Posterior Fossa Malformations Research Articles

Epilepsy in a Moroccan patient with Pitt-Hopkins syndrome

Background : Pitt-Hopkins syndrome (PTHS) is a heterogeneous neurodevelopmental disorder, characterized by intellectual disability, distinctive facial features, and significant autonomic nervous system dysfunction. It is caused by variants in the transcription factor Tcf4. Methods/Observation : We report the first case of PTHS in Morocco, involving a 3-year-old child who presents with the typical features of PTHS, recurrent epilepsy, and a posterior fossa malformation consistent with Dandy-Walker syndrome, along with complete agenesis of the corpus callosum. Standard karyotype analysis and CGH-array confirmed the diagnosis, revealing a de novo terminal deletion of 27.894 kb on the long arm of chromosome 18. High-throughput sequencing is currently underway. Conclusion : Once PTHS is clinically suspected, the diagnosis should be confirmed through molecular genetic testing of the Tcf4 gene. Keywords : Pitt-Hopkins Syndrome, 18q deletion, Tcf4, de Novo, epilepsy.

An Unusual Case of Cerebellar Tonsillar Descent till C7 Vertebrae in a Case of Chiari Malformation with Meningomyelocele

AbstractArnold–Chiari or Chiari malformations are a group of posterior fossa malformations that include the pons, medulla, and cerebellum. This group of disorders may consist of associated abnormalities like myelomeningocele and encephalocele. Chiari malformation has been classified majorly into four categories. Chiari I malformation has been defined as tonsillar descent more than 5 mm below the level of the foramen magnum. The maximum descent of tonsillar herniation reported is 27 mm below the foramen magnum around the C2 vertebrae. In this study, we report the case of a 4-month-old infant with swelling over the lumbosacral (LS) spine since birth with a gradually progressive increase in head size since the age of 2 months. The infant had occasional stridor with respiratory distress for 2 months. Magnetic resonance imaging (MRI) of the brain and spine revealed gross hydrocephalous with myelomeningocele at the L1–L5 level with associated Chiari malformation. The tonsillar descent was almost at the level of C7, which was unusual in his patient. The infant underwent a right ventriculoperitoneal shunt placement and myelomeningocele repair. It was decided that the malformation would be managed in the second sitting. The postoperative period was uneventful and the respiratory distress improved. Cases of tonsillar descent (Chiari I malformation) to the C7 vertebral level are very rare.

Infant Hydrocephalus.

Hydrocephalus is a neurosurgical condition that is highly prevalent in pediatric medicine. In the infant population, there is a distinct set of features that all primary pediatricians would benefit from understanding. Infant hydrocephalus can present prenatally on imaging and postnatally with symptomatic enlargement of the head and associated skull features and raised intracranial pressures. The 2 major pathophysiology models of infant hydrocephalus are the bulk flow and the intracranial pulsatility models. The most common acquired forms of hydrocephalus include posthemorrhagic hydrocephalus, postinfectious hydrocephalus, and brain tumor. The most common congenital forms of hydrocephalus include those due to myelomeningocele, aqueductal stenosis, and posterior fossa malformations. There are various evaluation and treatment algorithms for these different types of hydrocephalus, including cerebrospinal fluid shunting and endoscopic third ventriculostomy. The aim of this review was to elaborate on those features of hydrocephalus to best equip primary pediatricians to diagnose and manage hydrocephalus in infants.

Long-term clinical and radiological trajectories of craniocervical vasculopathy in children with PHACE syndrome.

