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Cureus Oct 2023Dandy-Walker Syndrome (DWS) is a rare congenital neurological condition characterized by cerebellar and posterior fossa malformations, often presenting a variable...
Dandy-Walker Syndrome (DWS) is a rare congenital neurological condition characterized by cerebellar and posterior fossa malformations, often presenting a variable clinical spectrum. Common complications include hydrocephalus, necessitating interventions like ventriculoperitoneal (VP) shunts, and endoscopic third ventriculostomy (ETV). We describe the case of a five-month-old infant conceived through in vitro fertilization (IVF), initially presenting with cold-like symptoms, later diagnosed with DWS. The patient underwent VP shunt placement for hydrocephalus management, with subsequent complications requiring shunt revisions and ETV. Vigilant monitoring and timely interventions were crucial for a favorable outcome, highlighting the challenges in diagnosing and managing DWS and the importance of tailored treatment strategies.
PubMed: 37933337
DOI: 10.7759/cureus.46564 -
ENeurologicalSci Dec 2023The correlation between Down syndrome and Dandy-Walker syndrome is an exceptionally uncommon occurrence. To date, only four cases have been documented. All previously...
The correlation between Down syndrome and Dandy-Walker syndrome is an exceptionally uncommon occurrence. To date, only four cases have been documented. All previously reported cases involved individuals under the age of 37 months, with prenatal or birth diagnoses. Additionally, most of these cases displayed a limited life expectancy and experienced poor developmental outcomes. In this report, we present the first-ever instance of an 11-year-old male patient, previously undiagnosed with Dandy-Walker syndrome, who presented with acute intracranial hypertension. Magnetic Resonance Imaging revealed an active hydrocephalus caused by a Dandy-Walker malformation. The patient's condition was effectively managed through the implementation of a ventriculo-cysto-peritoneal shunt. This case highlights the coexistence of Dandy-Walker syndrome and Down syndrome in an asymptomatic young patient. Furthermore, it demonstrates that active hydrocephalus in such cases can be successfully addressed through either endoscopic third ventriculostomy or ventriculo-cysto-peritoneal shunt procedures.
PubMed: 37928178
DOI: 10.1016/j.ensci.2023.100480 -
Genes Oct 2023Axenfeld-Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. and variants explain the majority of...
Axenfeld-Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. and variants explain the majority of individuals with Axenfeld-Rieger syndrome (ARS) but leave ~30% unsolved. Here, we present pathogenic/likely pathogenic variants in nine families with ARA/ARS or similar phenotypes affecting five different genes/regions. and explained three families each. was recently linked with syndromic cognitive impairment that includes hearing loss, dental defects, ventriculomegaly, Dandy-Walker malformation, skeletal anomalies (hip dysplasia), and other features showing a significant overlap with -ARS. Anterior segment anomalies are not currently associated with , yet our cases demonstrate ARA, congenital glaucoma, corneal neovascularization, and cataracts. The identification of variants, linked with Alagille syndrome, in three separate families with a clinical diagnosis of ARA/ARS highlights the overlapping features and high variability of these two phenotypes. Finally, intragenic variants in , , and an X chromosome deletion encompassing and (linked with ocular and dental anomalies, correspondingly) were identified in three additional cases with ARS. Accurate diagnosis has important implications for clinical management. We suggest that broad testing such as exome sequencing be applied as a second-tier test for individuals with ARS with normal results for sequencing and copy number analysis, with attention to the described genes/regions.
Topics: Humans; Transcription Factors; Homeodomain Proteins; Anterior Eye Segment; Eye Abnormalities; Ubiquitin Thiolesterase
PubMed: 37895297
DOI: 10.3390/genes14101948 -
Cureus Dec 2023Dandy-Walker syndrome (DWS) is a rare congenital brain malformation defined by the presence of an expanded posterior fossa, full or partial absence of the cerebellar...
Dandy-Walker syndrome (DWS) is a rare congenital brain malformation defined by the presence of an expanded posterior fossa, full or partial absence of the cerebellar vermis, and a cystic expansion of the fourth ventricle. We report an 18-month-old girl with DWS presenting with atypical clinical manifestations and unusual symptoms. She initially presented with persistent vomiting and abdominal pain for four days, not responding to antiemetic medication. In addition, she was found to have abnormal postural arching of the back, extension of the lower limbs, and neck extension. MRI and CT head suggested Dandy-Walker syndrome with hydrocephalus (the lateral ventricle, third ventricle, and fourth ventricle are all significantly dilated with evidence of trans-ependymal cerebrospinal fluid permeation, severe compression anterior displacement of the brain stem). The patient underwent urgent, lifesaving right sub-occipital craniotomy, evacuation, and decompression of the posterior fossa cyst and external ventricular drain (EVD) insertion along with left supra-tentorial EVD insertion. A series of brain magnetic imaging and CT brain post-procedure studies showed a significant reduction in the size of the ventricular system and mass effect on the brain stem.
