Hydrocephalus Research Articles

Correlations of Birth Defects With Birth Weight and Gestational Age

Objective To analyze the incidence rate of birth defects in infants born at different gestational ages and birth weights,so as to provide a basis for improving the surveillance system and reducing the incidence of birth defects. Methods Data of all perinatal infants born at and after 28 weeks of gestation and within 7 days after delivery in all the hospitals with the obstetrical department from October 1,2003 to September 30,2015 were collected. Results From 2003 to 2015,1 236 937 perinatal infants were monitored,including 10 619 with birth defects (incidence rate of 8.59‰).Among the infants with birth defects identified by the hospital surveillance system of birth defects in Xi'an during the study period,3 306,3 473,and 224 infants showed the birth weights less than 2 500 g,the gestational age within the range of [28,37] weeks,and the gestation age≥42 weeks,respectively.The low birth weight infants showed higher incidence rate of birth defects than the normal birth weight infants (χ2=37 097.79,P<0.001).The premature infants (gestational age<37 weeks) and postterm infants (gestational age≥42 weeks) showed higher incidence rates of birth defects than infants born at normal gestational age (χ2=24 998.24,P<0.001;χ2=196.40,P<0.001).The top five birth defects of low birth weight infants were congenital hydrocephalus,spina bifida,congenital heart disease,anencephaly,and cleft lip and cleft palate.The outcomes of birth defects in normal weight infants and low weight infants were mainly live births (68.60%) and stillbirths (54.72%),respectively,which showed a significant difference (χ2=647.59,P<0.001).The main outcomes of birth defects in the infants born at normal gestation age,postterm infants,and premature infants were mainly live births (77.38%),live births (83.93%),and stillbirths (57.79%),respectively,which showed significant differences (premature infants vs.infants born at normal gestation age: χ2=2 025.08,P<0.001;premature infants vs. postterm infants:χ2=245.39,P<0.001;infants born at normal gestation age vs.postterm infants:χ2=16.28,P=0.001). Conclusions Premature infants,low birth weight infants,and postterm infants showed significantly higher incidence rate of birth defects than the infants born at normal gestation age.The outcomes of birth defects had significant differences between low birth weight infants and normal birth weight infants,between premature infants and infants born at normal gestation age,between premature infants and postterm infants,and between infants born at normal gestation age and postterm infants.

The homozygous pathogenic variant of the POMGNT1 gene identified using whole-exome sequencing in Iranian family with congenital hydrocephalus

BackgroundHydrocephalus is one of the most common pathophysiological disabilities with a high mortality rate, which occurs both congenitally and acquired. It is estimated that genetic components are the etiology for up to 40% of hydrocephalus cases; however, causal mutations identified until now could only explain approximately 20% of congenital hydrocephalus (CH) patients, and most potential hydrocephalus-associated genes have yet to be determined. This study sought to find causal variations in a consanguineous family with four affected children diagnosed with hydrocephalus.Material and methodsIn this study, we evaluated twenty-five members of an extended family consisting of a nuclear family with four affected children resulting from a consanguineous couple and eighteen of their relatives, including one hydrocephalus case. The mother of this family was experiencing her 15th week of pregnancy, and cytogenetic evaluation was performed using amniocentesis to identify fetal chromosomal abnormalities. We conducted whole-exome sequencing (WES) on the genomic DNA of the proband to detect the CH-causing variants, followed by confirmation and segregation analysis of the detected variant in the proband, fetus, and family members through Sanger sequencing.ResultsFollowing the bioinformatic analysis and data filtering, we found a homozygous variant [NM_001243766.2:c.74G>A:p.W25X] within the protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene confirmed by Sanger sequencing in the proband and segregated with the hydrocephalus in the family. The variant was described as pathogenic and regarded as a nonsense-mediated mRNA decay (NMD) due to the premature stop codon, which results in a truncated protein.ConclusionThe results of the current study broadened the mutational gene spectrum of CH and our knowledge of the hydrocephalus etiology by introducing a novel homozygous variant within the POMGNT1 gene, which had never been previously reported solitary in these patients.

The Utilization of Computed Tomography in the Pediatric Emergency Department for Patients With Ventriculoperitoneal Shunts.

