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The Neurohospitalist Jul 202422q11.2 microdeletion is the most common microdeletion syndrome in humans with a prevalence of 13 per 100 000 live births, and it is a multisystem condition with...
BACKGROUND
22q11.2 microdeletion is the most common microdeletion syndrome in humans with a prevalence of 13 per 100 000 live births, and it is a multisystem condition with variable phenotypic presentations.
METHODS
We present a case of an adult patient with Dandy-Walker syndrome who presented to our epilepsy clinic with 2 years of new-onset seizures and cognitive decline and 1 year of psychotic symptoms.
RESULTS
Patient had a non-revealing autoimmune and malignancy work-up. Continuous scalp vEEG study showed bursts of 1-2 Hz generalized fronto-centrally predominant spike or polyspike and slow wave discharges. Several myoclonic jerks were time-locked with the generalized discharges indicative of cortical myoclonus. MRI brain revealed periventricular nodular heterotopia in addition to findings suggestive of Dandy-Walker syndrome. Array-based comparative genomic hybridization demonstrated a 22q11.2 microdeletion seen in 22q11.2 deletion syndrome.
CONCLUSION
Our case illustrates the challenges of diagnosing genetic disorders in adults especially when the initial diagnosis is dependent on a number of factors, including the patient's age, the severity of the phenotypic features, and the awareness of the physician.
PubMed: 38895014
DOI: 10.1177/19418744241228618 -
Taiwanese Journal of Obstetrics &... May 2024
Detection of digynic triploidy in a second-trimester fetus presenting syndactyly, relative macrocephaly, intrauterine growth restriction, cardiomegaly, pericardial effusion, Dandy-Walker malformation, double bubble sign and single umbilical artery on prenatal ultrasound and a false negative...
Topics: Humans; Female; Pregnancy; Ultrasonography, Prenatal; Pregnancy Trimester, Second; Pregnancy Trimester, First; Dandy-Walker Syndrome; Adult; Cardiomegaly; Fetal Growth Retardation; Pericardial Effusion; Megalencephaly; Single Umbilical Artery; Triploidy; Abnormalities, Multiple; False Negative Reactions; Noninvasive Prenatal Testing
PubMed: 38802216
DOI: 10.1016/j.tjog.2024.03.014 -
American Journal of Medical Genetics.... Apr 2024Pettigrew syndrome (PGS), an X-linked intellectual disability (XLID), is caused by mutations in the AP1S2 gene. Herein, we described a Thai family with six patients who...
Pettigrew syndrome (PGS), an X-linked intellectual disability (XLID), is caused by mutations in the AP1S2 gene. Herein, we described a Thai family with six patients who had severe-to-profound intellectual impairment, limited verbal communication, and varying degrees of limb spasticity. One patient had a unilateral cataract. We demonstrated facial evolution over time, namely coarse facies, long faces, and thick lip vermilions. We identified a novel AP1S2 variant, c.1-2A>G. The mRNA analysis revealed that the variant resulted in splicing defects with leaky splicing, yielding two distinct aberrant transcripts, one of which likely resulting in the mutant protein lacking the first 44 amino acids whereas the other possibly leading to no production of the protein. By performing a literature review, we found 51 patients and 11 AP1S2 pathogenic alleles described and that all the variants were loss-of-function alleles. The severity of ID in Pettigrew syndrome is mostly severe-to-profound (54.8%), followed by moderate (26.2%) and mild. Progressive spasticity was noted in multiple patients. In summary, leaky splicing found in the present family was likely related to the intrafamilial clinical variability. Our data also support the previous notion of variable expression and neuroprogressive nature of the disorder.
PubMed: 38682877
DOI: 10.1002/ajmg.a.63639 -
Scientific Reports Apr 2024The primary aim of this study was to estimate the incidence of posterior fossa anomalies (PFA) and assess the associated outcomes in King Abdulaziz Medical City (KAMC),...
