A Novel Skin Incision for Posterior Fossa Midline and Paramedian Lesions: A Technical Note and Case Series.

Approaching posterior fossa pathologies is fairly challenging. Poor exposure, cerebrospinal fluid (CSF) leak following surgery, post-operative suboccipital and neck pain, as well as wound healing are all common complications following traditional suboccipital midline incision. Herein, we present a novel incision for approaching posterior fossa pathologies. The incision is shaped like a question mark and makes a musculofascial flap supplied by the occipital artery on top as well as a wide area for craniotomy. In our technique, the dura is also incised in a question mark-shaped manner. The new incision was used to operate on three patients who had masses in the posterior fossa. Following surgeries, none of the patients experienced any adverse events such as CSF leak, wound complications, severe suboccipital pain, and neck instability. This new incision not only facilitates approaching pathologies in the posterior fossa by providing wider exposure but also enables us to perform watertight dural closure, which reduces CSF leak. Furthermore, as the muscular incision provides a sufficient area for craniotomy, muscular retraction can be minimized to reduce post-operative pain. Moreover, unlike the midline avascular incision, the flap is well supplied by the occipital artery, which facilitates the healing procedure.

Elevated skull fractures: an institutional experience and individual participant data meta-analysis.

Elevated skull fracture (ESF) is a rare but potentially life-threatening type of skull fracture. The literature on this topic is relatively sparse. Herein, we conducted a meta-analysis of all the patients reported in the literature with ESFs with respect to their clinical management to better inform practice. On 20th of January 2023, we conducted a systematic search of literature to find all published cases of ESF. We also conducted a retrospective review of ESF cases from our institution. The data collection and analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After screening, 28 studies met the inclusion criteria. A total of 104 individual patients were included in the meta-analysis, with a median age of 24 years and 85.7% of whom were males. 11 patients (11.2%) had an unfavorable outcome while 37 (35.2%) had one or more complications. We found that GCS on admission is an independent predictor of poor outcome in ESF (odds ratio (95% confidence interval) = 1.605 (1.110-2.315), p value = 0.012). Regarding complications, dural injury (odds ratio (95% confidence interval) = 66.667 (7.407-500.00), p value < 0.001) and multiple bone involvement (odds ratio (95% confidence interval) = 6.849 (2.127-22.222), p value = 0.001) were independent predictors of complication. ESFs represent a rare yet consequential form of cranial injury, carrying potentially life-threatening implications if not promptly addressed. In this study, we present the meta-analysis of outcomes and complications within this patient cohort, offering a comprehensive synthesis of existing literature on this pathology. However, further investigation is imperative to provide higher-quality evidence and address lingering uncertainties in the classification and management of ESFs.

Precision and Speed at Your Fingertips: An Automated Intracranial Hematoma Volume Calculation.

BACKGROUND: Intracranial hemorrhage (ICH) is a severe condition that requires rapid diagnosis and treatment. Automated methods for calculating ICH volumes can reduce human error and improve clinical decisioPlease provide professional degrees (e.g., PhD, MD) for the corresponding author.n-making. A novel automated method has been developed that is comparable to the ABC/2 method in terms of speed and accuracy while providing more accurate volumetric data. METHODS: We developed a novel automated algorithm for calculating intracranial blood volume from computed tomography (CT) scans. The algorithm consists of a Python script that processes Digital Imaging and Communications in Medicine images and determines the blood volume and ratio. The algorithm was validated against manual calculations performed by neurosurgeons. RESULTS: Our novel automated algorithm for calculating intracranial blood volume from CT scans demonstrated excellent agreement with the ABC/2 method, with a median overall difference of just 1.46 mL. The algorithm was also validated in patient groups with ICH, epidural hematoma (EDH), and SDH, with agreement coefficients of 0.992, 0.983, and 0.997, respectively. CONCLUSIONS: The study introduces a novel automated algorithm for calculating the volumes of various ICHs (EDH, and SDH) within CT scans. The algorithm showed excellent agreement with manual calculations and outperformed the commonly used ABC/2 method, which tends to overestimate ICH volume. The automated algorithm offers a more accurate, efficient, and time-saving approach to quantifying ICH, EDH, and SDH volumes, making it a valuable tool for clinical evaluation and decision-making.

2- to 20-year myelomeningocele follow-up outcomes from a referral center in Southern Iran: the Shiraz experience.