Introduction Despite all the advantages of computed tomography (CT) scanning, there is a significant concern due to the rising use of CT scans in children with ventriculoperitoneal (VP) shunts. High doses of radiation are absorbed by patients, raising their chance of acquiring cancer. Evaluating a potential VP shunt malfunction is a frequent encounter in the pediatric emergency room, often necessitating the utilization of a CT scan. This study aims to recognize and quantify the utilization of CTscans in an emergency setting for pediatric patients with a clinical suspicion of VP shunt malfunction. Methods This retrospective chart review was conducted on patients who visited the emergency department with suspected VP shunt malfunction in a pediatric tertiary care hospital (King Abdullah Specialist Children Hospital), Riyadh, Saudi Arabia. The study included the files of children between the years 2018 and 2019. Results A total of 119 children were included; the main indication for VP shunt insertion was congenital hydrocephalus at 46.8% (n=52). The median number of CT scans done per patient was seven (IQR=3-9). CT findings were abnormal among 55.6% (n=60). The univariate analysis examining the impact of different factors on CT findings showed an association between an abnormal CT finding and female gender (P=0.017), younger age (P=0.03), and the presence of a cerebral cyst (P=0.001); however, subsequent multivariate analysis was not significant for any of these factors.Twenty-two point three percent (n=25) of the patients required neurosurgical intervention, and the associated factors with neurosurgical intervention included changes in activity level (P=0.04), weakness (P=0.004), and altered mental status (P=0.001). Conclusion Children with VP shunts are susceptible to significant radiation exposure through the utilization of CT scans whenever they present to the ER with suspected shunt malfunction during their lifespan, which puts them at risk of radiation-related complications, such as cancers. CT imaging remains a helpful tool aiding physicians in making accurate decisions. However, in this study, almost half of the children had unremarkable CT findings. Thus, it is imperative to rationalize its use by establishing tailored guidelines that delineate the appropriate circumstances warranting its application.

Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology.

Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a favorable prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles (EVs), circulating in CSF, express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from PA, congenital hydrocephalus (CH, non-tumor control), or medulloblastoma (MB, unrelated tumoral control) patients. A total of 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which were expressed in the unprocessed total and in its large-EV (LEV), and small-EV (SEV) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted the inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers for discriminating among pilocytic astrocytoma and unrelated tumoral (MB) or non-tumoral conditions in all the fractions examined, and are proposed to be prospectively validated in the plasma for translational medicine applications.

Congenital hydrocephalus in a stillborn Haflinger foal

A 14-year, multiparous Haflinger mare, apparently fullterm (unknown breeding or ovulation date), was presented for dystocia. Mare was transvaginally palpated at the farm by the referring veterinarian; foal was in craniolongitudinal presentation, dorsosacral position with extended forelimbs in the vaginal vault and head just cranial to cervix, and a cranial abnormality of the foal prevented assisted vaginal delivery. Mare was referred. Foal was not alive at presentation and was undeliverable with assistance because of congenital hydrocephalus. Anesthetized mare was placed in Trendelenburg position, controlled vaginal delivery was elected and foal was removed via fetotomy. Mare was negative for β1, 3- N-acetylgalactosaminyltransferase 2 (B3GALNT2) nonsense mutation (reported to be responsible for hydrocephalus). Dystocia in a Haflinger mare because of hydrocephalus is reported for the first time.

A selective defect in the glial wedge as part of the neuroepithelium disruption in hydrocephalus development in the mouse hyh model is associated with complete corpus callosum dysgenesis.

Dysgenesis of the corpus callosum is present in neurodevelopmental disorders and coexists with hydrocephalus in several human congenital syndromes. The mechanisms that underlie the etiology of congenital hydrocephalus and agenesis of the corpus callosum when they coappear during neurodevelopment persist unclear. In this work, the mechanistic relationship between both disorders is investigated in the hyh mouse model for congenital hydrocephalus, which also develops agenesis of the corpus callosum. In this model, hydrocephalus is generated by a defective program in the development of neuroepithelium during its differentiation into radial glial cells. In this work, the populations implicated in the development of the corpus callosum (callosal neurons, pioneering axons, glial wedge cells, subcallosal sling and indusium griseum glial cells) were studied in wild-type and hyh mutant mice. Immunohistochemistry, mRNA in situ hybridization, axonal tracing experiments, and organotypic cultures from normal and hyh mouse embryos were used. Our results show that the defective program in the neuroepithelium/radial glial cell development in the hyh mutant mouse selectively affects the glial wedge cells. The glial wedge cells are necessary to guide the pioneering axons as they approach the corticoseptal boundary. Our results show that the pioneering callosal axons arising from neurons in the cingulate cortex can extend projections to the interhemispheric midline in normal and hyh mice. However, pioneering axons in the hyh mutant mouse, when approaching the area corresponding to the damaged glial wedge cell population, turned toward the ipsilateral lateral ventricle. This defect occurred before the appearance of ventriculomegaly. In conclusion, the abnormal development of the ventricular zone, which appears to be inherent to the etiology of several forms of congenital hydrocephalus, can explain, in some cases, the common association between hydrocephalus and corpus callosum dysgenesis. These results imply that further studies may be needed to understand the corpus callosum dysgenesis etiology when it concurs with hydrocephalus.

