Center Event Calendar

Mark McIntosh,'s picture

Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders.

Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain-hindbrain malformation known as the 'molar tooth sign'. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci.
Author: 
Valente EM
Mark McIntosh,'s picture

Ataxia, intellectual disability, and ocular apraxia with cerebellar cysts: a new disease?

Cerebellar cysts are rare findings in pediatric neuroimaging and rather characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim to report on seven children with cerebellar cysts showing absence of weakness and ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about neurological and ophthalmological features, outcome, and creatine kinase values were collected from clinical histories and follow-up examinations. All MR images were qualitatively evaluated for infra- and supratentorial abnormalities. A SNP 6.0-Array was performed in three children.
Author: 
Boltshauser E
Mark McIntosh,'s picture

Horizontal head titubation in infants with Joubert syndrome: a new finding.

Head thrusts are well documented in Joubert syndrome and ocular motor apraxia. We provide a detailed clinical characterization of head titubation in 13 young children with Joubert syndrome.Detailed characterization of head titubation was assessed by targeted clinical evaluation and/or analysis of videos.In 12 of 13 children (eight males, five females; median age 6y, range 2mo-15y) head titubation was first recognized in the first 2 months of age and decreased in severity until spontaneous resolution.
Author: 
Boltshauser E
Mark McIntosh,'s picture

Mucopolysaccharidoses type I and II: new neuroimaging findings in the cerebellum.

The neuroimaging literature on mucopolysaccharidoses (MPS) is focusing mostly on supratentorial findings. Our study aims to extend the spectrum of neuroimaging findings in patients with MPS focusing on the cerebellum.Twelve patients were included (7 MPS type I and 5 MPS type II). The median age at last MRI was 9.9 years (mean age 10.1 years, range 1.8-28.8 years).
Author: 
Poretti A
Mark McIntosh,'s picture

Congenital abnormalities of the posterior fossa.

The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Nowadays, conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa.
Author: 
Poretti A
Mark McIntosh,'s picture

Differential Diagnosis of Cerebellar Atrophy in Childhood: An Update.

Cerebellar atrophy (CA) is a relatively common, but nonspecific finding in pediatric neurology and neuroradiology. Here, we provide an update of checklists for postnatally acquired CA, unilateral CA, and hereditary CA. In addition, we include a list of disorders with ataxia as a symptom, but without CA. These checklists may help the evaluation of differential diagnosis and planning of additional investigations.
Author: 
Boltshauser E
Mark McIntosh,'s picture

Susceptibility-weighted imaging in pediatric arterial ischemic stroke: a valuable alternative for the noninvasive evaluation of altered cerebral hemodynamics.

SWI provides information about blood oxygenation levels in intracranial vessels. Prior reports have shown that SWI focusing on venous drainage can provide noninvasive information about the degree of brain perfusion in pediatric arterial ischemic stroke. We aimed to evaluate the influence of the SWI venous signal pattern in predicting stroke evolution and the development of malignant edema in a large cohort of children with arterial ischemic stroke.A semiquantitative analysis of venous signal intensity on SWI and diffusion characteristics on DTI was performed in 16 vascular territories.
Author: 
Bosemani T
Mark McIntosh,'s picture

Structural connectivity analysis reveals abnormal brain connections in agenesis of the corpus callosum in children.

Structural connectivity analysis is an ideal tool to study connections in brain malformations. We aimed to characterize the topological network measures and study sub-networks in children with agenesis of the corpus callosum (AgCC). We hypothesized a more segregated structural network in children with AgCC.Structural connectivity analysis including topology analysis and network-based-statistics was applied in children with AgCC and age-matched controls. Probabilistic-tractography and brain segmentation into 108 regions were performed.
Author: 
Poretti A
Mark McIntosh,'s picture

Oral-facial-digital syndrome type VI: is C5orf42 really the major gene?

Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs.
Author: 
Valente EM
Mark McIntosh,'s picture

Cerebellar Hypoplasia and Dysmorphia in Neurofibromatosis Type 1.

Unidentified bright objects (UBO) and tumors are well-known cerebellar abnormalities in neurofibromatosis type 1 (NF1). Literature reports on malformative cerebellar anomalies in neurofibromatosis type 1 (NF1), however, are scant. We retrospectively studied the clinical and neuroimaging findings of 5 patients with NF1 (4 females, age 6 to 29 years at last follow-up) and cerebellar anomalies. Cerebellar symptoms on neurological examination were mild or even not evident whereas learning disabilities were more or less pronounced in four patients.
Author: 
Boltshauser E
Mark McIntosh,'s picture

Diffusion Tractography Biomarkers of Pediatric Cerebellar Hypoplasia/Atrophy: Preliminary Results Using Constrained Spherical Deconvolution.

