Susan Blaser

SickKids · Department of Diagnostic Imaging

Objective/hypothesis: Sensorineural hearing loss (SNHL) is a common sequela of congenital cytomegalovirus (cCMV), potentially exacerbating neurocognitive delay. The objectives of this study were to assess: (1) age at which SNHL in children with cCMV; (2) stimulability of the auditory system in children with cCMV following cochlear implantation (CI...

Background and purpose: Achieving a specific diagnosis in leukodystrophies is often difficult due to clinical and genetic heterogeneity. Mitochondrial defects cause 5%-10% of leukodystrophies. Our objective was to define MR imaging features commonly shared by mitochondrial leukodystrophies and to distinguish MR imaging patterns related to specific...

Defects in PEX3 are associated with a severe neonatal-lethal form of Zellweger spectrum disorder. We report two moderately affected siblings whose clinical and biochemical phenotypes expand the reported spectrum of PEX3-related disease. Genome sequencing of an adolescent male with progressive movement disorder, spasticity and neurodegeneration, and...

Background and purpose: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan-related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric...

Objectives: To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies. Methods: Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were rev...

Objectives: Ectopic thymus is rare and can be a diagnostic challenge. This study evaluated the management of children radiographically diagnosed with ectopic cervical thymus. Methods: A retrospective review of 100 patients was performed. Data related to clinical presentation, radiological imaging, pathology, and management were collected. Change...

Objectives: To determine prevalence and risk factors for brain injury in infants with critical congenital heart disease (CHD) from 2 sites with different practice approaches who were scanned clinically. Study design: Prospective, longitudinal cohort study (2016-2017) performed at Hospital for Sick Children Toronto (HSC) and Wilhelmina Children's...

Arthrogryposis multiplex congenita (AMC) refers to an aetiologically heterogenous condition, which consists of joint contractures affecting two or more joints starting prenatally. The incidence is approximately 1 in 3000 live births; however, the prenatal incidence is higher, indicating a high intrauterine mortality. Over 320 genes have been implic...

Background: Brain injury, impaired brain growth and long-term neurodevelopmental problems are common in children with transposition of the great arteries (TGA). We sought to identify clinical risk factors for brain injury and poor brain growth in infants with TGA undergoing the arterial switch operation, and to examine their relationship with neur...

Objectives Fetal spina bifida is associated with progressive hydrocephalus, leading to postnatal ventriculoperitoneal shunting. The aim of this study was to document the evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with spina bifida and to assess whether fetal surgery had a measurable impact on ventricular s...

Objectives/Hypothesis There is no consensus on the necessary preoperative imaging in children being evaluated for cochlear implantation (CI). Dual‐imaging protocols that implement both magnetic resonance imaging (MRI) and high resolution computed tomography (HRCT) create diagnostic redundancy in the face of potentially unnecessary radiation and ana...

Newborns with cystic degeneration with or without intractable seizures should be investigated for inborn errors of metabolism, including molybdenum cofactor deficiency (MoCoD). MoCoD may present with non-specific hypoxic ischemic injury in the neonatal period with MRI showing extensive prenatally acquired cystic encephalomalacia involving grey and...

Objective: Fetal myelomeningocele (fMMC) surgery improves infant outcomes when compared with postnatal surgery. Surgical selection criteria and the option of pregnancy termination, however, limit the number of cases that are eligible for prenatal surgery. We aimed to quantify what proportion of cases could ultimately benefit from fetal therapy. M...

LonP1 is crucial for maintaining mitochondrial proteostasis and mitigating cell stress. We identified a novel homozygous missense LONP1 variant, c.2282 C > T, (p.Pro761Leu), by whole-exome and Sanger sequencing in two siblings born to healthy consanguineous parents. Both siblings presented with stepwise regression during infancy, profound hypotonia...

RAC3 is an underexamined member of the Rho GTPase gene family that is expressed in the developing brain and linked to key cellular functions. De novo missense variants in the homolog RAC1 were recently associated with developmental disorders. In the RAC subfamily, transforming missense changes at certain shared residues have been observed in human...

Objectives/Hypothesis To investigate the cochleovestibular apparatus bilaterally in children with isolated unilateral bony cochlear nerve canal (bCNC) stenosis. Study Design Retrospective review. Methods Imaging studies of children with unilateral bCNC stenosis (<1.0 mm) on computed tomography imaging (N = 36) were compared with controls imaged d...

Warsaw breakage syndrome (WBS) is a recently recognized DDX11-related rare cohesinopathy, characterized by severe prenatal and postnatal growth restriction, microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing loss. Only seven cases have been reported in the English literature, and thus the information on the phenotype a...