PubMed: 38196410
DOI: 10.7759/cureus.50262 -
Neurology India 2021Hydrocephalus is a neurological disorder with an incidence of 80-125 per 100,000 live births in the United States. The molecular pathogenesis of this multidimensional... (Review)
Review
Hydrocephalus is a neurological disorder with an incidence of 80-125 per 100,000 live births in the United States. The molecular pathogenesis of this multidimensional disorder is complex and has both genetic and environmental influences. This review aims to discuss the genetic and molecular alterations described in human hydrocephalus, from well-characterized, heritable forms of hydrocephalus (e.g., X-linked hydrocephalus from L1CAM variants) to those affecting cilia motility and other complex pathologies such as neural tube defects and Dandy-Walker syndrome. Ventricular zone disruption is one key pattern among congenital and acquired forms of hydrocephalus, with abnormalities in cadherins, which mediate neuroepithelium/ependymal cell junctions and contribute to the pathogenesis and severity of the disease. Given the relationship between hydrocephalus pathogenesis and neurodevelopment, future research should elucidate the genetic and molecular mechanisms that regulate ventricular zone integrity and stem cell biology.
Topics: Cerebral Aqueduct; Genetic Diseases, X-Linked; Humans; Hydrocephalus; Neural Tube Defects
PubMed: 35102976
DOI: 10.4103/0028-3886.332249 -
Surgical Neurology International 2023Dandy-Walker syndrome (DWS) is a well-known developmental anomaly. An occipital meningocele (OMC) is recognized as a malformation that is relatively often associated...
BACKGROUND
Dandy-Walker syndrome (DWS) is a well-known developmental anomaly. An occipital meningocele (OMC) is recognized as a malformation that is relatively often associated with DWS, but the association of DWS with OMC has been reported in approximately 40 cases. We present herein a rare clinical course of DWS with OMC, in which the sac was small at birth and became progressively larger.
CASE DESCRIPTION
A 5-day-old baby boy was referred to our hospital due to OMC. He was born at 33 gestational weeks due to premature rupture of the membranes. He was diagnosed as having DWS associated with OMC. The OMC was covered with skin and its maximum diameter at birth was 3 cm. Magnetic resonance imaging showed an occipital bone defect and continuity of the fourth ventricle, posterior fossa cyst, and OMC sac. The aqueduct was patent, and no hydrocephalus was found. The OMC sac increased progressively with moderate hydrocephalus and reached 7 cm at the age of 54 days when his weight was 2508 g. A cystoperitoneal shunt and repair were performed after sinus venography by contrast computed tomography (CT). At the age of 1 year and 8 months, he had moderate developmental disabilities.
CONCLUSION
In most cases reported, the OMC was relatively small, and large and giant sizes were reported in only six cases. Almost all cases remained the same size as at birth and underwent surgical intervention as early as possible. It was possible to understand the relationship between the occipital bone defect and abnormal running of sinuses such as the superior sagittal sinus, torcular Herophili, and transverse sinus preoperatively from the CT venography (CTV) image. CTV may be an effective and important method for safely performing repair and shunt.
PubMed: 37941619
DOI: 10.25259/SNI_585_2023 -
Orphanet Journal of Rare Diseases Nov 2019This study describes 5 novel variants of 7 KMT2D/KDM6A gene and summarizes the clinical manifestations and the mutational spectrum of 47 Chinese Kabuki syndrome (KS)... (Review)
Review
OBJECTIVE
This study describes 5 novel variants of 7 KMT2D/KDM6A gene and summarizes the clinical manifestations and the mutational spectrum of 47 Chinese Kabuki syndrome (KS) patients.
METHODS
Blood samples were collected for whole-exome sequencing (WES) for 7 patients and their parents if available. Phenotypic and genotypic spectra of 40 previously published unrelated Chinese KS patients were summarized.
RESULT
Genetic sequencing identified six KMT2D variants (c.3926delC, c.5845delC, c.6595delT, c.12630delG, c.16294C > T, and c.16442delG) and one KDM6A variant (c.2668-2671del). Of them, 4 variants (c.3926delC, c.5845delC, c.12630delG, and c.16442delG) in KMT2D gene and the variant (c.2668-2671del) in KDM6A gene were novel. Combining with previously published Chinese KS cases, the patients presented with five cardinal manifestations including facial dysmorphism, intellectual disability, growth retardation, fingertip pads and skeletal abnormalities. In addition, 29.5% (5/17) patients had brain abnormalities, such as hydrocephalus, cerebellar vermis dysplasia, thin pituitary and white matter myelination delay, corpus callosum hypoplasia and Dandy-Walker malformation.
CONCLUSION
In this report, five novel variants in KMT2D/KDM6A genes are described. A subset of Chinese KS patients presented with brain abnormalities that were not previously reported. Our study expands the mutational and phenotypic spectra of KS.
