SBIDDS Syndrome: A New Spoke of the Epigenetic Machinery Wheel.

Introduction: Mendelian disorders of the epigenetic machinery are a growing group of disorders exhibiting several overlapping clinical features that are probably due to common abnormalities at the epigenomic level, which lead to downstream convergence at the transcriptomic level. Case presentation: Here, we report a new case of short stature, brachydactyly, intellectual developmental disability, and seizures (SBIDDS) syndrome with a severe ocular phenotype and hypogonadism. Conclusion: Similarities and connections with other mendelian disorders of the epigenetic machinery are highlighted, confirming SBIDDS' enrolment as a new spoke of the epigenetic machinery wheel.

Let Time Teach You: A Case Report of a Double Diagnosis of 17P Duplication and Ehlers-Danlos Syndrome.

Kyphoscoliotic Ehlers-Danlos syndrome and 17p13.3 microduplication share multiple clinical features such as muscle hypotonia, cleft palate, and growth impairment. This paper describes a patient who was first diagnosed with the duplication and a decade later also with FKBP14-kEDS. The latter was initially overlooked due to the pathogenic significance attributed to the duplication and to the fact that, at the time of the first diagnosis, this specific form of kEDS had yet to be discovered. The patient's progressive kyphoscoliosis and severe joint laxity were the clinical features that prompted the patient's physiatrist to reassess the genetic work-up. This extreme latency caused inaccurate management in the patient's follow-up program, which ultimately may have resulted in preventable clinical complications. This report underlines the importance of remaining up-to-date with patient status, reviewing old cases, and relying on specialist advice to reach a correct diagnosis.

From clinical to molecular diagnosis: relevance of diagnostic strategy in two cases of branchio-oto-renal syndrome - case report.

BACKGROUND: Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by deafness, branchiogenic malformations and renal abnormalities. Pathogenic variants in EYA1, SIX1 and SIX5 genes cause almost half of cases; copy number variants (CNV) and complex genomic rearrangements have been revealed in about 20% of patients, but they are not routinely and commonly included in the diagnostic work-up. CASE PRESENTATION: We report two unrelated patients with BOR syndrome clinical features, negative sequencing for BOR genes and the identification of a 2.65 Mb 8q13.2-13.3 microdeletion. CONCLUSIONS: We highlight the value of CNV analyses in high level of suspicion for BOR syndrome but negative sequencing for BOR genes and we propose an innovative diagnostic flow-chart to increase current detection rate. Our report confirms a mechanism of non-allelic homologous recombination as causing this recurrent 8q13.2-13.3 microdeletion. Moreover, considering the role of PRDM14 and NCOA2 genes, both involved in regulation of fertility and deleted in our patients, we suggest the necessity of a longer follow-up to monitor fertility issues or additional clinical findings.

Has Otitis Media Disappeared during COVID-19 Pandemic? A Fortuitus Effect of Domestic Confinement.

BACKGROUND: To measure patient flow at our Pediatric Emergency Department (PED) during the Italian lockdown, with particular care in terms of otolaryngological (ENT)-related diagnoses. METHODS: A retrospective evaluation of electronic charts of children admitted to our PED in the City Center of Milan (Italy) for any disease. The outcome was to compare distribution of diagnoses performed at our PED during 21 February-3 May 2019 (period 1) to 21 February-3 May 2020 (period 2). RESULTS: A total of 4538 children were evaluated during period 1 compared to 1310 during period 2. A statistically significant overall effect on diagnosis between the study periods was attested (p-value < 0.001; pseudo R2 = 0.010), ENT-related diagnoses being more frequently documented in period 1 (80.4% vs. 19.5%; p-value < 0.001), as well as those related to middle ear infections (92.8% vs. 7.2%; p-value < 0.001). Non-complicated acute otitis media more frequently occurred in period 1 (92.0% vs. 8.0%; p-value < 0.001); no significant difference in the number of complicated middle ear infections occurred (95.8% vs. 4.2%). CONCLUSIONS: The exceptional circumstances of the Italian lockdown resulted in a significant decrease in patients' attendance to our PED, especially when considering diagnoses related to any ENT disorder, middle ear disease, and non-complicated middle ear infection.