BACKGROUND: The current convention for treatment of children with myelomeningocele (MMC) is timely surgical intervention combined with long-term follow-up by a multidisciplinary specialized team. This study aims to investigate the outcomes of MMC patients treated at Namazi Hospital. METHODS: All children presenting to Namazi Hospital with myelomeningocele between May 2001 and August 2020 were eligible for this study. For those with a documented telephone number, follow-up phone surveys with the patient's caregivers, on top of the review of the medical documents were carried out to assess mortality, morbidities, and the functional outcome of the care provided to them. RESULTS: A total of 125 patients were studied (62 females). All of the patients were followed up for a mean duration of 6.28 years (range 1-23 years). The majority were located in the lumbosacral area. All of the patients underwent postnatal surgical intervention for MMC in Namazi Hospital. Mean age at surgery was 9.51 days. There were statistically significant differences between urinary and bowel incontinence and presence of scoliosis, MMT grading of the lower limbs, school attendance, number of readmissions, and requirement of laminectomy at the initial surgical intervention. CONCLUSIONS: This study is the first to characterize the long-term outcomes of MMC patients in Iran. This study illustrates that there is a great need for improved access to and coordination of care in antenatal, perioperative, and long-term stages to improve morbidity and mortality.

Surgical outcomes of myelomeningocele repair: A 20-year experience from a single center in a middle-income country.

BACKGROUND AND PURPOSE: Spina bifida is the second major cause of congenital disorders and the most common central nervous system congenital malformation compatible with life primarily. Herein, we describe the short-term outcome of post-natal Myelomeningocele (MMC) surgical management and predictors of its postoperative complications and mortality. METHODS: This retrospective chart review studies the children who underwent post-natal surgical management for MMC in Namazi hospital, a tertiary referral center, in southern Iran from May 2001 to September 2020. RESULTS: 248 patients were included in this study. The mean age at the operation was 8.47 ± 8.69 days. The most common site of involvement of MMC was Lumbosacral (86%, n = 204). At the evaluation conducted prior to the operation, cerebrospinal fluid leak was observed in 7% (n=16) of the patients. Postoperatively, 5.7% of the patients expired in the 30-day follow-up after the operation (n = 14), while 24% needed readmission (n = 47). The most common complications leading to readmission were wound dehiscence (n = 10, 42%) and wound purulence (n = 6, 25%). Only the site of the lesion (p-value = 0.035) was associated with postoperative complication. After controlling for potential confounders, the site of the lesion (adjusted odds ratio = 0.146, 95% confidence interval = 0.035-0.610, p-value = 0.008) and age at surgery (adjusted odds ratio = 1.048, 95% confidence interval = 1.002-1.096, p-value = 0.041) were significantly associated with mortality CONCLUSIONS: The age of the patients at the surgery and the site of the lesion are the two factors that were associated with mortality. However, further investigations into preoperative interventions and risk factors to mitigate the risk of complications and mortality are highly encouraged.

Effect of low fibrinogen level on in-hospital mortality and 6-month functional outcome of TBI patients, a single center experience.

In patients affected by traumatic brain injury (TBI), hypofibrinogenemia within the initial hours of trauma can be expected due to vascular and inflammatory changes. In this study, we aimed to evaluate the effect of hypofibrinogenemia on the in-hospital mortality and 6-month functional outcomes of TBI patients, admitted to Rajaee Hospital, a referral trauma center in Shiraz, Iran. This study included all TBI patients admitted to our center who had no prior history of coagulopathy or any systemic disease, were alive on arrival, and had not received any blood product before admission. On admission, hospitalization, imaging, and 6-month follow-up information of included patients were extracted from the TBI registry database. The baseline characteristics of patients with fibrinogen levels of less than 150 mg/dL were compared with the cases with higher levels. To assess the effect of low fibrinogen levels on in-hospital mortality, a uni- and multivariate was conducted between those who died in hospital and survivors. Based on the 6-month GOSE score of patients, those with GOSE < 4 (unfavorable outcome) were compared with those with a favorable outcome. A total of 3049 patients (84.3% male, 15.7% female), with a mean age of 39.25 ± 18.87, met the eligibility criteria of this study. 494 patients had fibrinogen levels < 150 mg/dl, who were mostly younger and had lower average GCS scores in comparison to cases with higher fibrinogen levels. By comparison of the patients who died during hospitalization and survivors, it was shown that fibrinogen < 150 mg/dl is among the prognostic factors for in-hospital mortality (OR:1.75, CI: 1.32:2.34, P-value < 0.001), while the comparison between patients with the favorable and unfavorable functional outcome at 6-month follow-up, was not in favor of prognostic effect of low fibrinogen level (OR: 0.80, CI: 0.58: 1.11, P-value: 0.19). Hypofibrinogenemia is associated with in-hospital mortality of TBI patients, along with known factors such as higher age and lower initial GCS score. However, it is not among the prognostic factors of midterm functional outcome.

