agenesis of the corpus callosum. Histology showed features compatible with two‐layered lissencephaly. The bone showed disordered lamination and bone matrix. Although SATB2 has been shown to be involved in the regulation of neuronal migration in the developing brain, lissencephaly has not been reported so far. This could represent a more severe phenotype of SAS.
Brown Root Rot Disease (BRRD) is one of the most devastating urban tree diseases in tropical and subtropical areas, including Hong Kong. It can result in tree death in a few months and is difficult ...to detect in the early stages of development. Fungal isolation and PCR methods are currently the most widely adopted methods to diagnose the disease. However, they are both time and technically demanding. Loop-mediated isothermal amplification (LAMP) is a superior molecular-based diagnostic method with great specificity, accessibility, and effectivity. In this study, 15 BRRD-positive and 15 BRRD-negative trees were sampled from 19 roadside slopes in Hong Kong from the end of 2020 to the middle of 2021. The wood tissues were isolated and cultivated in PN3 and PDA agars for the disease diagnosis. The mycelium samples in PDA were directly conducted in LAMP kits (mLAMP) to substitute the purified DNA materials. Wood tissues were also used in LAMP kits (wLAMP) as impurified and highly contaminated samples. The results of mLAMP and wLAMP were compared with the results of isolation to evaluate the specificity and sensitivity of LAMP method. The results showed that mLAMP had 100% sensitivity and 73.3% specificity. For wLAMP, both the sensitivity and specificity were 73.3%. For symptomless trees, 85.7% and 64.3% congruencies were found in mLAMP and wLAMP, respectively. Based on the results of this study, the co-application of LAMP in the current tree management work was also discussed. We envisaged LAMP is a sensitive, prompt, and user-friendly method to diagnose BRRD and it could favor the BRRD diagnosis in fields by accelerating and promoting large-scale screening.
Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we ...report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.
We present the clinical course of a 4-year-old girl with neurofibromatosis type 1-associated, unresectable, symptomatic urinary bladder ganglioneuroma. She was initially trialed on sirolimus without ...response and subsequently responded to MEK inhibitor trametinib, with improvement clinically and radiographically over 10 months. This report broadens the repertoire of therapeutic strategies for MEK inhibition in diseases related to the MAPK pathway.
Background
Transplant‐associated thrombotic microangiopathy (TA‐TMA) is an under‐recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had ...increased awareness in recent years. This report summarizes the demographics and outcomes of pediatric TA‐TMA in Hong Kong.
Methods
All patients aged below 18 years who underwent HSCT in the Hong Kong Children's Hospital and were diagnosed to have TA‐TMA during the 2‐year period from April 1, 2019 to March 31, 2021 were included.
Results
A total of 73 transplants (51 allogeneic and 22 autologous) in 63 patients had been performed. Six patients (four males and two females) developed TA‐TMA at a median duration of 2.5 months post‐HSCT. The incidence rate was 9.52%. Of the six TA‐TMA patients, five underwent allogenic one underwent autologous HSCT, respectively. Three of them were histologically proven. All four patients with cyclosporine had stopped the drug once TA‐TMA was suspected. Median six doses of eculizumab were administered to five out of six patients. Three patients died (two due to fungal infection and one due to acute‐on‐chronic renal failure) within 3 months upon diagnosis of TA‐TMA. Among three survivors, two stabilized with mild stage 2 chronic kidney disease (CKD) while the other suffered from stage 5 end‐stage CKD requiring lifelong dialysis.
Conclusion
In conclusion, recognition and diagnosis of TA‐TMA are challenging. Early recognition and prompt administration of complement blockage with eculizumab may be beneficial in selected cases. Further prospective research studies are recommended to improve the management and outcomes of TA‐TMA.
We report an unusual case of a pelvic extraovarian moderately differentiated Sertoli-Leydig cell tumor arising in a 4-yr-old female. The tumor contained a DICER1 pathogenic variant which was absent ...in the germline ruling out DICER1 syndrome. In reporting this case, we discuss the differential diagnosis and possible histogenesis and review reported cases of extraovarian Sertoli-Leydig cell tumor.
Severe acute respiratory syndrome (SARS) has become a global public health emergency.
To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of ...mortality.
Retrospective cohort study.
Quarantine hospital for patients with SARS in Hong Kong.
267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS.
Clinical, laboratory, and radiographic measures; 3-month mortality rate.
According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 CI, 2.30 to 11.31; P < 0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 CI, 1.03 to 4.71; P = 0.04) were independent predictors of mortality.
Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.
Summary The viral dissemination in a patient with avian influenza A subtype H5N1 infection was retrospectively studied by the immunohistochemical localization of viral nucleoprotein antigen. The ...pathology was marked by diffuse alveolar damage, lymphoid depletion, and reactive hemophagocytic syndrome. Besides the lung and the upper respiratory tract, viral antigen was detected in the small and large intestinal epithelial cells, hematopoietic cells in the bone marrow, glial cells and neurons of the brain, and lymphocytes. The results confirmed that H5N1 virus disseminated to multiple organs beyond the respiratory system. However, specific pathological changes were noted in the respiratory system only, and productive viral replication confirmed by culture was noted only in the lung. More postmortem studies are needed to elucidate the pathogenesis of this highly fatal zoonotic disease.
The pathology of 2 zoonotic human viral infections that recently emerged, severe acute respiratory syndrome (SARS) due to coronavirus (SARS-CoV) and avian influenza A subtype H5N1, is reviewed and ...compared based on the literature and the cases examined by the authors. Pneumocytes are the primary target of infection resulting in diffuse alveolar damage. Systemic cytokine activation results in hemophagocytic syndrome, lymphoid depletion, and skeletal muscle fiber necrosis. Severe acute respiratory syndrome induces a more fibrocellular intra-alveolar organization with a “bronchiolitis obliterans organizing pneumonia”–like pattern and presence of multinucleated histiocytes and pneumocytes. H5N1 causes a more fulminant and necrotizing diffuse alveolar damage with patchy and interstitial paucicellular fibrosis. Severe acute respiratory syndrome associated coronavirus persists in the lung up to the second month, whereas H5N1 persists in the lung up to the third week. Severe acute respiratory syndrome associated coronavirus disseminates to blood, urine, feces, gastrointestinal tract, and liver. There is recent report of possible cerebral involvement by H5N1 and its isolation in the blood, gastrointestinal tract, and cerebrospinal fluid. More pathologic studies are urgently needed.
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