To describe the rates of stroke and craniocervical vasculopathy progression in children with posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, and eye abnormalities (PHACE) syndrome. A single-center, retrospective natural history study of children with PHACE syndrome. Clinical and sequential neuroimaging data were reviewed to study the characteristics and progression of vasculopathy and calculate the rates of arterial ischemic stroke (AIS) and transient ischemic stroke (TIA). Vasculopathy progression was defined as worsening or new vascular findings on follow-up magnetic resonance angiography. Thirty-four children with cerebrovascular abnormalities at the PHACE syndrome diagnosis were studied (age range = 2 to 18 years, 85% females). Median age at the initial diagnosis was 5.5 months (interquartile range = 1-52 months); median age at the last follow-up was 8 years 6 months (range = 2-18 years). Overall, 10 (29%) patients had radiological progression of their vasculopathy, with a cumulative progression-free rate of 73% (95% confidence interval [CI] = 0.57-0.89), and a cumulative TIA-free and AIS-free rate of 87% (95% CI = 0.745-0.99). Vasculopathy was continuously progressive in six patients (18%) at the last follow-up. Three patients (9%) had TIA and all had progressive vasculopathy. One patient had presumed perinatal AIS at the initial PHACE diagnosis, while no other patient experienced an AIS during the follow-up. In children with PHACE syndrome, craniocervical vasculopathy is non-progressive and asymptomatic in the majority of cases. The risk of ischemic stroke in these children is very low. Larger and prospective studies are necessary to confirm these findings.

'Choroid bar': easy-to-seek marker of normal posterior fossa at 12-14 weeks' gestation.

Our objectives were: (1) to assess the visualization rate of the choroid bar in a consecutive series of 306 first-trimester scans; (2) to verify, in this cohort of fetuses, the normality of the posterior fossa later in pregnancy; and (3) to confirm the non-visualization of the choroid bar in a retrospective series of fetuses with posterior fossa malformations. This study included a prospective and a retrospective series. The former comprised 306 fetuses undergoing routine obstetric ultrasound at our unit in both the first and second trimesters over a 6-month period, while the latter comprised 12 cases of posterior fossa malformations. In the prospective study, the presence of the choroid bar, which is defined as a visually continuous, homogeneously hyperechogenic, thick structure bridging the cisterna magna from side to side, was evaluated at the end of the first-trimester nuchal translucency scan. In the retrospective study, previously acquired three-dimensional volume datasets were processed in order to assess whether the choroid bar could be visualized in cases of open spinal dysraphisms and vermian cystic anomalies. In the prospective study, confirmation of a normal posterior fossa was based on the sonographic features of this anatomical region at the time of the second-trimester anomaly scan at 19-21 weeks' gestation, while, in the retrospective study, it was based on autopsy results, when available, or further direct imaging of the defect later in pregnancy. In the prospective study, the choroid bar could be visualized in all 306 fetuses, on transabdominal ultrasound in 287 (93.8%) cases and on transvaginal ultrasound in 19 (6.2%) cases. The choroid bar was displayed with a ventral/dorsal approach in 67 (21.9%) cases, with a lateral approach in 56 (18.3%) cases and with both in 183 (59.8%) cases. All 306 cases were confirmed to have a sonographically normal posterior fossa at 19-21 weeks. On the other hand, in the retrospective study, it was not possible to visualize the choroid bar in any of the fetuses with posterior fossa malformations. We have described a new sign, the choroid bar, consistent with a normal posterior fossa at 12-14 weeks' gestation. The choroid bar provides the option of screening for major abnormalities of the posterior fossa, since its absence raises suspicion of both open spinal dysraphisms and posterior fossa cystic malformations. At the same time, it is easy to visualize, as it can be seen with all lines of insonation. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation and Treatment of Patients with Small Posterior Cranial Fossa and Chiari Malformation, Types 0 and 1.