The primary aim of this study was to estimate the incidence of posterior fossa anomalies (PFA) and assess the associated outcomes in King Abdulaziz Medical City (KAMC), Riyadh. All fetuses diagnosed by prenatal ultrasound with PFA from 2017 to 2021 in KAMC were analyzed retrospectively. PFA included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC), and isolated vermian hypoplasia (VH). The 65 cases of PFA were 41.5% DWM, 46.2% MCM, 10.8% VH, and 1.5% BPC. The annual incidence rates were 2.48, 2.64, 4.41, 8.75, and 1.71 per 1000 anatomy scans for 2017, 2018, 2019, 2020, and 2021, respectively. Infants with DWM appeared to have a higher proportion of associated central nervous system (CNS) abnormalities (70.4% vs. 39.5%; p-value = 0.014) and seizures than others (45% vs. 17.9%; p-value = 0.041). Ten patients with abnormal genetic testing showed a single gene mutation causing CNS abnormalities, including a pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1, and a variant of uncertain significance in the PNPLA8 gene. Our result showed that the most common PFA is DWM and MCM. The autosomal recessive pathogenic mutation is the major cause of genetic disease in Saudi patients diagnosed with PFA.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Retrospective Studies; Dandy-Walker Syndrome; Prenatal Diagnosis; Fetus; Nervous System Malformations; Ultrasonography, Prenatal; Magnetic Resonance Imaging
PubMed: 38600369
DOI: 10.1038/s41598-024-59163-8 -
Child's Nervous System : ChNS :... Jul 2024Meckel-Gruber Syndrome (MKS) is an autosomal recessive genetic disorder, notable for its triad of occipital encephalocele, polycystic renal dysplasia, and postaxial... (Review)
Review
INTRODUCTION
Meckel-Gruber Syndrome (MKS) is an autosomal recessive genetic disorder, notable for its triad of occipital encephalocele, polycystic renal dysplasia, and postaxial polydactyly. Identified by Johann Friederich Meckel in 1822, MKS is categorized as a ciliopathy due to gene mutations. Diagnosis is confirmed by the presence of at least two key features. The condition is incompatible with life, leading to death in the womb or shortly after birth. Recent studies have largely focused on the genetic aspects of MKS, with limited information regarding the impact of neurosurgical approaches, particularly in treating encephaloceles.
METHODS
A systematic review was performed according to the PRISMA statement. The PubMed, Embase, and Web of Science databases were consulted for data screening and extraction, which was conducted by two independent reviewers. The search strategy aimed to encompass studies documenting cases of MKS with published reports of encephalocele excisions, and the search strings for all databases were: Meckel-Gruber syndrome OR Meckel Gruber syndrome OR Meckel-gruber OR Meckel Gruber.
RESULTS
The study included 10 newborns with MKS associated with occipital encephalocele or meningocele, all of whom underwent surgical repair of the occipital sac. The mean gestational age at birth was 36 (± 2) weeks. The mean of birth weight was 3.14 (± 0.85) kilograms. The average head circumference at birth was 33.82 cm (± 2.17). The mean diameter of the encephalocele/meningocele was 5.91 (± 1.02) cm. Other common central nervous system abnormalities included hydrocephalus, Dandy-Walker malformation, and agenesis of the corpus callosum. 40% required shunting for hydrocephalus. Surgery to remove the occipital sac occurred at a median age of 2.5 days (1.5-6.5). The most common post-surgical complication was the need for mechanical ventilation. The most common cause of death was pneumonia and the median age at death was 6.66 (0.03-18) months.
CONCLUSION
Our findings suggest that neurosurgical intervention, especially for managing encephaloceles, may offer some improvement in survival, albeit within a context of generally poor prognosis. However, these results should be interpreted with caution.
Topics: Humans; Encephalocele; Retinitis Pigmentosa; Neurosurgical Procedures; Ciliary Motility Disorders; Polycystic Kidney Diseases; Eye Abnormalities; Infant, Newborn
PubMed: 38459147
DOI: 10.1007/s00381-024-06346-3 -
Clinical Radiology May 2024The prominent retrocerebellar cerebrospinal fluid (CSF) space can be frequently encountered on paediatric neuroimaging studies. In cases involving abnormal vermian... (Review)
Review
The prominent retrocerebellar cerebrospinal fluid (CSF) space can be frequently encountered on paediatric neuroimaging studies. In cases involving abnormal vermian development where imaging does not align with the established criteria of Dandy-Walker malformation (DWM), the term "Dandy-Walker variant or continuum" has been historically employed to describe the aberrant posterior fossa development. Instead, the emphasis is on a more elaborate description of the findings in the posterior fossa. Moreover, combining the findings in the supratentorial brain can occasionally predict certain neurogenetic disorders that mimic Dandy-Walker phenotype. The present review demonstrates and differentiates the imaging features of various entities that result in an enlarged retrocerebellar CSF space, such as inferior vermian hypoplasia (IVH) and several neurogenetic conditions.
Topics: Humans; Child; Dandy-Walker Syndrome; Magnetic Resonance Imaging; Neuroimaging; Head
PubMed: 38429135
DOI: 10.1016/j.crad.2024.01.025 -
JNMA; Journal of the Nepal Medical... Feb 2024Dandy-Walker syndrome is a rare congenital central nervous system malformation. Dandy-Walker variant is characterised by cerebellar vermian hypoplasia, cystic fourth...
