Publications by authors named "Amy Armstrong-Javors"

7 Publications

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MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia.

Ann Neurol 2021 Jan 14. Epub 2021 Jan 14.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.

The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. ANN NEUROL 2021.
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http://dx.doi.org/10.1002/ana.26019DOI Listing
January 2021

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder.

Genet Med 2021 Feb 11;23(2):384-395. Epub 2020 Nov 11.

Institute of Human Genetics, Technical University Munich, Munich, Germany.

Purpose: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).

Methods: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.

Results: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined.

Conclusion: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.
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http://dx.doi.org/10.1038/s41436-020-00993-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862064PMC
February 2021

HaNDL Syndrome: Case Report and Literature Review.

J Child Neurol 2019 03 5;34(3):161-167. Epub 2018 Dec 5.

1 Department of Pediatric Neurology, Massachusetts General Hospital, Boston, MA, USA.

Headache and Neurologic Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome is a rare stroke mimicker characterized by moderate to severe headache temporally associated with transient neurologic deficits, typically hemiparesis, hemisensory disturbance, and/or aphasia. Cerebrospinal fluid studies reveal a lymphocytosis and elevated protein. Episodes recur over a period no longer than 3 months. Here we describe the case of a 16-year-old boy who presented with 3 episodes of self-resolving neurologic deficits, papilledema on fundoscopic examination, and leptomeningeal enhancement on magnetic resonance imaging (MRI). We additionally review the 30 previously reported pediatric cases of HaNDL syndrome, with a focus on possible etiologic and pathophysiologic mechanisms of disease. The reported case and literature review highlight the benign episodic nature of this likely underrecognized syndrome as well as the higher than expected frequency of abnormal neuroimaging findings.
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http://dx.doi.org/10.1177/0883073818811546DOI Listing
March 2019

Focal Neurologic Deficits in a Febrile Adolescent.

Clin Pediatr (Phila) 2018 11 19;57(13):1597-1601. Epub 2018 Jul 19.

1 Massachusetts General Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1177/0009922818790048DOI Listing
November 2018

Authors' Response.

Pediatrics 2017 08;140(2)

Pediatric Emergency Medicine Physician.

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http://dx.doi.org/10.1542/peds.2017-1633BDOI Listing
August 2017

Wernicke Encephalopathy in Adolescents After Bariatric Surgery: Case Report and Review.

Pediatrics 2016 12 3;138(6). Epub 2016 Nov 3.

Division of Pediatric Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Roughly 1% of all weight loss surgery is performed in adolescents. There is strong evidence demonstrating significant postsurgical weight loss, improvement in quality of life, and reduction in comorbidities such as hypertension and diabetes. Reports of postoperative complications in adolescents are few because of the small sample size in most series. Despite vitamin supplementation, nutritional deficiencies requiring hospitalization occur occasionally after Roux-en-Y gastric bypass. Wernicke encephalopathy, a triad of ophthalmoplegia, ataxia, and altered mental status, is a serious consequence of thiamine (vitamin B) deficiency. Few cases of Wernicke encephalopathy after weight loss surgery have been reported in the literature and even fewer in the pediatric population. Here we describe a teenage girl who develops vomiting after Roux-en-Y gastric bypass and presented with nystagmus, irritability, and ataxia. The clinical presentation, diagnosis, and treatment of Wernicke encephalopathy in adolescents after bariatric surgery are discussed.
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http://dx.doi.org/10.1542/peds.2016-1039DOI Listing
December 2016

Child neurology: Exaggerated dermal melanocytosis in a hypotonic infant: a harbinger of GM1 gangliosidosis.

Neurology 2014 Oct;83(17):e166-8

From the Department of Neurology, Division of Child Neurology, Massachusetts General Hospital and Harvard Medical School, Boston.

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http://dx.doi.org/10.1212/WNL.0000000000000912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222851PMC
October 2014