Pediatric Septic Arthritis of the Knee Due to a Multi-Sensitive Streptococcus pyogenes Strain Responsive to Clindamycin-A Case Report.

Septic arthritis is an inflammatory process usually generated by a bacterial infection. The knee is one of the most frequently involved joints. The etiology varies depending on age, and hematogenous spread remains the primary cause in children. Herein, we report a case of a previously healthy three-year-old female who was referred to our institution for acute swelling of her right knee. After a clinical and radiological diagnosis of septic arthritis, an empirical treatment with a combination of cefotaxime and clindamycin was initiated. The isolation of a multi-sensitive Streptococcus pyogenes strain from the joint's effusion prompted the discontinuation of clindamycin and the usage of cefotaxime alone. One week later, an ultrasound was executed due to worsening in the patient's clinical conditions, and an organized corpuscular intra-articular effusion with diffuse synovial thickening was revealed. Cefotaxime was therefore replaced with clindamycin, which improved the symptoms. Despite the antibiotic sensitivity test having revealed a microorganism with sensitivity to both cephalosporin and clindamycin, clinical resistance to cefotaxime was encountered and a shift in the antimicrobial treatment was necessary to ensure a full recovery. This case study confirms that an antibiotic regimen based solely on a susceptibility test may be ineffective for such cases.

Pediatric otogenic cerebral venous sinus thrombosis: a case report and a literature review.

BACKGROUND: Cerebral venous sinus thrombosis in children is a rare but potentially fatal complication of acute mastoiditis, one of the most common pediatric infectious diseases. Due to its subtle clinical presentation, suspicion is essential for a prompt diagnosis and appropriate management. Unfortunately, no standard treatment options are available. To discuss the possible clinical presentation, microbiology, and management, we here report the case of a child with otogenic cerebral venous sinus thrombosis and perform a literature review starting from 2011. CASE PRESENTATION: The child, a 10-months-old male, presented clinical signs of right acute otitis media and mastoiditis. Brain computed tomography scan detected right sigmoid and transverse sinus thrombosis, as well as a subperiosteal abscess. Fusobacterium necrophorum and Haemophilus Influentiae were detected on cultural sampling. A multidisciplinary approach along with a combination of medical and surgical therapy allowed the patient's full recovery. CONCLUSION: Cerebral venous sinus thrombosis is a rare but severe complication of acute otitis media and mastoiditis. The management of this pathological condition is always challenging and an interdisciplinary approach is frequently required. Current therapeutic options include a combination of medical and surgical therapy. A patient-centered approach should guide timing and treatment management.

Olfactory Malformations in Mendelian Disorders of the Epigenetic Machinery.

Usually overlooked by physicians, olfactory abnormalities are not uncommon. Olfactory malformations have recently been reported in an emerging group of genetic disorders called Mendelian Disorders of the Epigenetic Machinery (MDEM). This study aims to determine the prevalence of olfactory malformations in a heterogeneous group of subjects with MDEM. We reviewed the clinical data of 35 patients, 20 females and 15 males, with a mean age of 9.52 years (SD 4.99). All patients had a MDEM and an already available high-resolution brain MRI scan. Two experienced neuroradiologists reviewed the MR images, noting abnormalities and classifying olfactory malformations. Main findings included Corpus Callosum, Cerebellar vermis, and olfactory defects. The latter were found in 11/35 cases (31.4%), of which 7/11 had Rubinstein-Taybi syndrome (RSTS), 2/11 had CHARGE syndrome, 1/11 had Kleefstra syndrome (KLFS), and 1/11 had Weaver syndrome (WVS). The irregularities mainly concerned the olfactory bulbs and were bilateral in 9/11 patients. With over 30% of our sample having an olfactory malformation, this study reveals a possible new diagnostic marker for MDEM and links the epigenetic machinery to the development of the olfactory bulbs.