Advances in MR imaging modeling have improved the feasibility of reconstructing crossing fibers, with increasing benefits in delineating angulated tracts such as cerebellar tracts by using tractography.
Author: 
Battini R
Mark McIntosh,'s picture

Cerebellar Bottom-of-Fissure Dysplasia-a Novel Cerebellar Gray Matter Neuroimaging Pattern.

We report on seven patients with a novel neuroimaging finding that involves exclusively the cerebellar gray matter at the bottom of several fissures of both hemispheres but spares the vermis. The abnormal fissures were predominantly located in the lower and lateral parts of the cerebellar hemispheres. The affected cerebellar cortex was hypointense on T1-weighted and hyperintense on T2-weighted and fluid attenuation inversion recovery sequences. In some patients, the involved cerebellar gray matter was mildly thickened and the affected fissures slightly widened.
Author: 
Boltshauser E
Mark McIntosh,'s picture

Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome).

Cerebellar dysplasia with cysts and abnormal shape of the fourth ventricle, in the absence of significant supratentorial anomalies and of muscular involvement, defines recessively inherited Poretti-Boltshauser syndrome (PBS). Clinical features comprise non-progressive cerebellar ataxia, intellectual disability of variable degree, language impairment, ocular motor apraxia and frequent occurrence of myopia or retinopathy. Recently, loss-of-function variants in the LAMA1 gene were identified in six probands with PBS.
Author: 
Valente EM
Mark McIntosh,'s picture

Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects.

Laminins are heterotrimeric complexes, consisting of α, β and γ subunits that form a major component of basement membranes and extracellular matrix. Laminin complexes have different, but often overlapping, distributions and functions.Under our clinical protocol, NCT00068224, we have performed extensive clinical and neuropsychiatric phenotyping, neuroimaging and molecular analysis in patients with laminin α1 (LAMA1)-associated lamininopathy.
Author: 
Gunay-Aygun M
Mark McIntosh,'s picture

Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes.

Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene.Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses.
Author: 
Valente EM
Mark McIntosh,'s picture

Cerebellar Microstructural Organization is Altered by Complications of Premature Birth: A Case-Control Study.

To compare regional cerebellar microstructure, as measured by diffusion tensor imaging (DTI), between preterm infants at term-equivalent age and healthy term-born control neonates, and to explore associations between DTI findings and clinical risk factors.In this case-control study, DTI studies were performed in 73 premature infants born ≤32 weeks and ≤1500 g birth weight and 73 full-term-born controls from healthy pregnancies.
Author: 
Limperopoulos C
Mark McIntosh,'s picture

Deregulated expression of EZH2 in congenital brainstem disconnection.

Congenital brainstem disconnection (CBSD) is an enigmatic embryo-fetal defect presenting as (sub)total absence of a segment between mesencephalon and lower brainstem. Rostro-caudal limits of the defect vary while the basal pons is always involved and the cerebellum is globally hypoplastic. A recent update and review[1] lists 14 cases, including 3 brain autopsy studies[1-3]. Necrosis and glial- or inflammatory reactions were absent. Inferior olivary nuclei were small or absent, pontine nuclei depleted, and the cerebellar dentate nuclei dysplastic.
Author: 
Baas F

High School Student Volunteers with Project HEAL

Victoria Able, a junior at City Neighbors High School in Baltimore, joins Project HEAL (Health, Education, Advocacy, and Law), Maryland’s only medical-legal partnership, for 10 weeks as a volunteer during the 2016-20

Alicia Vooris, MSPH, In Her Own Words

Alicia Vooris recently completed an internship with the Maryland Center for Developmental Disabilities (MCDD). In her own words, here’s a little bit about what she did and learned during her time with us.

Project HEAL Celebrates 11th Anniversary

Project HEAL (Health, Education, Advocacy, and Law), Maryland’s only medical-legal partnership, celebrated its 11th anniversary on Sept. 8 at Bertha’s restaurant in Fells Point, Baltimore.

MCDD Shares Expertise on Involuntary Psychiatric Admissions Process

Involuntary psychiatric admissions were the focus of a 3.5-hour presentation that Maureen van Stone, associate director of the Maryland Center for Developmental Disabilities (MCDD) and director of

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