The diagnosis of Chiari I malformation is straightforward in patients with typical signs and symptoms of Chiari I malformation and magnetic resonance imaging (MRI) confirming ≥5 mm of cerebellar tonsillar ectopia, with or without a syrinx. However, in many cases, Chiari I malformation is discovered incidentally on MRI to evaluate global headache, cervical radiculopathy, or other conditions. In those cases, the clinician must consider if cerebellar tonsillar ectopia is related to the presenting symptoms. Surgical decompression of the cerebellar tonsils and foramen magnum in patients with symptomatic Chiari I malformation effectively relieves suboccipital headache, reduces syrinx distension, and arrests syringomyelia progression. Neurosurgeons must avoid operative treatments decompressing incidental tonsillar ectopia, not causing symptoms. Such procedures unnecessarily place patients at risk of operative complications and tissue injuries related to surgical exploration. This chapter reviews the typical signs and symptoms of Chiari I malformation and its variant, Chiari 0 malformation, which has <5 mm of cerebellar tonsillar ectopia and is often associated with syringomyelia. Chiari I and Chiari 0 malformations are associated with incomplete occipital bone development, reduced volume and height of the posterior fossa, tonsillar ectopia, and compression of the neural elements and cerebrospinal fluid (CSF) pathways at the foramen magnum. Linear, angular, cross-sectional area, and volume measurements of the posterior fossa, craniocervical junction, and upper cervical spine identify morphometric abnormalities in Chiari I and Chiari 0 malformation patients. Chiari 0 patients respond like Chiari I patients to foramen magnum decompression and should not be excluded from surgical treatment because their tonsillar ectopia is <5 mm. The authors recommend the adoption of diagnostic criteria for Chiari 0 malformation without syringomyelia. This chapter provides updated information and guidance to the physicians managing Chiari I and Chiari 0 malformation patients and neuroscientists interested in Chiari malformations.

PHACES syndrome and multi-regional odontodysplasia: a case report.

PHACES syndrome is an acronym for the syndromic presentation of Posterior fossa malformation, Hemangioma, Arterial anomalies, Coarctation of aorta/cardiac defects, Eye abnormalities and Sternal malformations. Infantile hemangiomas are the most common tumors of infancy. Regional odontodysplasia, commonly referred to as "ghost teeth", is a rare localized developmental malformation of enamel and dentin with varying levels of severity that results in unusual clinical and radiographic appearances of affected teeth. This report describes a rare case of a two-year-old Caucasian male diagnosed with PHACES syndrome also presenting with multi-regional odontodysplasia. Ten of twenty teeth were dysplastic. The patient was treated under general anesthesia in a hospital setting. All affected primary teeth were extracted due to sensitivity, abscess and extremely poor long-term prognosis. Moving forward, a long-term interdisciplinary approach will be necessary to address this child's dentition as it develops.

Posterior Cranial Fossa Malformation and Vascular Dysplasia in GJB2 Gene Mutation.

Posterior Cranial Fossa Malformation and Vascular Dysplasia in GJB2 Gene Mutation.

Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature

BackgroundKBG syndrome is caused by haploinsufficiency of ANKRD11 and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures....

Fetal Neurology: From Prenatal Counseling to Postnatal Follow-Up.

Brain abnormalities detected in fetal life are being increasingly recognized. Child neurologists are often involved in fetal consultations, and specific fetal neurology training has been implemented in many countries. Pediatric neurologists are asked to examine the data available and to contribute to the definition of the long-term outcomes. Ventriculomegaly, posterior fossa malformations, and agenesis/dysgenesis of corpus callosum are among the most common reasons for antenatal neurological consultations. Fetuses with central nervous system and extra-CNS anomalies should ideally be managed in secondary/tertiary hospitals where obstetricians who are experts in fetal medicine and pediatric specialists are available. Obstetricians play a critical role in screening, performing detailed neurosonography, and referring to other specialists for additional investigations. Clinical geneticists are frequently asked to propose diagnostic tests and counsel complex fetal malformations whose phenotypes may differ from those during postnatal life. Advances in fetal MRI and genetic investigations can support the specialists involved in counseling. Nevertheless, data interpretation can be challenging, and it requires a high level of expertise in a multidisciplinary setting. Postnatally, child neurologists should be part of an integrated multidisciplinary follow-up, together with neonatologists and pediatricians. The neurodevelopmental outcomes should be assessed at least up to school age. Children should be evaluated with formal tests of their gross motor, cognitive, language, fine motor/visuo-perceptual skills, and their behavior. In this perspective, fetal neurology can be regarded as the beginning of a long journey which continues with a prolonged, structured follow-up, support to the families, and transition to adult life. A review of the most common conditions is presented, along with the long-term outcomes and a proposal of the neurodevelopmental follow-up of children with CNS malformation which are diagnosed in uterus.