Objective: To evaluate for temporal bone abnormalities that might affect transmastoid surgery such as cochlear implantation in cases of branchio-oto-renal syndrome (BOR). Study design: Retrospective review. Methods: Qualitative assessment of temporal bone computed tomography imaging was performed by a neuroradiologist for 30 individuals with B...

Rationale: Children with unilateral deafness could have concurrent vestibular dysfunction which would be associated with balance deficits and potentially impair overall development. The prevalence of vestibular and balance deficits remains to be defined in these children. Methods: Twenty children with unilateral deafness underwent comprehensive...

We report the prenatal findings of severe cerebellar growth arrest in two siblings with POLG1 mutations. The first presented with seizures and lactic acidosis immediately after premature birth and was diagnosed with mitochondrial disease on muscle biopsy. Molecular DNA analysis confirmed homozygous missense mutation in the POLG1 gene. The pregnancy...

Purpose of Review Children with unilateral deafness may experience challenges with language development, educational progress, and social interaction. Rehabilitation with a cochlear implant (CI) may minimize these impacts. This review examines the characteristics of children with unilateral deafness presenting for candidacy assessment. Recent Find...

Objective: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations. Methods: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a...

Disorders of brain formation can occur from pathogenic variants in various alpha and beta tubulin genes. Heterozygous pathogenic variants in the beta tubulin isotype A gene, TUBB2A, have been recently implicated in brain malformations, seizures, and developmental delay. Limited information is known regarding the phenotypic spectrum associated with...

Background Likely pathogenic variants in SLC17A5 results in allelic disorders of free sialic acid metabolism including 1) infantile free sialic acid storage disease with severe global developmental delay (GDD), coarse facial features, hepatosplenomegaly and cardiomegaly; 2) intermediate severe Salla disease with moderate to severe GDD, hypotonia, h...

Cleft lip ± cleft palate (CL/P) and cleft palate (CP) are the most common congenital craniofacial abnormalities with an estimated prevalence of 1:690 in the USA [1]. Both conditions can be divided into syndromic (associated with other abnormalities) and non-syndromic (isolated) with about 70 % of the cases with CL/P and 50 % of the cases with CP be...

Mutations of the cystatin B gene (CSTB; OMIM 601145) are known to cause Unverricht-Lundborg disease or progressive myoclonic epilepsy-1A (EPM1A, MIM #254800). Most patients are homozygous for an expanded (>30) dodecamer repeat in the promoter region of CSTB, or are compound heterozygotes for the dodecamer repeat and a point mutation. We report two...

Background: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder associated with leukodystrophy, myeloneuropathy and adrenocortical insufficiency. We performed a retrospective cohort study to evaluate long-term outcome of patients with X-ALD. Method: All patients with X-ALD diagnosed between 1989 and 2012 were included. Electronic pat...

Background: Reduced brain volumes and ischemic injuries are common magnetic resonance imaging (MRI) ndings in infants with congenital heart disease (CHD) both before and after surgery. The aim of this study was to investigate the pattern of brain growth and the prevalence of brain injuries in a large cohort of newborns with single ventricle physiol...

Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg(2+)-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegener...

Purpose: Proton magnetic resonance spectroscopy (MRspec), one of the very few techniques for in vivo assessment of neuro-metabolic profiles, is often complicated by lack of standard population norms and paucity of computational tools. Methods: 7035 scans and clinical information from 4430 pediatric patients were collected from 2008 to 2014. Scan...

Post translational protein modifications exponentially expand the functional complement of proteins encoded by the human genome. One such modification is the covalent addition of a methyl group to arginine or lysine residues, which is used to regulate a substantial proportion of the proteome. Arginine and lysine methylation are catalyzed by protein...

Introduction Infantile neuroaxonal dystrophy (INAD), an autosomal recessive neurodegenerative disorder due to PLA2G6 mutation, is classified both as a PLA2G6-associated neurodegeneration (PLAN) disorder and as one of the neurodegeneration with brain iron accumulation (NBIA) disorders. Age of onset and clinical presentation in INAD is variable. Typi...

Cochlear implantation has become a mainstay of treatment of the profoundly deaf child. Experienced implant surgeons now have the skills to safely manage many medical and radiological factors that once precluded implantation. The current chapter focuses on experience and evidence based management principles related to specific challenging medical an...

