scholarly journals Two Cases of Leigh Syndrome in One Family: Diagnostic Challenges and Clinical Management Experience in Latvia

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Arta Katkevica ◽  
Madara Kreile ◽  
Ieva Grinfelde ◽  
Gita Taurina ◽  
Ieva Micule ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Clinical Management ◽  
Clinical Presentation ◽  
Neurodegenerative Disorder ◽  
Leigh Syndrome ◽  
Live Births ◽  
Pathogenic Variants ◽  
Associated Symptoms ◽  
Management Experience ◽  
Common Infections

Leigh syndrome is a neurodegenerative disorder with an incidence of 1 : 40,000 live births. The clinical presentation of LS is highly variable with heterogeneity in the disease-associated symptoms of cerebellar, motor, and extrapyramidal dysfunction and common infections. There is no effective treatment for this condition; as such, the prognosis of this condition is very poor with death occurring within the first few years of life. In this study, we report the first LS case in Latvia with SURF1 pathogenic variants in two siblings. The difficulties encountered establishing a diagnosis for the first proband and the effective prenatal diagnosis for the second offspring that led to termination of the pregnancy are discussed.

scholarly journals Term Neonate Presenting with the Combined Occurrence of Mucolipidosis Type II and Leigh Syndrome

2019 ◽  
Vol 09 (02) ◽  
pp. 137-141
Author(s):  
Rebecca R. Speer ◽  
Uzoamaka C. Ezeanya ◽  
Sarah J. Beaudoin ◽  
Kristen M. Glass ◽  
Christiana N. Oji-Mmuo
Keyword(s):  
Autosomal Recessive ◽  
Clinical Presentation ◽  
Autosomal Recessive Disease ◽  
Neurodegenerative Disorder ◽  
Leigh Syndrome ◽  
Genetic Alterations ◽  
Chromosome 12 ◽  
Type Ii ◽  
Mucolipidosis Ii ◽  
Mucolipidosis Type

AbstractMucolipidosis II α/beta (MLII) is an autosomal recessive disease in which a gene mutation leads to improper targeting of lysosomal enzymes with an end result of accumulation of lysosomes in the mitochondria resulting in a dysfunctional mitochondria.1 Leigh syndrome (LS) is a rare progressive neurodegenerative disorder associated with dysfunctional mitochondria and oxidative phosphorylation.4 Both disease processes typically present in infancy.3 7 Herein, we present a case of an infant diagnosed with both mucolipidosis II and Leigh syndrome. Genetic analysis in this case revealed two mutations (NDUFA12 c.178C > T p.Arg60* and GNPTAB c.732_733delAA) on the long arm of chromosome 12 as the etiology of MLII and LS in this neonate, respectively. We are unaware of any previously published cases of the presence of these two diseases occurring in the same patient. The complex clinical presentation of this case led to a delay in the diagnosis, and we believe that the clinical phenotypes of these two conditions were likely worsened. The genetic alterations presented in this case occurred as a result of mutations on chromosome 12. We suggest further investigation into the potential overlap in the pathophysiology, specifically the inheritance pattern, linkage disequilibrium, mitochondrial–lysosomal interaction, or crosstalk contributing to both diseases.

scholarly journals A novel de novo DDX3X missense variant in a female with brachycephaly and intellectual disability: a case report

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Giada Moresco ◽  
Jole Costanza ◽  
Carlo Santaniello ◽  
Ornella Rondinone ◽  
Federico Grilli ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Clinical Presentation ◽  
De Novo ◽  
Clinical Signs ◽  
Missense Variant ◽  
Psychomotor Development ◽  
Helicase Domain ◽  
Protein Activity ◽  
Mrna Metabolism ◽  
Pathogenic Variants

Abstract Background De novo pathogenic variants in the DDX3X gene are reported to account for 1–3% of unexplained intellectual disability (ID) in females, leading to the rare disease known as DDX3X syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs. Case presentation We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the DDX3X gene (c.625C > G) by whole exome sequencing (WES). The DDX3X gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense DDX3X mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female DDX3X patients, and macroglossia, that has never been associated with the syndrome. Conclusions This case expands the knowledge of DDX3X pathogenic variants and the associated DDX3X syndrome phenotypic spectrum.

scholarly journals Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report

2021 ◽  
Vol 7 (2) ◽  
pp. 28
Author(s):  
Camille S. Corre ◽  
Dietrich Matern ◽  
Joan E. Pellegrino ◽  
Carlos A. Saavedra-Matiz ◽  
Joseph J. Orsini ◽  
...  
Keyword(s):  
New York ◽  
Enzyme Activity ◽  
Clinical Presentation ◽  
Neurodegenerative Disorder ◽  
New York State ◽  
Disease Onset ◽  
Early Infancy ◽  
Krabbe Disease ◽  
Activity Levels ◽  
Hematopoietic Stem

Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification and risk-stratification of patients based on laboratory values to predict disease onset in early infancy or later in life. The biomarker psychosine plays a key role in NBS algorithms to ascertain probability of early-onset disease. This report describes a patient who was screened positive for KD in New York State, had a likely pathogenic genotype, and showed markedly reduced enzyme activity but surprisingly low psychosine levels. The patient ultimately developed KD in late infancy, an outcome not clearly predicted by existing NBS algorithms. It remains critical that psychosine levels be evaluated alongside genotype, enzyme activity levels, and the patient’s evolving clinical presentation, ideally in consultation with experts in KD, in order to guide diagnosis and plans for monitoring.