Vascular Anomaly Syndromes in the ISSVA Classification System: Imaging Findings and Role of Interventional Radiology in Management.

Vascular anomalies encompass a spectrum of tumors and malformations that can cause significant morbidity and mortality in children and adults. Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system is strongly recommended for consistency. Vascular anomalies can occur in isolation or in association with clinical syndromes that involve complex multifocal lesions affecting different organ systems. Thus, it is critical to be familiar with the differences and similarities among vascular anomalies to guide selection of the appropriate imaging studies and possible interventions. Syndromes associated with simple vascular malformations include hereditary hemorrhagic telangiectasia, blue rubber bleb nevus syndrome, Gorham-Stout disease, and primary lymphedema. Syndromes categorized as vascular malformations associated with other anomalies include Klippel-Trenaunay-Weber syndrome, Parkes Weber syndrome, Servelle-Martorell syndrome, Maffucci syndrome, macrocephaly-capillary malformation, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis, skeletal, and spinal anomalies) syndrome, Proteus syndrome, Bannayan-Riley-Ruvalcaba syndrome, and CLAPO (capillary malformations of the lower lip, lymphatic malformations of the face and neck, asymmetry of the face and limbs, and partial or generalized overgrowth) syndrome. With PHACES (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects and/or coarctation of the aorta, eye abnormalities, and sternal clefting or supraumbilical raphe) syndrome, infantile hemangiomas associated with other lesions occur. Diagnostic and interventional radiologists have important roles in diagnosing these conditions and administering image-guided therapies-embolization and sclerotherapy, and different ablation procedures in particular. The key imaging features of vascular anomaly syndromes based on the 2018 ISSVA classification system and the role of interventional radiology in the management of these syndromes are reviewed. Online supplemental material is available for this article. ©RSNA, 2022.

Challenges in the pre- and post-natal diagnosis of posterior fossa cysts: A case report and review of historical evolution of descriptive terminologies.

Radiological diagnoses of posterior fossa cystic abnormalities during antenatal and postnatal periods pose significant challenges as they may have similar early imaging features. Some of the frequently described entities are arachnoid cysts and Dandy-Walker malformations. Blake's pouch cyst is relatively underdiagnosed. The main aim of the study was to explore these diagnostic challenges in the context of various descriptive terminologies and their prognostic implications. We illustrate this through our case, where fetal magnetic resonance imaging (MRI) at 36 weeks gestation showed small right cerebellum without hydrocephalus or hemorrhage. Possible differential diagnoses included Dandy-Walker malformation or posterior fossa malformations, facial hemangiomas, arterial anomalies, cardiac and eye anomalies, sternal clefting, and supraumbilical raphe. Postnatal sonography noted posterior fossa cyst without hydrocephalus in a normal term infant, who went on to develop symptomatic hydrocephalus by 15 weeks. Computed tomography brain scan confirmed large subtentorial posterior fossa cyst and extensive internal hydrocephalus. Despite emergent ventriculoperitoneal shunt insertion, head circumference continued to rise. MRI scan showed persistent cyst. Subsequently, infant underwent endoscopic fenestration of the cyst with balloon septostomy and now has an age appropriate developmental profile. There is considerable discordance between antenatal and postnatal neuroimaging findings as highlighted in our case. Diagnostic conundrum here was whether this was an arachnoid or Blake's pouch cyst. Differentiating between posterior fossa fluid collections is crucial for management, prognosis, and parental counseling. Close postnatal follow-up is essential to avert complications due to acute hydrocephalus.

Fetal Brain Development: Regulating Processes and Related Malformations.