N.M. Young, K. Iler Kirk (Eds.) Pediatric Cochlear Implantation ▶ Educates clinicians in the field of pediatric cochlear im-plantation as to the current and emerging best practices ▶ Expands upon the current literature regarding the role of cognition and executive function in pediatric cochlear implant outcomes ▶ Aimed at neurotologists and pediatr...

Leukodystrophies were defined in the 1980s as progressive genetic disorders primarily affecting myelin of the central nervous system. At that time, a limited number of such disorders and no associated gene defects were known. The majority of the leukodystrophy patients remained without a specific diagnosis. In the following two decades, magnetic re...

Data S1. MRI protocol. Data S2. EEG background patterns. Data S3. Partial Least Squares analysis.

Evaluation of imaging studies of the cerebellum in inherited neurodegenerative disorders is aided by attention to neuroimaging patterns based on anatomic determinants, including biometric analysis, hyperintense signal of structures, including the cerebellar cortex, white matter, dentate nuclei, brainstem tracts, and nuclei, the presence of cysts, b...

Objective To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity. Methods We studied a prospective cohort of 20 neonates with CHD who underwent continuous EEG monitoring before surgery to assess funct...

Objective: To use magnetic resonance imaging (MRI) to assess the extent of mastoid opacification after canal wall up (CWU) cholesteatoma surgery. Materials and methods: Thirty-five children in whom post-operative MRI had been obtained after CWU surgery. Cholesteatoma confined to the meso- and/or epi-tympanum was removed using a transcanal approa...

Objective: To characterise the early tissue changes of post encephaloclastic polymicrogyria in the human fetus. Methods: We identified and reviewed the clinical histories and autopsy pathology of post ischemic fetal cerebral cortical injury at less than 30weeks gestational age (GA). The histology of local cortical abnormalities was examined with...

Objectives/hypothesis: To examine outcomes following midline posterior glossectomy (MPG) plus lingual tonsillectomy (LT) for the treatment of significant obstructive sleep apnea (OSA) in children with Down syndrome (DS). Methods: Patients with DS who had persistent OSA following tonsillectomy and adenoidectomy (TA) and were relatively intolerant...

Objective: To investigate preoperative cerebral hemodynamics in newborns with congenital heart disease. We hypothesized that cerebral blood flow and oxygen delivery would be decreased in newborns with congenital heart disease compared with controls. Methods: Using a "feed-and-sleep" approach to performing neonatal magnetic resonance imaging, we...

Lateral meningocele syndrome (LMS), or Lehman syndrome, is a rare disorder characterized by multiple lateral spinal meningoceles, distinctive facial features, joint hypermobility and hypotonia, along with skeletal, cardiac, and urogenital anomalies. Heterozygous NOTCH3 mutations affecting the terminal exon 33 were recently reported as causative in...

Autopsy findings in pontine tegmental cap dysplasia - Volume 42 Issue S3 - Andrew Gao, Susan Blaser, David Chitayat, Felice D’Arco, Patrick Shannon

Aim: To study neuroradiological features in pediatric patients with corpus callosum abnormalities, using new functional subtyping for the corpus callosum, and to correlate the features with the clinical presentation. Method: We performed a retrospective review of 125 patients with radiologically identified abnormalities of the corpus callosum se...

Metabolic diseases affecting the pediatric brain are complex conditions, the underlying mechanisms leading to structural damage are diverse and the diagnostic imaging manifestations are often non-specific; hence early, sensitive and specific diagnosis can be challenging for the radiologist. However, misdiagnosis or a delayed diagnosis can result in...

Abnormal skull shape resulting in craniofacial deformity is a relatively common clinical finding, with deformity either positional (positional plagiocephaly) or related to premature ossification and fusion of the skull sutures (craniosynostosis). Growth restriction occurring at a stenosed suture is associated with exaggerated growth at the open sut...

Two siblings with hypertrophic cardiomyopathy and brain atrophy were diagnosed with Complex I deficiency based on low enzyme activity in muscle and high lactate/pyruvate ratio in fibroblasts. Whole exome sequencing results of fibroblast gDNA from one sibling was narrowed down to 190 SNPs or In/Dels in 185 candidate genes by selecting non-synonymous...

Term neonates with congenital heart disease (CHD) demonstrate a high incidence of white matter injury (WMI), together with increased average diffusivity and decreased fractional anisotropy (FA) on MR diffusion tensor imaging. EEG background activity is a robust measure of functional brain maturation that becomes less discontinuous, contains more fa...

To evaluate the microbiology of pediatric orbital cellulitis in blood cultures and abscess drainage cultures following the introduction of the Haemophilus influenzae serotype b (Hib) vaccine. The medical records of all pediatrics patients (aged <18 years) at a tertiary pediatric hospital during the period January 2000 to July 2011 with a computed t...