UNLABELLED
Dandy-Walker syndrome is a rare congenital central nervous system malformation. Dandy-Walker variant is characterised by cerebellar vermian hypoplasia, cystic fourth ventricular dilatation, and normal posterior fossa volume. Various prenatal tests such as ultrasound, fetal magnetic resonance imaging, and amniocentesis can help diagnose Dandy-Walker syndrome. Here, we report a case of the Dandy-Walker variant with meningitis in a neonate admitted to the neonatal intensive care unit due to multiple petechiae on the anterior abdominal wall, accompanied by peripheral cyanosis at the time of birth. Although maximum cases are diagnosed prenatally, some cases might be missed due to inadequate antenatal examination. Magnetic imaging resonance of the brain is best for the diagnosis of Dandy-Walker syndrome postnatally.
KEYWORDS
case reports; Dandy-Walker malformation, magnetic resonance imaging, meningitis.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Dandy-Walker Syndrome; Brain; Magnetic Resonance Imaging; Meningitis
PubMed: 38409968
DOI: 10.31729/jnma.8472 -
Gynecologie, Obstetrique, Fertilite &... Apr 2024Maternal deaths from indirect obstetric cause result from a preexisting condition or a condition that occurred during pregnancy without obstetric causes but was...
Maternal deaths from indirect obstetric cause result from a preexisting condition or a condition that occurred during pregnancy without obstetric causes but was aggravated by the physiological effects of pregnancy. Twenty-nine deaths with an indirect cause related to a preexisting condition, excluding circulatory diseases or infections, were analysed by the expert committee. Pre-pregnancy pathology was documented in 16 women (epilepsy, n=7; amyloid angiopathy, n=1; Dandy-Walker syndrome, n=1; autoimmune diseases, n=3; diffuse infiltrative pneumonitis, n=1; thrombotic thrombocytopenic purpura, n=1; ovarian cancer in fragile X, n=1; major sickle cell disease, n=1). In 13 women, the pathology was unknown before pregnancy (breast cancer, n=9, epilepsy diagnosed during pregnancy, n=1, brain tumours, n=2 meningioma type, macrophagic activation syndrome, n=1). Death was associated with neoplastic or tumour pathology in 13 women (45%). At the same time, epilepsy was responsible for the death of 8 women (27%), making it the most common cause of death. For both neoplasia and epilepsy, about 50% of deaths were preventable, mainly due to undiagnosed and/or delayed treatment in the case of cancer and failure to monitor or adjust treatment in the case of epilepsy. Pre-conception counselling is therefore strongly recommended if a woman has a known chronic medical condition prior to pregnancy. Finally, if there is a family history of breast cancer, a breast examination is strongly recommended from the first visit during pregnancy, and any breast lumps should be investigated as soon as possible to avoid delaying appropriate treatment.
Topics: Pregnancy; Female; Humans; Maternal Death; Cardiovascular Diseases; Maternal Mortality; Stroke; France; Epilepsy; Breast Neoplasms
PubMed: 38373491
DOI: 10.1016/j.gofs.2024.02.013 -
Cureus Jan 2024Dandy-Walker malformation or syndrome is a rare congenital deformity in which the cerebellar vermis is hypoplastic and upwardly rotated, the fourth ventricle enlarged,...
Dandy-Walker malformation or syndrome is a rare congenital deformity in which the cerebellar vermis is hypoplastic and upwardly rotated, the fourth ventricle enlarged, and the posterior fossa cystically dilated. It represents the most common type of posterior fossa malformations that are usually diagnosed before the age of one year old. We present a seven-year-old boy with a history of neonatal hypotonia and delayed walking, who presented with speech and language difficulties. His physical examination and cognitive tests were unremarkable. The patient's brain magnetic resonance imaging showed a partial defect of the inferior part of the cerebellar vermis and communication between a normal-sized cisterna magna and the fourth ventricle. There were no other coexisting central nervous system or systemic anomalies. This isolated inferior vermian hypoplasia was compatible with an uncommon variant of the Dandy-Walker syndrome. The aim of this report is to provide insight into the importance of implementing a pediatrician-psychiatrist collaboration in the clinical decision-making process of such developmental delay cases. What makes the present case further interesting are the new-onset unprovoked seizures that developed and recurred in the setting of such isolated and less severe posterior fossa anomaly, raising both diagnostic and therapeutic challenges.
PubMed: 38264175
DOI: 10.7759/cureus.52802 -
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