This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic–fetal central nervous system (CNS). The processes are described according to the developmental timetable: dorsal induction, ventral induction, neurogenesis, neuronal migration, post-migration neuronal development, and cortical organization. We review the current literature on CNS malformations associated with these regulating processes. We specifically address neural tube defects, holoprosencephaly, malformations of cortical development (including microcephaly, megalencephaly, lissencephaly, cobblestone malformations, gray matter heterotopia, and polymicrogyria), disorders of the corpus callosum, and posterior fossa malformations. Fetal ventriculomegaly, which frequently accompanies these disorders, is also reviewed. Each malformation is described with reference to the etiology, genetic causes, prenatal sonographic imaging, associated anomalies, differential diagnosis, complimentary diagnostic studies, clinical interventions, neurodevelopmental outcome, and life quality.

Ophthalmic involvement in PHACES syndrome: prevalence, spectrum of anomalies, and outcomes

To highlight prevalence, spectrum of anomalies, and outcome of ophthalmic involvement in PHACES syndrome (posterior fossa malformations, infantile hemangiomas, arterial, cardiac, eye, and sternal anomalies). A retrospective, noncomparative, single-institution observational case series of children with PHACES was conducted from 2000 to 2019. Data on ocular presentations, interventions and visual outcomes were collected. Primary outcome measures were the frequency and spectrum of ocular involvement. Secondary outcomes were final visual acuity, long-term ocular sequelae, and frequency of surgical interventions. A total of 43 infants had PHACES, of whom 29 (67%) had periocular infantile facial hemangiomas (IFH) and 6 (14%) had primary ocular anomalies that were always ipsilateral to the IFH. Five patients (12%) met ocular PHACES-specific diagnostic criteria, including optic nerve (3), retinal vascular (1) and lenticular (2) anomalies. Non-PHACES-specific abnormalities were Peters anomaly (1), persistent pupillary membranes (2), dysmorphic optic nerves (1), and iris/choroidal hemangiomas (2). IFH-related periocular abnormalities were frequent: ptosis (29), proptosis (9), strabismus (6). Surgery was required in 8 of the 29 children: (strabismus [6], entropion [2], ptosis [2], and optical iridectomy [1]), all of whom had orbital/conjunctival hemangioma (P = 0.03). Final visual acuity (follow-up, 8.7 years) ranged between 20/20 and 20/80 in 26 of 29 patients. All patients with visual acuity worse than 20/200 (3/29 [10%]) had structural anomalies. Two-thirds of infants with PHACES have periocular IFH causing vision compromising complications of amblyopia and strabismus. Structural ocular anomalies exist in 1 of 7 patients and are always ipsilateral to the IFH. Long-term ophthalmic monitoring and management is required, and the majority of patients obtain good visual outcomes.

Suleiman-El-Hattab syndrome: a histone modification disorder caused by TASP1 deficiency.

TASP1 encodes an endopeptidase activating histone methyltransferases of the KMT2 family. Homozygous loss-of-function variants in TASP1 have recently been associated with Suleiman-El-Hattab syndrome. We report six individuals with Suleiman-El-Hattab syndrome and provide functional characterization of this novel histone modification disorder in a multi-omics approach. Chromosomal microarray/exome sequencing in all individuals. Western blotting from fibroblasts in two individuals. RNA sequencing and proteomics from fibroblasts in one individual. Methylome analysis from blood in two individuals. Knock-out of tasp1 orthologue in zebrafish and phenotyping. All individuals had biallelic TASP1 loss-of-function variants and a phenotype including developmental delay, multiple congenital anomalies (including cardiovascular and posterior fossa malformations), a distinct facial appearance and happy demeanor. Western blot revealed absence of TASP1. RNA sequencing/proteomics showed HOX gene downregulation (HOXA4, HOXA7, HOXA1 and HOXB2) and dysregulation of transcription factor TFIIA. A distinct methylation profile intermediate between control and Kabuki syndrome (KMT2D) profiles could be produced. Zebrafish tasp1 knock-out revealed smaller head size and abnormal cranial cartilage formation in tasp1 crispants. This work further delineates Suleiman-El-Hattab syndrome, a recognizable neurodevelopmental syndrome. Possible downstream mechanisms of TASP1 deficiency include perturbed HOX gene expression and dysregulated TFIIA complex. Methylation pattern suggests that Suleiman-El-Hattab syndrome can be categorized into the group of histone modification disorders including Wiedemann-Steiner and Kabuki syndrome.