Topics: Abnormalities, Multiple; Asian People; DNA-Binding Proteins; Exome; Face; Hematologic Diseases; Histone Demethylases; Humans; Neoplasm Proteins; Phenotype; Vestibular Diseases
PubMed: 31727177
DOI: 10.1186/s13023-019-1219-x -
Journal of Neurosciences in Rural... May 2012Endoscopic third ventriculostomy (ETV) is considered as a treatment of choice for obstructive hydrocephalus. It is indicated in hydrocephalus secondary to congenital...
Endoscopic third ventriculostomy (ETV) is considered as a treatment of choice for obstructive hydrocephalus. It is indicated in hydrocephalus secondary to congenital aqueductal stenosis, posterior third ventricle tumor, cerebellar infarct, Dandy-Walker malformation, vein of Galen aneurism, syringomyelia with or without Chiari malformation type I, intraventricular hematoma, post infective, normal pressure hydrocephalus, myelomeningocele, multiloculated hydrocephalus, encephalocele, posterior fossa tumor and craniosynostosis. It is also indicated in block shunt or slit ventricle syndrome. Proper Pre-operative imaging for detailed assessment of the posterior communicating arteries distance from mid line, presence or absence of Liliequist membrane or other membranes, located in the prepontine cistern is useful. Measurement of lumbar elastance and resistance can predict patency of cranial subarachnoid space and complex hydrocephalus, which decides an ultimate outcome. Water jet dissection is an effective technique of ETV in thick floor. Ultrasonic contact probe can be useful in selected patients. Intra-operative ventriculo-stomography could help in confirming the adequacy of endoscopic procedure, thereby facilitating the need for shunt. Intraoperative observations of the patent aqueduct and prepontine cistern scarring are predictors of the risk of ETV failure. Such patients may be considered for shunt surgery. Magnetic resonance ventriculography and cine phase contrast magnetic resonance imaging are effective in assessing subarachnoid space and stoma patency after ETV. Proper case selection, post-operative care including monitoring of ICP and need for external ventricular drain, repeated lumbar puncture and CSF drainage, Ommaya reservoir in selected patients could help to increase success rate and reduce complications. Most of the complications develop in an early post-operative, but fatal complications can develop late which indicate an importance of long term follow up.
PubMed: 22865970
DOI: 10.4103/0976-3147.98222 -
Heliyon Jul 2023Axenfeld-Rieger Syndrome (ARS) is comprised of a group of autosomal dominant disorders that are each characterized by anterior segment abnormalities of the eye.... (Review)
Review
Axenfeld-Rieger Syndrome (ARS) is comprised of a group of autosomal dominant disorders that are each characterized by anterior segment abnormalities of the eye. Mutations in the transcription factors or are the most well-studied genetic manifestations of this syndrome. Due to the rarity this syndrome, ARS-associated neurological manifestations have not been well characterized. The purpose of this systematic review is to characterize and describe ARS neurologic manifestations that affect the cerebral vasculature and their early and late sequelae. PRISMA guidelines were followed; studies meeting inclusion criteria were analyzed for study design, evidence level, number of patients, patient age, whether the patients were related, genotype, ocular findings, and nervous system findings, specifically neurostructural and neurovascular manifestations. 63 studies met inclusion criteria, 60 (95%) were case studies or case series. The gene was most commonly found, followed by , then . The most commonly described structural neurological findings were white matter abnormalities in 26 (41.3%) of studies, followed by Dandy-Walker Complex 12 (19%), and agenesis of the corpus callosum 11 (17%). Neurovascular findings were examined in 6 (9%) of studies, identifying stroke, cerebral small vessel disease (CSVD), tortuosity/dolichoectasia of arteries, among others, with no mention of moyamoya. This is the first systematic review investigating the genetic, neurological, and neurovascular associations with ARS. Structural neurological manifestations were common, yet often benign, perhaps limiting the utility of MRI screening. Neurovascular abnormalities, specifically stroke and CSVD, were identified in this population. Stroke risk was present in the presence and absence of cardiac comorbidities. These findings suggest a relationship between ARS and neurovascular findings; however, larger scale studies are necessary inform therapeutic decisions.
PubMed: 37539177
DOI: 10.1016/j.heliyon.2023.e18225 -
Journal of Taibah University Medical... Dec 2022Associations among Down syndrome (DS), Dandy-Walker variant (DWv), pulmonary hypertension (PH) and childhood interstitial lung disease (chILD) are extremely rare....
Associations among Down syndrome (DS), Dandy-Walker variant (DWv), pulmonary hypertension (PH) and childhood interstitial lung disease (chILD) are extremely rare. Several cases of trisomy disorders with Dandy-Walker malformation (DWM) and neurodevelopmental outcomes have been reported. The extent to which moderate to severe pulmonary hypertension with complications of patent ductus arteriosus (PDA), PH and chILD leads to substantial morbidity and mortality in infants with DS and DWM should be studied. We report the case of an ex-premature 15-month-old girl with confirmed DS with DWv, who developed PH and chILD. This is the first case study reporting the complexity of multiple associations involving DS and DWv. This case led to a prognostic dilemma and required compassionate parental counselling because of the child's uncertain future.
PubMed: 36212578
DOI: 10.1016/j.jtumed.2022.05.005