Development of a Heart Failure Palliative Care Educational Program for Nurses: A Multi-Method Approach.

Background: Comprehensive palliative care for patients with heart failure can be developed by educating cardiac nurses. The current study aimed to design a heart failure palliative care educational program for nurses. Materials and Methods: This study was carried out using the multi-method approach based on two out of four steps of Uys educational program development at Dr. Chamran Hospital, Isfahan, in 2020-2021. In step 1, educational needs were collected through literature review, interviews with 15 patients and 10 nurses, examination of patients' documents and medical records, and observation. Then, in step 2, the importance and necessity of teaching the proposed topics and the teaching and evaluation method of the items were assessed through two rounds of delphi technique (15 expert panel members). Eventually, the educational program was finalized. Results: In step 1, the educational needs of nurses were identified in 6 general fields and 26 general learning topics. In step 2, educational needs [specialized knowledge (55% necessity and 55% importance) and social support (33% necessity and 33% importance)], teaching methods (role-playing, experiential learning, and journal club), and evaluation method (the information analysis method) were removed due to a lack of consensus (11%). Finally, the main parts of the program, including the program mission and vision, general learning topics, general goals, objectives, teaching strategies, and evaluation strategies, were compiled. Conclusions: This program provides nurses with up-to-date information on various aspects of the physical, psychological, social, spiritual, and educational needs of heart failure patients and ensures the provision of better services to them.

The diagnostic value of MRI findings in pediatric idiopathic intracranial hypertension: a case-control study.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a rare medical condition in children. Based on the different radiological findings reported in various studies in pediatric IIH, this study was conducted to determine the diagnostic value of MRI findings in diagnosing IIH in children. METHODS: In this retrospective study, the medical records of all children aged 1 to 18 years who visited Ghaem Hospital in Mashhad, Iran, between 2012 and 2022 and were diagnosed with IIH were gathered. Forty-nine cases of children with IIH and 48 control cases of children with the first unprovoked seizure with no indications of increased intracranial pressure for comparison were selected. Patient demographic information and MRI findings were extracted. The comparison between different MRI findings in the case and control groups was conducted using statistical tests. RESULTS: In the case group, the mean diameter of the subarachnoid space expansion around the optic nerve was 5.96 ± 1.21, compared to 4.79 ± 0.33 in the control group, with statistically significant difference (P < 0.001). All the patients with flattening of the posterior globe or transverse sinus stenosis were in the case group, and the frequency of these findings in the case group was significantly higher than in the control group (P < 0.001). The majority of patients (95.5%) classified under category 3 and 4 of empty sella were part of the case group, and the statistical test results indicated a significant difference between the two groups (P < 0.001). The optic nerve sheath diameter cut-off of 5.35 mm, when used for expansion of the subarachnoid space around the optic nerve, with a sensitivity of 82% and a specificity of 100% in diagnosing IIH. CONCLUSION: The most reliable diagnostic indicators for diagnosing IIH in children are perioptic subarachnoid space expansion with high sensitivity, and posterior globe flattening and transverse sinus stenosis with high specificity.

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders.

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50 years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as well as hypertrophy of the clava (24%) were common neuroimaging findings. Acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localization and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-myristoylation was similarly affected in acbd6-deficient zebrafish and X. tropicalis models, including Fus, Marcks and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders.

Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder.

PURPOSE: SLC4A10 encodes a plasma membrane-bound transporter, which mediates Na+-dependent HCO3- import, thus mediating net acid extrusion. Slc4a10 knockout mice show collapsed brain ventricles, an increased seizure threshold, mild behavioral abnormalities, impaired vision, and deafness. METHODS: Utilizing exome/genome sequencing in families with undiagnosed neurodevelopmental disorders and international data sharing, 11 patients from 6 independent families with biallelic variants in SLC4A10 were identified. Clinico-radiological and dysmorphology assessments were conducted. A minigene assay, localization studies, intracellular pH recordings, and protein modeling were performed to study the possible functional consequences of the variant alleles. RESULTS: The families harbor 8 segregating ultra-rare biallelic SLC4A10 variants (7 missense and 1 splicing). Phenotypically, patients present with global developmental delay/intellectual disability and central hypotonia, accompanied by variable speech delay, microcephaly, cerebellar ataxia, facial dysmorphism, and infrequently, epilepsy. Neuroimaging features range from some non-specific to distinct neuroradiological findings, including slit ventricles and a peculiar form of bilateral curvilinear nodular heterotopia. In silico analyses showed 6 of 7 missense variants affect evolutionarily conserved residues. Functional analyses supported the pathogenicity of 4 of 7 missense variants. CONCLUSION: We provide evidence that pathogenic biallelic SLC4A10 variants can lead to neurodevelopmental disorders characterized by variable abnormalities of the central nervous system, including altered brain ventricles, thus resembling several features observed in knockout mice.

Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly.

Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. Thirty-one LIS-associated genes have been previously described. Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2. In this report, we describe biallelic truncating variants in CASP2, another subunit of PIDDosome complex. Seven patients from five independent families presenting with a neurodevelopmental phenotype were identified through GeneMatcher-facilitated international collaborations. Exome sequencing analysis was carried out and revealed two distinct novel homozygous (NM_032982.4:c.1156delT (p.Tyr386ThrfsTer25), and c.1174 C > T (p.Gln392Ter)) and compound heterozygous variants (c.[130 C > T];[876 + 1 G > T] p.[Arg44Ter];[?]) in CASP2 segregating within the families in a manner compatible with an autosomal recessive pattern. RNA studies of the c.876 + 1 G > T variant indicated usage of two cryptic splice donor sites, each introducing a premature stop codon. All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings. Other findings included developmental delay, attention deficit hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. In summary, we present patients with CASP2-related ID, anterior-predominant LIS, and pachygyria similar to previously reported patients with CRADD and PIDD1-related disorders, expanding the genetic spectrum of LIS and lending support that each component of the PIDDosome complex is critical for normal development of the human cerebral cortex and brain function.

Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity.

BACKGROUND: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship. METHODS: Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl, ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during development. Functional complementation with patient variant transcripts was conducted to systematically assess protein functionality as a readout for pathogenicity. RESULTS: A cohort of 14 individuals from 12 unrelated families exhibited highly variable clinical phenotypes, with the majority of them presenting at least one additional variant, potentially accounting for a blended phenotype and complicating phenotypic understanding. We also uncovered extreme clinical heterogeneity and high allele frequencies, occasionally incompatible with a fully penetrant recessive disorder. Human cDNA of previously described and new variants were tested in an ogdhl zebrafish knockout model, adding functional evidence for variant reclassification. We disclosed evidence of hypomorphic alleles as well as a loss-of-function variant without deleterious effects in zebrafish variant testing also showing discordant familial segregation, challenging the relationship of OGDHL as a conventional Mendelian gene. Going further, we uncovered evidence for a complex compensatory relationship among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental disorders and exhibit complex transcriptional compensation patterns with partial functional redundancy. CONCLUSIONS: Based on the results of genetic, clinical, and functional studies, we formed three hypotheses in which to frame observations: biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all. Our study further highlights the continuing challenges of assessing the validity of reported disease-gene associations and effects of variants identified in these genes. This is particularly more complicated in making genetic diagnoses based on identification of variants in genes presenting a highly heterogenous phenotype such as "OGDHL-related disorders".

Development, implementation, and evaluation of a program to expand the nurse's roles in colorectal cancer prevention: A mixed-methods protocol study.

BACKGROUND: Nurses play an important role in cancer prevention. However, studies conducted on nurses' roles, in the field of cancer prevention in Iran, are very limited. This study will identify the role of nurses and designs, implements, and evaluates a program to expand their role in the prevention of colorectal cancer (CRC). MATERIALS AND METHODS: This exploratory mixed-methods study will be performed using quantitative-qualitative methods in three consecutive stages. In the first phase, a qualitative study will be conducted to identify the potential and actual roles of nurses in Iran using in-depth semi-structured interviews. Participants will be selected by purposive and snowball sampling, followed by a literature review; the actual and potential roles of nurses at the primary, secondary, and tertiary levels of CRC prevention in Iran and around the world will be extracted. And the actual role is determined. In the second phase, the roles of nurses will be prioritized using the modified Delphi method, and the program will be designed. In the third phase, the part of the program will be implemented as a quasi-experimental intervention, and the effect of the intervention will be evaluated. CONCLUSION: Developing a program can provide some evidence for promoting nurses' position in cancer prevention. Moreover, it is expected that this program promotes knowledge and empowerment and the position of nurses to provide primary, secondary, and tertiary cancer prevention. The entry of nurses into the field of cancer prevention leads to better quality care and more cost-effectiveness.