Non-progressive cerebellar ataxias are a rare group of disorders that comprise approximately 10% of static infantile encephalopathies. We report the identification of mutations in PMPCA in 17 patients from four families affected with cerebellar ataxia, including the large Lebanese family previously described with autosomal recessive cerebellar atax...

Non-progressive cerebellar ataxias are a rare group of disorders that comprise approximately 10% of static infantile encephalo-pathies. We report the identification of mutations in PMPCA in 17 patients from four families affected with cerebellar ataxia, including the large Lebanese family previously described with autosomal recessive cerebellar ata...

Object: No previous reports exist that have evaluated the relationships of white matter (WM) integrity with the number of shunt revisions, ventricular volume after shunting, and cognition in medically stable children who have spina bifida and hydrocephalus (SBH). The authors hypothesized that enlarged ventricles and a greater number of shunt revis...

Objective: Foetal CT has recently been added to the foetal imaging armamentarium, but this carries with it the risks of ionizing radiation, both to the mother and the foetus. Foetal "black bone" MRI is a new technique that allows assessment of the foetal skeleton without the risk of exposure to ionizing radiation and is a potential new sequence in...

We explored the prevalence of syringomyelia in a series of 113 cases of fetal dysraphism and hindbrain crowding, of gestational age ranging from 17.5 to 34 weeks with the vast majority less than 26 weeks gestational age. We found syringomyelia in 13 cases of Chiari II malformations, 5 cases of Omphalocele/Exostrophy/Imperforate anus/Spinal abnormal...

PRPS1 codes for the enzyme phosphoribosyl pyrophosphate synthetase-1 (PRS-1). The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2). We describe a novel phenotype associated with decreased PRS-1 function in two a...

Purpose To assess the effect of adding orbital computerized tomography (CT) findings to the Chandler criteria for classifying pediatric orbital cellulitis in predicting which patients will require surgical intervention. Methods The medical records of patients with orbital CT at a tertiary pediatric hospital from January 2000 to March 2011 were rev...

Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene encoding α-aminoadipic semialdehyde dehydrogenase. The classic clinical presentation is neonatal seizures responsive only to pyridoxine therapy. White matter abnormalities, corpus callosum agenesis or hypoplasia, megacisterna magna, cortical dysplasia, neuronal heterotop...

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by hypertelorism, bifid uvula, cleft palate and arterial tortuosity. We report on a patient with LDS, bearing mutation in the TGFβR2 gene, whose prenatal examination demonstrated clenched fists and club feet, suggesting arthrogryposis multiplex congenita. P...

To review fetal and maternal outcomes after management of the compromised perinatal airway via operation on placental support (OOPS) or ex utero intrapartum treatment (EXIT). To discuss implications for future management of these complex and rare cases. Retrospective case series of 12 fetuses requiring airway management on placental support at a si...

Mutations in the fukutin-related protein gene account for a broad spectrum of phenotypes ranging from severe congenital muscular dystrophies to a much milder limb-girdle muscular dystrophy 2I. The involvement of the eyes is variable, with most patients having normal eye examination. We describe eye and brain abnormalities in a 16 month-old-boy with...

We analyzed four families that presented with a similar condition characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. We show that recessive mutations in the ASNS gene are responsible for this syndrome. Two of the identified missense mutations dramatically reduce ASNS protein ab...

The aim of this study was to identify clinical and radiological predictors of activities of daily living (ADL) outcomes in children with cerebellar atrophy. Over a period of 5 years, we evaluated 44 participants (25 males, 19 females) children with confirmed cerebellar atrophy using magnetic resonance imaging (MRI). The median age at the time of as...

Infants with phosphomannomutase 2 - congenital disorder of glycosylation (PMM2-CDG), formerly known as CDG1a, present with failure to thrive, visceral dysfunction, thromboembolic events and developmental delays noted before 6 months of age. Diagnosis is often delayed due to the considerable variability in phenotype. Characteristic, but not universa...

Preterm births are increasing in number and while the rates of cerebral palsy have declined, there are increasing numbers of infants who survive with handicaps. In some studies, up to 50 % of children will have morbidity when followed up to school age. A review of current literature was conducted to determine the validity of routine cranial ultraso...

We report on a 46,XY female with pontocerebellar hypoplasia and intellectual disability. To our knowledge, this is the fourth reported patient with this constellation and further confirms a rare new syndrome. The condition is probably a single gene disorder with a currently unknown mode of inheritance. The causative gene is likely involved in the n...