Efficacy and safety of bedside percutaneous three-millimeter twist-drill trephination under local anesthesia-a retrospective study of 1000 patients.

Percutaneous 3-mm twist-drill trephination (TDT) under local anesthesia as a bedside operative technique is an alternative to the conventional open surgical trephination in the operating theatre. The aim of this study was to verify the efficacy and safety of this minimal invasive procedure. This retrospective study comprises 1000 patients who were treated with TDT under local anesthesia at bedside due to chronic subdural hematoma (cSDH), intracerebral hemorrhage (ICH), and hydrocephalus (HYD) as a result of subarachnoid hemorrhage or non-hemorrhagic causes, increased intracranial pressure (IIP) in traumatic brain injury or non-traumatic brain edema, and other pathologies (OP) requiring drainage. Medical records, clinical outcome, and results of pre- and postoperative computed tomography (CT) and/or magnetic resonance tomography (MRT) were analyzed. Indications for TDT were cSDH (n = 275; 27.5%), ICH (n = 291; 29.1%), HYD (n = 316; 31.6%), IIP (n = 112; 11.2%), and OP (n = 6; 0.6%). Overall, primary catheter placement was sufficient in 93.8% of trephinations. Complication rate was 14.1% and mainly related to primary catheter malposition (6.2%), infections (5.2%), and secondary hemorrhage (2.7%); the majority of which were clinically inapparent puncture channel bleedings not requiring surgical intervention. The revision rate was 13%. Bedside TDT under local anesthesia has proven to be an effective and safe alternative to the conventional burr-hole operative technique as usually performed under general anesthesia in the operation theatre, and may be particularly useful in emergency cases as well as in elderly and multimorbid patients.

The Child with a Large Head: Cranial Computed Tomography Findings in 123 Nigerian Children with Macrocephaly

Objectives: Differentiation of benign macrocephaly from other etiologies that may require prompt evaluation and intervention is very necessary to prevent long term neurological deficits. Cross-sectional imaging of the brain with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) is recommended in evaluation of such patients. In resource poor-settings, CT is more readily available, hence the objective in this study is to evaluate the spectrum of CT findings in children with macrocephaly in our locality and document the possible etiologic factors that are amenable to surgical intervention.&#x0D; Materials and Methods: This is a retrospective study of pediatric patients with clinical diagnosis of large head/macrocephaly who were evaluated with cranial CT in a tertiary hospital in Abuja from January 2018- June 2022. SAS software (SAS Institute, Cary, North Carolina, USA) version 9.4 was used for database management and analysis with P≤ 0.05 level of significance.&#x0D; Results: One hundred and twenty three children were included in the study with ages ranging from 2 days to 4 years. Majority of the children were males, 74 (60.2%). The predominant age group at presentation was between 0 to 6 months,78 (63.4%). Hydrocephalus was the main cause of macrocephaly in 110 patients (89.4%). Congenital hydrocephalus was predominant in 81 children (73.6%). Communicating hydrocephalus was noted in 44 children (40%) while 62 (56.4%) were non-communicating. The commonest level of obstruction was at the aqueduct of Sylvius and exit foramina in 22 (35.5%) patients each. There was no significant statistical difference between the genders(P=0.920).&#x0D; Conclusion: CT is a veritable tool in the evaluation of the child with a large head with an appreciable number of surgically amenable pathologies noted. Hydrocephalus is the commonest etiology of macrocephaly in our environment with the majority of the cases due to congenital abnormalities.