The first reports of FA2H-associated neurodegeneration from two unrelated Iranian families.

BACKGROUND: NBIA (neurodegeneration with brain iron accumulation) is a diverse collection of neurodegenerative illnesses defined by iron accumulation in the basal ganglia. The fatty acid hydroxylase-associated neurodegeneration, or FAHN, is one of the uncommon subtypes of NBIAs, associated with inherited autosomal recessive mutations in gene coding the membrane-bound fatty acid 2 hydroxylase (FA2H) enzyme. CASES: Here, we report two cases with FAHN from two unrelated families from Iran confirmed by whole exome sequencing. CONCLUSION: FAHN is an uncommon variant of NBIA that may manifest as spastic paraparesis without signs of iron buildup on brain imaging. As a result, it should be taken into account while making a differential diagnosis of the hereditary spastic paraplegia (HSP) syndrome, especially in individuals who lack iron deposits.

One-Step Preparation of Luteolin Nanoemulsion and Evaluation of its Anti-inflammatory Effect in Animal Models.

BACKGROUND: Nanoemulsions are promising drug delivery systems for topical application owing to the high transdermal penetration. OBJECTIVE: Due to the side effects of existing anti-inflammatory drugs, much attention has been paid to natural products such as flavonoids. The aim of this work was to formulate luteolin nanoemulsion (LNE) and to evaluate its anti-inflammatory effect. METHODS: LNE was prepared using the low-energy spontaneous emulsion method and characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and dynamic light scattering (DLS). The anti-inflammatory effect of LNE was assessed in formalin and acetic acid-induced inflammation methods (Whittle test). Treatment with LNE (i.p, 4 consecutive days, 40 mg/kg) was compared with diclofenac 25 mg/kg and normal saline. In the formalin test, data were recorded at 1, 2 and 4 hours after formalin injection and in the Wittle test, the extent of Evans blue leakage in the peritoneal cavity was considered as vascular permeability. RESULTS: Formalin-induced edema decreased in the LNE group, but this reduction was not significant (p > 0.05), however, in Whittle test, both LNE and diclofenac significantly reduced Evans blue leakage compared with the group treated with acetic acid alone (p < 0.05). CONCLUSION: Our results confirm the anti-inflammatory effect of LNE and give up a new platform for the design and development of bio-based carriers for more successful drug delivery.

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated with torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with AMC5-TOR1A have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with foetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71%, with higher mortality in males. Death occurred at a median age of 1.2 months (1 week-9 years), due to respiratory failure, cardiac arrest or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival.

Therapeutical impacts of transcranial direct current stimulation on drug-resistant epilepsy in pediatric patients: A double-blind parallel-group randomized clinical trial.

BACKGROUND: Drug-resistant epilepsy is a challenging problem in pediatrics. Transcranial direct current stimulation (TDCS) is a non-invasive neurostimulation technique suggested as a promising method for treating epilepsy. This study aims to evaluate the efficacy of TDCS in focal epilepsy in children with drug-resistant epilepsy. METHOD: We conducted a randomized sham-controlled study with 18 subjects between 6 and 16 years of age, divided equally into two groups. TDCS was performed in 20-minute daily stimulation protocol for five days for both groups. The current intensity was one mA for the first three days, increasing to 1.5 mA on day four and 2 mA on the last day of stimulation. EEG was done before and after the intervention. RESULTS: There was a significant reduction in seizure duration in the case group compared with the sham group. CONCLUSION: five consecutive days of performing TDCS significantly reduced seizure duration in children with focal Drug-resistant epilepsy. However,further studies in this field are necessary to test the effectiveness and set up a coherent and comprehensive protocol.