Background and purpose: Diffusion-weighted imaging can be used to characterize brain maturation. MR imaging of the fetus is used in cases of suspected Chiari II malformation when further evaluation of the posterior fossa is required. We sought to investigate whether there were any quantitative ADC abnormalities of the cerebellum in fetuses with th...

Background Thanatophoric dysplasia (TD) and hypochondroplasia are both caused by FGFR3 (fibroblast growth factor receptor 3) gene mutations. Temporal lobe dysplasia has been well described in thanatophoric dysplasia; however, only a couple of anecdotal cases of temporal lobe dysplasia in hypochondroplasia have been described. Objective To define te...

Inherited white-matter disorders are a broad class of diseases for which treatment and classification are both challenging. Indeed, nearly half of the children presenting with a leukoencephalopathy remain without a specific diagnosis. Here, we report on the application of high-throughput genome and exome sequencing to a cohort of ten individuals wi...

To accomplish a diagnosis in patients with a rare unclassified disorder is difficult. In this study, we used magnetic resonance imaging pattern recognition analysis to identify patients with the same novel heritable disorder. Whole-exome sequencing was performed to discover the mutated gene. We identified seven patients sharing a previously undescr...

Individually, metabolic disorders are rare, but overall they account for a significant number of neonatal disorders affecting the central nervous system. The neonatal clinical manifestations of inborn errors of metabolism (IEMs) are characterized by nonspecific systemic symptoms that may mimic more common acute neonatal disorders like sepsis, sever...

Auriculo-condylar syndrome (ACS) is a rare condition affecting first branchial arch structures. The types of hearing loss and temporal bone findings in ACS have not been reported. We describe a 14-year-old male with constricted pinnae, mandibular dysostosis, glossoptosis, a high-arched palate, hearing loss, and cholesteatoma. Computed tomography im...

Complex II deficiency is a rare cause of mitochondrial respiratory chain defects with a prevalence of 2-23%. It is exclusively nuclear encoded and functions in the citric acid cycle by oxidizing succinate to fumarate and in the mitochondrial electron transport chain (ETC) by transferring electrons to ubiquinone. Of the four subunits, SDHA and SDHB...

Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result in defective αDG glycosylation and reduced ligand binding by αDG causing a clinically heterog...

We report on two families with Sengers syndrome and mutations in the acylglycerol kinase gene (AGK). In the first family, two brothers presented with vascular strokes, lactic acidosis, cardiomyopathy and cataracts, abnormal muscle cell histopathology and mitochondrial function. One proband had very abnormal mitochondria with citrate synthase crysta...

We report on two families with Sengers syndrome and mutations in the acylglycerol kinase gene (AGK). In the first family, two brothers presented with vascular strokes, lactic acidosis, cardiomyopathy and cataracts, abnormal muscle cell histopathology and mitochondrial function. One proband had very abnormal mitochondria with citrate synthase crysta...

Congenital infantile myofibromatosis (IM) is a rare mesenchymal disease, presenting with tumors in the skin, muscle, viscera, bone, and subcutaneous tissue. It can present as (a) a solitary form with subcutaneous, erythematous nodules, (b) a multicentric form with subcutaneous, muscle, and/or bony lesions, and (c) a multicentric form with visceral...

PURPOSE/AIM 1. To illustrate important US findings to help in the diagnosis of hypoxic-ischemic injuries (HII) and to correlate these with MRI. 2. To learn and illustrate optimal methods and techniques to depict HII findings on sonography (US). CONTENT ORGANIZATION In the authors’ experience, the head US findings associated with HII may be divided...

We compared neuropsychological profiles in children with shunted hydrocephalus secondary to aqueductal stenosis (AS), a rare form of congenital hydrocephalus, and spina bifida myelomeningocele (SBM), a common form of congenital hydrocephalus. Participants were 180 children with shunted hydrocephalus grouped according to etiology: SBM (n = 151), AS...

Aim: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is known as a relatively mild leukoencephalopathy. We investigated the occurrence of severe variants of LBSL with extensive brain magnetic resonance imaging (MRI) abnormalities. Method: MRIs of approximately 3,000 patients with an unknown leukoenceph...

We report on a child with prenatal onset of overgrowth associated with thick, excessive wrinkled skin and other abnormalities including cleft palate, Chiari malformation and polymicrogyria. His clinical features do not resemble any of the known reported overgrowth syndromes. Genetic evaluations, including karyotype, oligoarray, methylation-sensitiv...