Development of a Novel Neurological Score Combining GCS and FOUR Scales for Assessment of Neurosurgical Patients with Traumatic Brain Injury: GCS-FOUR Scale.

BACKGROUND: Consciousness assessment is crucial for patients with traumatic brain injury. In this study, we developed a novel scoring system combining the Glasgow coma scale (GCS) and the full outline of unresponsiveness (FOUR) and evaluated its association with the intensive care unit (ICU) length of stay, mortality, and functional outcome. METHODS: We retrospectively analyzed the data from patients with traumatic brain injury admitted to the neurosurgical ICU of our institution during a 2-year period. The eye and motor components of the GCS and the brainstem reflex component of the FOUR were used to compute the GCS-FOUR. We performed statistical analysis to demonstrate the association between the GCS, FOUR, and GCS-FOUR and the ICU length of stay, mortality, the development of a persistent vegetative state, and desirable recovery. RESULTS: A total of 140 patients were included. The mean age was 30.6 years, and 89.3% were male. All 3 scores were associated with the ICU length of stay, mortality, a persistent vegetative state, and good recovery. In terms of predicting mortality, the GCS score exhibited a slight superiority compared with the other indexes, and the GCS-FOUR score showed a slight superiority over the other indexes in predicting for good recovery. CONCLUSIONS: The GCS-FOUR is a novel scoring system comparable to the GCS and FOUR regarding its association with functional status after injury, ICU length of stay, and mortality. The GCS-FOUR score provides greater neurological detail than the GCS due to the inclusion of brainstem reflexes, in addition to using the experience of healthcare providers with the GCS score compared with the FOUR in most settings.

Outcomes of the early endoscopic-assisted suturectomy for treatment of multisuture craniosynostosis.

To present the outcomes and adverse events associated with the endoscopic-assisted, minimally invasive suturectomy in patients with multisuture synostosis. This retrospective cohort study included children < 65 days of age who underwent endoscopic-assisted suturectomy (EAS) for multisuture craniosynostosis at a single tertiary referral center from 2013 to 2021. The primary outcome was calvarial expansion, and the secondary outcome was adverse events. The pre- and post-operative 3-dimensional brain computed tomography (CT) scan was used to calculate the intracranial volume and cephalic index. During a period of 2 years, 10 infants (10-64 days) diagnosed with multisuture synostosis underwent single-stage EAS of every affected suture in our center. The coronal suture was the most prevalent involved suture among our cases. The mean age and weight of the patients were 39 ± 17.5 days and 4.39 ± 0.8 kg, respectively. The surgical procedure took 42 ± 17.4 min of time and caused 46 ± 25.4 mL of bleeding on average. Ninety percent of the operations were considered successful (n = 9) regarding calvarial expansion. There were two complications, one requiring an open vault surgery and one repairing a leptomeningeal cyst. In the eight patients who did not necessitate further interventions, the mean pre-operative intracranial volume was 643.3 ± 189.4 cm3. The follow-up results within the average of 38.9 months after surgery showed that as age increases, the intracranial volume also increased significantly (R: 0.6, P < 0.0001), which suggests continued skull growth in patients who underwent EAS. With the low rate of intra- or post-operative complications and promising results on revising the restricted skull sutures, EAS seems both a safe and effective therapeutic modality in patients with multisuture synostosis, especially if completed in the first months after birth.

Intronic OTOF mutation causes an atypical splicing defect resulting in auditory neuropathy spectrum disorder.

Pathogenic variants in OTOF cause auditory neuropathy spectrum disorder (ANSD), namely prelingual nonsyndromic ANSD and temperature-sensitive ANSD (TS-ANSD). All study subjects provided blood sample for genetic analysis and sequencing. Wholeexome sequencing was carried out to identify the causative pathogenic variant. RNAwas extracted to analyse the messenger RNA (mRNA) resulting from the transcription of OTOF. Here, we identified a family with OTOF-related ANSD. This disorder was caused by an intronic mutation in OTOF (NM_194248: c.2406>4A[G). In further analysis, we proved that this variant causes a splicing defect resulting in the omission of exon 20 from the mRNA transcribed from OTOF. In this study, we demonstrated that the variant is four nucleotides away from the conventional splicing site, and our findings suggest that splicing mechanisms need to be better understood, as well as how neighbouring regions may impact splicing.