Navigating Uncharted Waters: Comparative Analysis of Clinical Progression and Outcomes in Vestibular Schwannoma Patients with Papilledema and without Hydrocephalus, Versus Those without Papilledema and Hydrocephalus: A Comprehensive Institutional Insight

Papilledema's association with hydrocephalus (HCP)-linked larger vestibular schwannoma (VS) is established but cases lacking concurrent HCP require further investigation. This retrospective comparative observational study, conducted from July 2018 to July 2023, examined 120 VS patients undergoing surgery. Patients were categorized into Group 1 (papilledema without HCP) and Group 2 (no papilledema or HCP), with comprehensive data analyzed. In this study, Group 1 (14 patients with papilledema) and Group 2 (106 patients without papilledema or HCP) were compared. Group 1 was younger (mean age 27.21±11.73years) than Group 2 (mean age 54.66±11.44years). Both groups had similar symptom durations and tumor detection times. Group 1 had increased vascularity (P= 0.001), elevated cisterna magna protein levels (P= 0.001), and a higher incidence of neurofibromatosis 2 (P= 0.003). They also experienced longer surgeries (P= 0.001) and more blood loss (P= 0.001), leading to extended postoperative complications. Group 2 showed improved postsurgery visual outcomes (P= 0.001), better Glasgow Outcome Scores (P= 0.001), enhanced facial nerve preservation (P= 0.002), and improved hearing on follow-up (P= 0.003). Logistic regression analysis highlighted prolonged surgery duration (P= 0.057) and papilledema (P= 0.0001) as significant factors influencing visual improvement. Patients with VS require preoperative fundoscopy evaluation due to potential visual loss and papilledema, even without HCP. Early treatment initiation enhances visual and hearing outcomes. Meticulous surgery is vital given the lesion's hypervascular nature and adherence to surrounding structures. Preoperative embolization may aid in preserving neurovascular structures. In developing countries with higher blindness rates, judicious noncontrast computed tomography brain evaluation is crucial for timely detection and treatment initiation of lesions like VS.

Concurrent Hydrocephalus and Ulcerative Colitis: Exploring the Role of IL18: A Case Report

The coexistence of fetal hydrocephalus (HC) and ulcerative colitis (UC) within a single patient is exceptionally rare. This paper presents the case of a 4-year-old girl initially diagnosed with congenital hydrocephalus via in-utero ultrasonography at 20 weeks of gestation. Subsequent ventriculoperitoneal (VP) shunt placement was performed, and 3 years later, the patient was histologically and serologically diagnosed with ulcerative colitis. The synchronization of these distinct medical events in the same individual, particularly the interval between the treatments, represents an unprecedented occurrence not previously documented. The report details the patient’s recent presentation of recurrent bloody diarrhea and failure to thrive, which was effectively managed with oral prednisolone and sulfasalazine. Notably, the simultaneous manifestation of these conditions prompts consideration of potential contributing factors, including genetic markers such as interleukin 18 (IL 18), which have been linked to both disorders in existing literature. This case underscores the need for further research to elucidate the genetic and pathological markers, as well as predictors, which may underlie the concurrent occurrence of hydrocephalus and ulcerative colitis. Understanding these complexities could offer valuable insights into the intricate interplay of genetic and environmental factors in the development of such unique medical co-morbidities.

CCDC88C variants are associated with focal epilepsy and genotype-phenotype correlation.

CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in thegnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.

Dental Management of a Child with Hunter’s Syndrome and Hydrocephalus: A Case Report

Mucopolysaccharidosis (MPS) type II, or Hunter’s syndrome, is an X-linked recessive disorder with a defect in Glycosaminoglycan (GAG) metabolism resulting in a deficiency of the enzyme Iduronate sulfatase. Hydrocephalus (HC) is a condition in which the volume of Cerebrospinal Fluid (CSF) in the cerebral ventricles is abnormally elevated. HC patients may show macrocephaly and delayed development. A Ventriculoperitoneal (VP) shunt is the most commonly used treatment option. Hereby, the authors present a case report of a nine-year-old male child diagnosed with Hunter’s syndrome and HC. The manuscript provides a comprehensive overview of the dental management strategies involving a team of specialists, including a paediatric dentist and a paediatrician. Key interventions included emphasising assessment of oral health issues related to the syndrome and condition, modification of treatment plans like implementation of a tailored oral hygiene regimen and fluoride treatments, use of sedative techniques to manage anxiety and facilitate thorough dental work, regular follow-up appointments to monitor oral health and accommodate the child’s physical and developmental needs, preventive care, modified treatment techniques, and close monitoring of systemic health. Effective dental management of patients with HC and Hunter’s Syndrome requires a comprehensive, multidisciplinary approach. Tailoring dental care to accommodate the unique needs of these patients can lead to successful outcomes and improved quality of life. This case underscores the importance of collaboration between dental and medical professionals in managing complex cases.