Grief and bereavement of family and friends around medical assistance in dying: scoping review.

OBJECTIVES: The increase in the number of jurisdictions legalising medical assistance in dying (MAiD) has contributed to a growth in the number of family and friends who may face unique elements of grief and bereavement. The aim of this study was to review the literature of grief and bereavement of family and friends following MAiD, and to summarise findings for the development of community resources and programming. METHODS: We performed a scoping review with workshop consultation of stakeholders. Six electronic databases and the grey literature were searched for qualitative, quantitative and review articles. Content-analytical techniques and multidisciplinary discussions led to the development of concepts and a conceptual framework. RESULTS: Twenty-eight articles met the inclusion criteria. We identified five concepts that impact the grief and bereavement of family/friends: relationships between family/friends and the patient as well as healthcare providers; aspects of MAiD grief which can include secrecy and/or anticipatory grief; preparations which may include family/friends and should be centralised and harmonised; end of life as an opportunity for ceremony; and the aftereffects during which mental health outcomes are studied. CONCLUSION: This multidisciplinary scoping review incorporates stakeholder consultation to find that support is needed to address the complicated and changing emotions of family/friends before, during and after a MAiD death. Furthermore, additional societal normalisation of MAiD is necessary to reduce secrecy and stigma and improve the accessibility of resources for family/friends.

Parietal bone osteoid osteoma: A rare cause of button sequestrum sign in pediatrics. Case report and review of literature.

The current study evaluates a rare case of parietal bone osteoid osteoma in pediatrics and review the differential diagnosis of button sequestrum sign in the literature. A 12-year-old girl expressed localized pain in the right parietal bone. MRI represented enhancing nodule with button sequestrum sign appearance.

Nurse's Roles in Colorectal Cancer Prevention: A Narrative Review.

The objective of this paper is to investigate the different roles of nurses as members of healthcare teams at the primary, secondary, and tertiary levels of colorectal cancer prevention. The research team conducted a narrative review of studies involving the role of nurses at different levels of colorectal cancer prevention, which included a variety of quantitative, qualitative, and mixed-method studies. We searched PubMed, Scopus, Web of Science, Cochrane Reviews, Magiran, the Scientific Information Database (SID), Noormags, and the Islamic Science Citation (ISC) databases from ab initio until 2021. A total of 117 studies were reviewed. Nurses' roles were classified into three levels of prevention. At the primary level, the most important role related to educating people to prevent cancer and reduce risk factors. At the secondary level, the roles consisted of genetic counseling, stool testing, sigmoidoscopy and colonoscopy, biopsy and screening test follow-ups, and chemotherapy intervention, while at the tertiary level, their roles were made up of pre-and post-operative care to prevent further complications, rehabilitation, and palliative care. Nurses at various levels of prevention care also act as educators, coordinators, performers of screening tests, follow-up, and provision of palliative and end-of-life care. If these roles are not fulfilled at some levels of colorectal cancer, it is generally due to the lack of knowledge and competence of nurses or the lack of instruction and legal support for them. Nurses need sufficient clinical knowledge and experience to perform these roles at all levels.

PI4K2A deficiency causes innate error in intracellular trafficking with developmental and epileptic-dyskinetic encephalopathy.