A novel scoring system for early assessment of the risk of the COVID-19-associated mortality in hospitalized patients: COVID-19 BURDEN.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) presentations range from those similar to the common flu to severe pneumonia resulting in hospitalization with significant morbidity and/or mortality. In this study, we made an attempt to develop a predictive scoring model to improve the early detection of high risk COVID-19 patients by analyzing the clinical features and laboratory data available on admission. METHODS: We retrospectively included 480 consecutive adult patients, aged 21-95, who were admitted to Faghihi Teaching Hospital. Clinical and laboratory features were collected from the medical records and analyzed using multiple logistic regression analysis. The final data analysis was utilized to develop a simple scoring model for the early prediction of mortality in COVID-19 patients. The score given to each associated factor was based on the coefficients of the regression analyses. RESULTS: A novel mortality risk score (COVID-19 BURDEN) was derived, incorporating risk factors identified in this cohort. CRP (> 73.1 mg/L), O2 saturation variation (greater than 90%, 84-90%, and less than 84%), increased PT (> 16.2 s), diastolic blood pressure (≤ 75 mmHg), BUN (> 23 mg/dL), and raised LDH (> 731 U/L) were the features constituting the scoring system. The patients are triaged to the groups of low- (score < 4) and high-risk (score ≥ 4) groups. The area under the curve, sensitivity, and specificity for predicting mortality in patients with a score of ≥ 4 were 0.831, 78.12%, and 70.95%, respectively. CONCLUSIONS: Using this scoring system in COVID-19 patients, the patients with a higher risk of mortality can be identified which will help to reduce hospital care costs and improve its quality and outcome.

Analysis of DYRK1B, PPARG, and CEBPB Expression Patterns in Adipose-Derived Stem Cells from Patients Carrying DYRK1B R102C and Healthy Individuals During Adipogenesis.

Background: Metabolic syndrome (MetS) is a group of signs and symptoms that are associated with a higher risk of type 2 diabetes mellitus and cardiovascular diseases. The major risk factor for developing MetS is abdominal obesity, which is caused by an increase in adipocyte size or quantity. Increased adipocyte quantity is a result of differentiation of stem cells into adipose tissue. Numerous studies have investigated the expression of key transcription factors, including PPARG and CEBPB during adipocyte differentiation in murine cells such as 3T3-L1 cell lines. To better understand the expression changes during the process of fat accumulation in adipose-derived stem cells (ASCs), we compared the expression of DYRK1B, PPARG, and ẟB in ASCs between the patient (harboring DYRK1B R102C) and control (healthy individuals) groups. Methods: Gene expression was evaluated on the eighth day before induction and days 1, 5, and 15 postinduction. The pluripotent capacity of ASCs and the potential for differentiation into adipocytes were confirmed by flow cytometry analysis of surface markers (CD34, CD44, CD105, and CD90), and Oil Red O staining, respectively. The Expression of DYRK1B, PPARG, and CEBPB were assessed by real-time-polymerase chain reaction in patients and normal individuals. The effects of AZ191, a potent small molecule inhibitor on DYRK1B and CEBPB expression in patients' samples were studied. Result: The expression of DYRK1B kinase and transcription factors (CEBPB and PPARG) are higher in ASCs harboring DYRK1B R102C compared with noncarriers on days 5 and 15 during adipocyte differentiation. These proteins may be helpful to elucidate the mechanisms underlying obesity and obesity-related disorders like MetS. Furthermore, the new compound AZ191 exhibited inhibitory activity toward DYRK1B and CEBPB. We suggest that AZ191 may be helpful in defining the potential roles of DYRK1B and CEBPB in adipogenesis.

The Evolving Role of Next-Generation Sequencing in Pediatric Neurosurgery: A Call for Action for Research, Clinical Practice, and Optimization of Care.

Next-generation sequencing (NGS) is one of the most promising technologies that have truly revolutionized many aspects of clinical practice in recent years. It has been and is increasingly applied in many disciplines of medicine; however, it seems that pediatric neurosurgery despite its great potential has not truly embraced this new technology and is hesitant to use it in routine practice and guidelines. In this review, we summarize the developments that led to the establishment of NGS technology, review the applications and potentials of NGS in the disorders treated by pediatric neurosurgeons, and discuss the steps that we need to be taken to better harness NGS in pediatric neurosurgery.