Peripheral white blood cell patterns in children with hydrocephalus as a response to ventriculo-peritoneal shunt infection.

Shunt infection is one of the most common complications of conventional hydrocephalus treatment. The route of invasion of a pathogen can modify the immune response of the CNS. The aim of the study is to analyze the immune response to shunt infection caused by S. epidermidis in children with hydrocephalus. The immune response to the pathogen will be analyzed on the basis of, inter alia, simple laboratory test results, such as changes in the pattern of white blood cells, including neutrophils, monocytes, and lymphocytes. The entire study analyzes changes in general parameters of the cerebrospinal fluid (pleocytosis, protein level, glucose level) and in levels of selected interleukins (IL-6, CXCL8 / IL-8, CCL3 / MIP-1a) in the cerebrospinal fluid. The clinical material analyzed in the study was collected in 2010-2014. The study group consisted of 30 patients, who were admitted to the hospital due to their first-ever episode of valve dysfunction caused by S. epidermidis infection. The control group consisted of 30 children who also suffered from congenital hydrocephalus but had not been operated on before. The most pronounced response to CSF infection in the study group was a significant increase in the counts of all investigated WBC lines in the samples collected immediately after the patients' admission to the ward. The earliest aberration of the CSF was a significant increase in protein level. An infection of a ventriculoperitoneal shunt caused by S. epidermidis evokes a very early peripheral blood response. In children affected by a ventriculoperitoneal valve infection, the humoral immune response detected in the cerebrospinal fluid precedes the increase in the level of pleocytosis. The highest level of cytokines in the cerebrospinal fluid is achieved when the pathogens are cleared. Phagocytes, and, in particular, monocytes, play an important role in the normalization of the cerebrospinal fluid parameters after the elimination of S. epidermidis. The local immune response of the central nervous system plays an important role in extinguishment of the inflammatory process.

Isolation of Salmonella enterica Serovar Typhi from Infected Intracranial Dermoid Cyst: A Case Report

Salmonella Typhi is a versatile pathogen that can infect almost all organs of its host. There has been an increase in the number of cases of extraintestinal infection caused by Salmonella species during the past decade. Present case is of a 17-year-old immunocompetent female admitted to the hospital with complaints of a general tonic-clonic seizure and diagnosed with a Suprasellar hypodense lesion with Hydrocephalus (HCP) documented on a Computed Tomography (CT) scan of the head. Magnetic Resonance Imaging (MRI) revealed signs of an intracranial dermoid cyst. Placement of a right Ventriculoperitoneal (VP) Shunt was performed, followed by a right craniotomy with decompression, during which 5 mL of pus was collected from the lesion. The pus was received in the Department of Microbiology and subjected to culture, which grew Salmonella enterica serovar Typhi. The patient had been empirically receiving injection cefoperazone-sulbactam 2g/2g twice daily and injection vancomycin 1g 12 hourly before the isolation of Salmonella Typhi. She had also been receiving injection levetiracetam 500 mg i.v. twice a day and inj. phenytoin 500 mg i.v. thrice a day. Following the positive culture report, injection ceftriaxone 2 g daily was started. The patient was discharged on the fifth postoperative day while on injection ceftriaxone, oral levetiracetam 500 mg, and phenytoin 100 mg and was asked to report to the neurosurgery department after seven days for follow-up. On follow-up, she showed improvement, and there were no complaints of fever, seizure, or loss of consciousness. In conclusion, proper clinical, radiological, and microbiological evaluation is very much necessary, and clinicians should be aware of the relatively rare manifestations of Salmonella Typhi infections.

Exome sequence analysis identifies a homozygous, pathogenic, frameshift variant in the MAN2B1 gene underlying clinical variant of α-mannosidosis.