Cross-sectional evaluation of Spanish-language resources on websites of US dermatology organizations

Cross-sectional evaluation of Spanish-language resources on websites of US dermatology organizations

Profile of central nervous system malformations in children from a tertiary care center in southern India

Abstract Background: Malformations of the central nervous system (CNS) include a wide range of disorders characterized by neurodevelopmental delay and seizures. They are multifactorial in etiology. There is a lack of data in India; hence, this study was planned to study the clinical profile and type of CNS malformations in children. Materials and Methods: This is a retrospective chart review of CNS malformation between January 2018 and December 2018. Details of clinical and laboratory data were analyzed. Results: Of 110 cases, males were 65. The most common age group was 1–5 years accounting for 50%. Various clinical features were developmental delay (72), seizures (58), microcephaly (57), and dysmorphism (28). History of birth asphyxia was present in 12 cases. The various malformations were neuronal migration defects (36.36%); congenital hydrocephalus (24.54%), with aqueductal stenosis being the most common etiology; neural tube defects (13, 11.8%); and posterior fossa malformation (10 of which two were Joubert syndrome). Others were five cases of agenesis of corpus callosum, one case each of hemimegalencephaly and arteriovenous malformation, and four cases of complex mixed malformations. Conclusion: The most common presentation was global developmental delay and seizures. The most common malformation of CNS observed was neuronal migration defect followed by hydrocephalus. They can present as birth asphyxia.

Propranolol response in patients with segmental versus focal facial hemangiomas: A retrospective case-control study

To the Editor: About 10% of infantile hemangiomas (IHs) are located on the face. They can be subdivided into focal facial hemangiomas (FFHs) and segmental facial hemangiomas (SFHs). SFHs are confined to anatomically defined segments and are frequently associated with cerebrovascular and other anomalies1; patients with definite or possible PHACE (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities) syndrome have SFH diameters >5 cm.2 Because their proliferative phase is longer, SFHs frequently require extended periods of treatment.

"Is my baby all right?" Commentary on "The importance of first trimester screening of cranial posterior fossa in predicting posterior fossa malformations which may be identified in the following weeks of gestation" by Ozdemir et al. David N Jackson, MD.

"Is my baby all right?" Commentary on "The importance of first trimester screening of cranial posterior fossa in predicting posterior fossa malformations which may be identified in the following weeks of gestation" by Ozdemir et al. David N Jackson, MD.

Short- and Long-Term Outcomes of Prenatally Diagnosed Dandy-Walker Malformation, Vermian Hypoplasia, and Blake Pouch Cyst.

Dandy-Walker continuum, which includes Dandy-Walker malformation, vermian hypoplasia, and Blake pouch cyst, is among the most commonly diagnosed posterior fossa malformation by fetal magnetic resonance imaging (MRI). The objective of our retrospective study was to evaluate fetal and postnatal MRI scan and clinical outcomes. Seventy-two patients were identified; 40 patients had postnatal imaging and follow-up (7 Dandy-Walker malformation, 26 vermian hypoplasia, and 7 Blake pouch cyst). Although all patients with Dandy-Walker malformation required ventriculoperitoneal shunts and 66% were intubated at birth, none required tracheostomy tube and 2 of 5 surviving children had no neurologic deficits. Vermian hypoplasia was strongly associated with genetic conditions and cardiac malformations; odds of not ambulating normally were 12 times greater if a syndrome or injury was present. Echocardiogram and genetic screening are recommended with vermian hypoplasia. There is a risk for epilepsy in both Dandy-Walker malformation and vermian hypoplasia. Blake pouch cyst can be complicated by hydrocephalus, but outcome is favorable.