OBJECTIVE: Intracellular signaling networks rely on proper membrane organization to control an array of cellular processes such as metabolism, proliferation, apoptosis, and macroautophagy in eukaryotic cells and organisms. Phosphatidylinositol 4-phosphate (PI4P) emerged as an essential regulatory lipid within organelle membranes that defines their lipid composition and signaling properties. PI4P is generated by four distinct phosphatidylinositol 4-kinases (PI4K) in mammalian cells: PI4KA, PI4KB, PI4K2A, PI4K2B. Animal models and human genetic studies suggest vital roles of PI4K enzymes in development and function of various organs, including the nervous system. Bi-allelic variants in PI4KA were recently associated with neurodevelopmental disorders (NDD), brain malformations, leukodystrophy, primary immunodeficiency, and inflammatory bowel disease. Here, we describe patients from two unrelated consanguineous families with PI4K2A deficiency and functionally explored the pathogenic mechanism. METHODS: Two patients with PI4K2A deficiency were identified by exome sequencing, presenting with developmental and epileptic-dyskinetic encephalopathy. Neuroimaging showed corpus callosum dysgenesis, diffuse white matter volume loss, and hypoplastic vermis. In addition to NDD, we observed recurrent infections and death at toddler age. We further explored identified variants with cellular assays. RESULTS: This clinical presentation overlaps with what was previously reported in two affected siblings with homozygous nonsense PI4K2A variant. Cellular studies analyzing these human variants confirmed their deleterious effect on PI4K2A activity and, together with the central role of PI4K2A in Rab7-associated vesicular trafficking, establish a link between late endosome-lysosome defects and NDD. INTERPRETATION: Our study establishes the genotype-phenotype spectrum of PI4K-associated NDD and highlights several commonalities with other innate errors of intracellular trafficking.

Recurrent Painful Ophthalmoplegic Neuropathy with Unilateral Oculomotor and Trochlear Nerve Palsy in an 8-year-old Girl.

BACKGROUND: Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder with a unilateral headache accompanied by ipsilateral episodes of painful ocular cranial nerve neuropathy, which typically occurs in childhood. CASE REPORT: We report an 8-year-old female with four episodes of RPON involving unilateral third and fourth cranial nerves. Right eye exotropia and complete ptosis were detected on examination. Brain MRI images revealed right third nerve enhancement where it exits from the brainstem. She completely recovered after 5 weeks with the administration of prednisolone and indomethacin. DISCUSSION AND CONCLUSION: Due to the rarity of this condition in children, recurrent painful ophthalmoplegic neuropathy should be considered as a differential diagnosis of unilateral or bilateral painful ophthalmoplegia, particularly with a history of migrainous headache. Since it is a treatable entity, and repeated attacks may lead to permanent sequela, early intervention is crucial.

A case report of Posterior reversible encephalopathy syndrome with spinal cord involvement (PRES-SCI) as an atypical presentation of PRES in children: A case report and review of the literature.

Posterior reversible encephalopathy syndrome (PRES) has a broad spectrum of clinical presentations and radiological features. Diagnosis of PRES is established based on reversible clinical manifestations and sequential neuroimaging findings. Atypical MRI features include hemorrhage, restricted diffusion or contrast enhancement of lesions, and involvement of the temporal and frontal lobes, brainstem, basal ganglia, corpus callosum, cerebellum, and spine. Atypical PRES, with or without spinal cord involvement, is a rare presentation, especially in children. Until 2020, only five cases of PRES with spinal cord involvement (PRES-SCI) were reported in the pediatric population. Case Report: Here, we present the youngest diagnosed case of PRES-SCI so far. According to the literature, all six cases of PRES-SCI showed high signal intensities on T2-weighted images of the brainstem and cervical cord, which had completely resolved in the follow-up MRI of the brain and spinal cord. All six patients had hypertension due to renal disease, except one girl with chemotherapy-induced hypertension. Headache, altered mental status, seizure, and visual impairment were the most common symptoms, respectively. Facial palsy was a remarkable warning sign in some patients before hospitalization.Although PRES-SCI is rare in children, since it is a reversible condition, prompt diagnosis and management can positively affect its prognosis.

Identification of three novel homozygous variants in COL9A3 causing autosomal recessive Stickler syndrome.

BACKGROUND: Stickler syndrome (STL) is a rare, clinically and molecularly heterogeneous connective tissue disorder. Pathogenic variants occurring in a variety of genes cause STL, mainly inherited in an autosomal dominant fashion. Autosomal recessive STL is ultra-rare with only four families with biallelic COL9A3 variants reported to date. RESULTS: Here, we report three unrelated families clinically diagnosed with STL carrying different novel biallelic loss of function variants in COL9A3. Further, we have collected COL9A3 genotype-phenotype associations from the literature. CONCLUSION: Our report substantially expands the molecular genetics and clinical basis of autosomal recessive STL and provides an overview about allelic COL9A3 disorders.