A combination of two novels homozygous FCSK variants cause disorder of glycosylation with defective fucosylation: New patient and literature review.

Pathogenic variants in FCSK cause Congenital Disorder of Glycosylation with Defective Fucosylation-2 (FCSK-CDG; MIM: 618,324). It is a rare autosomal recessive genetic disease caused by defects in the L-fucose kinase, which is necessary for the fucose salvage pathway. Herein, we report two novel variants in an Iranian patient, the fourth individual with FCSK-CDG described in the literature. Two homozygous variants in FCSK (rs376941268; NM_145059.3: c.379C > A, p. Leu127Met and rs543223292; NM_145059.3: c.394G > C, p. Asp132His) were identified in the proband. Sanger sequencing conducted on his unaffected parents revealed that they were heterozygous for the same variants. The proband, a four-and-a-half year old Iranian male born to consanguineous parents, manifested Intellectual disability, growth delay, ophthalmic abnormalities, seizures, speech disorder, and feeding difficulties.

MCM2 mutation causes autosomal dominant nonsyndromic hearing loss (DFNA70): novel variant in the second family.

Pathogenic variants in MCM2 could result in mild to severe sensorineural hearing loss in the affected individuals (deafness, autosomal dominant 70; DFNA70; OMIM: 616968), an extremely rare autosomal dominant progressive disorder. Here, we report a novel missense variant (NM_004526:c.388C>T, p.R130C; Clinvar: SCV002072508) in MCM2 in an Iranian family identified by whole-exome sequencing and confirmed by Sanger sequencing. The heterozygous variant (NM_004526:c.388C>T, p.R130C) in MCM2 was identified in the proband and his mother. The proband is a nine-year-old male born to nonconsanguineous parents. The proband was characterized by nonsyndromic hearing loss, while his mother showed a mild form of the disorder. This study reports the second disease-causing variant in MCM2 in the world and confirms that hearing loss arising from variants in MCM2 is nonsyndromic. Nevertheless, as was reported in the previous family, phenotype could vary among the patients with the same variant.

Genotypic and phenotypic spectrum of Myofibrillar Myopathy 7 as a result of Kyphoscoliosis Peptidase deficiency: The first description of a missense mutation in KY and literature review.

KY is located on chromosome 3 and encodes a transglutaminase-like protein in the skeletal muscles, namely Kyphoscoliosis Peptidase. KY is primarily involved in the formation and stabilization of neuromuscular intersections making it essential for the development of the musculoskeletal system. Mutations in KY cause Myofibrillar Myopathy-7 (MFM-7) and Hereditary Spastic Paraplegia (HSP). MFM-7 is an early onset muscle disorder with an autosomal recessive inheritance marked by progressive muscle weakness and joint contractures. Herein, we describe an Iranian family with MFM-7 caused by a homozygous novel variant in KY. We identified a homozygous variant (NM_178554.6:c.1247T > A, p. Ile416Asn) in KY in two patients born to consanguineous parents and the same heterozygous mutation in their parent by Whole-Exome Sequencing. The patients manifest muscle weakness, muscle atrophy, mobility restriction, and hyporeflexia. Lastly, we reviewed the phenotype and corresponding genotype of the previously reported cases with pathogenic variants in KY.

Prediction of 6 months endoscopic third ventriculostomy success rate in patients with hydrocephalus using a multi-layer perceptron network.

OBJECTIVE: Discrimination between patients most likely to benefit from endoscopic third ventriculostomy (ETV) and those at higher risk of failure is challenging. Compared to other standard models, we have tried to develop a prognostic multi-layer perceptron model based on potentially high-impact new variables for predicting the ETV success score (ETVSS). METHODS: Clinical and radiological data of 128 patients have been collected, and ETV outcomes were evaluated. The success of ETV was defined as remission of symptoms and not requiring VPS for six months after surgery. Several clinical and radiological features have been used to construct the model. Then the Binary Gravitational Search algorithm was applied to extract the best set of features. Finally, two models were created based on these features, multi-layer perceptron, and logistic regression. RESULTS: Eight variables have been selected (age, callosal angle, bifrontal angle, bicaudate index, subdural hygroma, temporal horn width, third ventricle width, frontal horn width). The neural network model was constructed upon the selected features. The result was AUC:0.913 and accuracy:0.859. Then the BGSA algorithm removed half of the features, and the remaining (Age, Temporal horn width, Bifrontal angle, Frontal horn width) were applied to construct models. The ANN could reach an accuracy of 0.84, AUC:0.858 and Positive Predictive Value (PPV): 0.92, which was higher than the logistic regression model (accuracy:0.80, AUC: 0.819, PPV: 0.89). CONCLUSION: The research findings have shown that the MLP model is more effective than the classic logistic regression tools in predicting ETV success rate. In this model, two newly added features, the width of the lateral ventricle's temporal horn and the lateral ventricle's frontal horn, yield a relatively high inter-observer reliability.