α-mannosidosis (MAN) is a rare genetic condition that segregates in an autosomal recessive manner. Lack of lysosomal alpha-mannosidase is the underlying cause of the disease. Symptoms of the disease gradually worsen with the age. Newborns are usually asymptomatic, however, some cases are reported with either congenital ankle equinus or hydrocephalus during the first year. Primary symptoms are characterized by immune deficiency, hearing loss, skeletal abnormalities, progressive mental, motor and speech functions' impairment followed by facial asymmetry. We studied two Saudi families (A and B) with bilateral moderate hearing loss (family A) and clubfoot with glaucoma (family B). Clinical diagnosis was not reached based on phenotype of patients. Therefore, hypothesis-free whole exome sequencing (WES) was performed on DNA samples from affected individuals of both the families, followed by Sanger sequencing and segregation analysis to validate the segregation of the identified variant. Furthermore, 3D protein modelling was performed to determine the in silico effects of the identified variant on the protein structure and function. Re-examination of clinical features revealed that the patients in family A have speech delay and hearing impairment along with craniostenosis, whereas the patients from family B have only clubfoot and glaucoma. WES identified a well known pathogenic homozygous frameshift variant (NM_000528.4: c.2402dupG; p.S802fs*129) in MAN2B1 in both the families. Sanger sequencing confirmed the segregation of the variant with the disease phenotype in both the families. 3D structural modeling of the MAN2B1 protein revealed significant changes in the tertiary structure of the mutant protein, which would affect enzyme function. This report presents a new case where partial and novel α-mannosidosis phenotypes are associated with a MAN2B1 gene pathogenic variant. Patients in both the families have manifested peculiar set of clinical symptoms associated with α-mannosidosis. Family A manifested partial clinical symptoms missing several characteristic features like intellectual disability, dysmorphic features, neurological and abdominal manifestations, whereas family B has no reported clinical symptoms related to α-mannosidosis except the novel symptoms including club foot and glaucoma which has never been reported earlier The current findings support the evidence that biallelic variants of MAN2B1 are associated with new clinical variants of α-mannosidosis.

Physiotherapeutic management of Hydrocephalus-Ex vacuo: A Case Report

Hydrocephalus Ex-vacuo refers to an elevated volume with no increasing Cerebrospinal Fluid (CSF) pressure, particularly in instances of diminished brain tissue. Since there is no increased intracranial pressure in Hydrocephalus Ex-vacuo, few general symptoms such as irritability, drowsiness, and even larger head presentation can be absent compared to congenital hydrocephalus. The current case study presents a one-year-old male child exhibiting delays in developmental milestones, including poor head and trunk control, associated with a history of prenatal bleeding and subsequent birth complications. Despite a seemingly normal birth, the child experienced postnatal complications such as vomiting, seizures, and abdominal distension, leading to a 15-day Neonatal Intensive Care Unit (NICU) stay. Persistent delays prompted medical consultations, culminating in a referral for physiotherapy following Magnetic Resonance Imaging (MRI) findings indicative of hydrocephalus ex-vacuo. Clinical assessments revealed a restricted range of motion, muscle tightness in the lower extremities, and poor muscle control and reflex persistence. Imaging confirmed ventricular enlargement consistent with Hydrocephalus Ex-vacuo, necessitating targeted physiotherapy interventions. Therapeutic strategies focused on promoting head and trunk control through prone positioning, bolster support, and dynamic exercises utilising physio balls. Progressive interventions facilitated significant improvements within six months, highlighting the efficacy of early rehabilitation and parental involvement in achieving motor milestones. The present case underscores the importance of timely diagnosis, multidisciplinary collaboration, and rehabilitative interventions in optimising outcomes for children with hydrocephalus ex-vacuo. Further research is warranted to explore additional therapeutic modalities and long-term prognostic indicators for this patient population.

Outcomes of Endoscopic Third Ventriculostomy in Cases of Congenital Hydrocephalus Based on MRI CSF Flowmetry and Transcranial Doppler in Infants

Outcomes of Endoscopic Third Ventriculostomy in Cases of Congenital Hydrocephalus Based on MRI CSF Flowmetry and Transcranial Doppler in Infants

"Various factors affecting the success of the ETV procedure in infants"-an insight via a prospective study.

Congenital hydrocephalus in infants treated with ETV has variable results in literature. We studied some supposed clinicoradiological parameters which though are considered vital in deciding operative management and have never been thoroughly studied to establish a well-defined association. To evaluate the influence of clinicoradiological profile and intraoperative findings over the outcome of ETV done in infants for congenital hydrocephalus. All infants who underwent ETV in King George's Medical University, Lucknow, from January 2019 to February 2020 for congenital hydrocephalus were included. Their clinical, radiological, operative data was gathered. Infants were followed at 1, 3, and 6months after ETV. ETV success was defined as stabilization of abnormal head growth with resolution of symptoms of raised ICP and no requirement of shunt surgery 6months post-ETV. All the clinicoradiological and intraoperative factors were statistically correlated with the final outcome. Forty infants were operated for congenital hydrocephalus during the study period in our institution. Failure rate was higher in children younger than 3months (p value of 0.04). Increase in head size was present in all 40 cases and bulging anterior fontanelle in 95% cases. Success rate of ETV at 1, 3, and 6months was 62.5%, 40%, and 35%. Most of failure occurred within 3months after the procedure. Expiry rate at 1, 3, and 6month was 15%, 17.5%, and 17.5%. None of the intraoperative findings significantly correlated with the final outcome. ETV can be a luring treatment of congenital hydrocephalus in infants but has limited success rate because of the dependency of procedure on well-formed arachnoid villi for absorption. It also carries minimal risk of fatal complications like CSF leak and meningitis associated with it. Age is the only factor which truly reflects the outcome of the procedure.

Geometric variability in radiological appearance of third ventricle in congenital hydrocephalus- is it really so pliable? Or do we need to visualize it differently? A two-case study and literature review

Enlargement of third ventricle is seen due to multiple causes, usually associated with hydrocephalus. Raised intracranial pressure (ICP) is the most common indication for a cerebrospinal fluid diversion procedure. However, congenital anomalies like Dandy walker malformation (DWM) may not always manifest with raised ICP. Identifying neurological delay and neurocognitive parameters and correlating this with existing anatomical features is extremely important. We discuss this report of two cases of patients with DWM where abnormal morphology of the third ventricle was analysed and used to interpret clinical neurological delay.

A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus.

Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery in children. Recent studies have implicated SMARCC1, a component of the BRG1-associated factor (BAF) chromatin remodelling complex, as a candidate congenital hydrocephalus gene. However, SMARCC1 variants have not been systematically examined in a large patient cohort or conclusively linked with a human syndrome. Moreover, congenital hydrocephalus-associated SMARCC1 variants have not been functionally validated or mechanistically studied in vivo. Here, we aimed to assess the prevalence of SMARCC1 variants in an expanded patient cohort, describe associated clinical and radiographic phenotypes, and assess the impact of Smarcc1 depletion in a novel Xenopus tropicalis model of congenital hydrocephalus. To do this, we performed a genetic association study using whole-exome sequencing from a cohort consisting of 2697 total ventriculomegalic trios, including patients with neurosurgically-treated congenital hydrocephalus, that total 8091 exomes collected over 7 years (2016-23). A comparison control cohort consisted of 1798 exomes from unaffected siblings of patients with autism spectrum disorder and their unaffected parents were sourced from the Simons Simplex Collection. Enrichment and impact on protein structure were assessed in identified variants. Effects on the human fetal brain transcriptome were examined with RNA-sequencing and Smarcc1 knockdowns were generated in Xenopus and studied using optical coherence tomography imaging, in situ hybridization and immunofluorescence. SMARCC1 surpassed genome-wide significance thresholds, yielding six rare, protein-altering de novo variants localized to highly conserved residues in key functional domains. Patients exhibited hydrocephalus with aqueductal stenosis; corpus callosum abnormalities, developmental delay, and cardiac defects were also common. Xenopus knockdowns recapitulated both aqueductal stenosis and cardiac defects and were rescued by wild-type but not patient-specific variant SMARCC1. Hydrocephalic SMARCC1-variant human fetal brain and Smarcc1-variant Xenopus brain exhibited a similarly altered expression of key genes linked to midgestational neurogenesis, including the transcription factors NEUROD2 and MAB21L2. These results suggest de novo variants in SMARCC1 cause a novel human BAFopathy we term 'SMARCC1-associated developmental dysgenesis syndrome', characterized by variable presence of cerebral ventriculomegaly, aqueductal stenosis, developmental delay and a variety of structural brain or cardiac defects. These data underscore the importance of SMARCC1 and the BAF chromatin remodelling complex for human brain morphogenesis and provide evidence for a 'neural stem cell' paradigm of congenital hydrocephalus pathogenesis. These results highlight utility of trio-based whole-exome sequencing for identifying pathogenic variants in sporadic congenital structural brain disorders and suggest whole-exome sequencing may be a valuable adjunct in clinical management of congenital hydrocephalus patients.