Recurrent Infections and Immunodeficiency Caused by Severe Pancytopenia Associated with a Novel Life-Threatening Mutation in Hypoxia-Upregulated Protein 1.

HYOU1 encodes a protein from the endoplasmic reticulum chaperone proteins, expressed to protect cellular mechanisms from stress such as hypoxia, insufficient energy and excessive or insufficient substances, and to restore cell homeostasis. In this study, we report a novel pathogenic variant in HYOU1. The proband, the second patient with pathogenic variant in HYOU1, was a female born to consanguineous parents. A novel homozygous pathogenic variant in HYOU1 (NM_001130991.3: c.1456C>T; p.Arg486Cys) was identified, causing anemia, thrombocytopenia and severe panleukopenia and immunodeficiency in the second month of age, leading to consistent high-grade fever, regression of brain functions and recurrent infections; ultimately resulting in the patient expiring at three and half months of age. Both parents are heterozygous for this variant and have no issues related to this study.

Phenotypic spectrum of autosomal recessive Keratitis-Ichthyosis-Deafness Syndrome (KIDAR) due to mutations in AP1B1.

Inborn errors in copper metabolism result in a diverse set of abnormalities such as Wilson disease and MEDNIK syndrome. Homozygous pathogenic variants in AP1B1 lead to KIDAR (Keratitis-Ichthyosis-Deafness Syndrome). The main phenotypic features of KIDAR are ichthyosis, keratitis, erythroderma, and progressive hearing loss accompanied by developmental delay and failure to thrive. Herein, we describe a six-and-a-half-year-old boy with KIDAR caused by a novel pathogenic variant in AP1B1 (NM_001127.4:c.1263C > A, p.Tyr421*). The proband presented with ichthyosis, erythroderma, palmoplantar keratoderma, hearing loss, and corneal scarring. He also had hypotonia, global developmental delay, and photophobia. Lastly, we review all of the previously reported cases and the clinical features associated with KIDAR.

Clinical Features of Okur-Chung Neurodevelopmental Syndrome: Case Report and Literature Review.

Introduction: Autosomal dominant pathogenic variations in the CSNK2A1 gene cause Okur-Chung neurodevelopmental syndrome (OCNDS). Methods: The proband and her parents were examined thoroughly and observed for any issues related to OCNDS. Furthermore, peripheral blood samples were collected from each subject for further investigations. Whole-exome sequencing identified a pathogenic variant in CSNK2A1 (NM_001895: c.62G>A, p.R21Q; rs1402734448). Results: The proband has global developmental delay, speech disorders, epilepsy, and behavioral issues. Despite the previously reported cases, she manifested both atonic and myoclonic seizures simultaneously. Lastly, we provide a review of the reported cases with OCNDS. Discussion: p.R21Q causes OCNDS. Further studies are highly recommended concerning this mutation to validate the results of this study and expand the knowledge regarding CSNK2A1 and the phenotypic spectrum of OCNDS.

Clinical features of patients with Yin Yang 1 deficiency causing Gabriele-de Vries syndrome: A new case and review of the literature.

BACKGROUND: Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in YY1. In this study, we report a 10-year-old boy with a de novo novel pathogenic variant in YY1, the first Iranian patient with Gabriele-de Vries Syndrome. METHODS: The novel de novo pathogenic variant detected in this study (NM_003403:c.690delA, p.Glu231Ilefs*25) was identified by whole-exome sequencing and confirmed by Sanger sequencing. RESULTS: The proband presented with delayed motor and speech development, ataxia, abnormal gait, autistic behavior, brain atrophy, and severe learning disability. Finally, we provide a case-based review of the clinical features associated with Gabriele-de Vries Syndrome. Thus far, merely 13 Gabriele-de Vries Syndrome patients have been reported in the literature. CONCLUSION: The investigations for a suspected case of Gabriele-de Vries Syndrome must involve molecular diagnosis of the disease and its underlying genetic defect because the clinical investigations are generally variable and nonspecific.