scholarly journals A Broader Perspective on the Prenatal Diagnosis of Cornelia de Lange Syndrome: Review of the Literature and Case Presentation

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 142
Author(s):  
Anca Maria Panaitescu ◽  
Simona Duta ◽  
Nicolae Gica ◽  
Radu Botezatu ◽  
Florina Nedelea ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Cornelia De Lange Syndrome ◽  
Facial Features ◽  
Genetic Condition ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Limb Reduction ◽  
Ultrasound Findings ◽  
Prenatal Management ◽  
Cornelia De Lange

Cornelia de Lange syndrome (CDLS) is caused by pathogenic variants in genes which are structural or regulatory components of the cohesin complex. The classical Cornelia de Lange (CDLS) phenotype is characterized by distinctive facial features, growth retardation, upper limb reduction defects, hirsutism, and developmental delay. Non-classical phenotypes make this condition heterogeneous. Although CDLS is a heterogeneous clinical and genetic condition, clear diagnostic criteria have been described by specialist consensus. Many of these criteria refer to features that can be seen on prenatal ultrasound. The aim of this paper is twofold: to present the ultrasound findings in fetuses affected by CDLS syndrome; to discuss the recent advances and the limitations in the ultrasound and genetic prenatal diagnosis of CDLS. Our review aims to offer, apart from the data needed to understand the genetics and the prenatal presentation of the disease, a joint perspective of the two specialists involved in the prenatal management of this pathology: the fetal medicine specialist and the geneticist. To better illustrate the data presented, we also include a representative clinical case.

scholarly journals P02.49: Prenatal diagnosis and clinical management of the body stalk anomaly during gestation. The importance of the precocious diagnostic

2006 ◽  
Vol 28 (4) ◽  
pp. 534-534
Author(s):  
E. Cordioli ◽  
L. C. S. Bussamra ◽  
G. Lobo ◽  
C. A. Souza ◽  
W. J. Hisaba ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Clinical Management ◽  
The Body

Un’opprimente tumefazione laterocervicale... da far mancare il respiro

2021 ◽  
Vol 40 (1) ◽  
pp. 15-18
Author(s):  
Chiara Mellino ◽  
Pietro Gasperini ◽  
Maria Luisa Conte ◽  
Valeria Dell’Omo ◽  
Francesca Libertucci ◽  
...  
Keyword(s):  
Early Childhood ◽  
Lymphatic System ◽  
Clinical Presentation ◽  
Hormone Level ◽  
Male Infant ◽  
Low Flow ◽  
Lymphatic Malformations ◽  
Live Births ◽  
Adjacent Structures ◽  
Life Threatening

Lymphatic malformations are low-flow vascular anomalies of the lymphatic system that occur in one out of 2-4,000 live births. They may be classified as macrocystic (diameter > 1 cm), microcystic (diameter < 1 cm) or mixed. Lymphatic malformations that are not prenatally diagnosed are typically diagnosed at birth or in early childhood. The clinical presentation can be quite variable, ranging from a focal area with minimal swelling to large involvement with compromise of adjacent structures. Up to 75% of lymphatic malformations are found in the cervicofacial region and their presence in the aerodigestive tract can lead to life-threatening airway obstruction. Lesions can grow slowly or rapidly and suddenly due to infection, trauma, bleeding or hormone level changes. The paper describes the case of a 9-month-old male infant with cervical macrocystic lymphangioma appeared during a febrile airway infection and misdiagnosed with bacterial lymphadenitis.

scholarly journals Compound heterozygous PLA2G6 loss-of-function variants in Swaledale sheep with neuroaxonal dystrophy

2020 ◽  
Author(s):  
Anna Letko ◽  
Ben Strugnell ◽  
Irene M. Häfliger ◽  
Julia M. Paris ◽  
Katie Waine ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Neuronal Degeneration ◽  
Neuroaxonal Dystrophy ◽  
Histopathological Analysis ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Genome Region ◽  
Pathogenic Variants ◽  
Progressive Ataxia ◽  
Intron 2

Abstract Sporadic occurrences of neurodegenerative disorders including neuroaxonal dystrophy (NAD) have been previously reported in sheep. However, so far no causative genetic variant has been found for ovine NAD. The aim of this study was to characterize the phenotype and the genetic aetiology of an early-onset neurodegenerative disorder observed in several lambs of purebred Swaledale sheep, a native English breed. Affected lambs showed progressive ataxia and stiff gait and subsequent histopathological analysis revealed the widespread presence of axonal spheroid indicating neuronal degeneration. Thus, the observed clinical phenotype could be explained by a novel form of NAD. After SNP genotyping and subsequent linkage mapping within a paternal half-sib pedigree with a total of five NAD-affected lambs, we identified two loss-of-function variants by whole-genome sequencing in the ovine PLA2G6 gene situated in a NAD-linked genome region on chromosome 3. All cases were carriers of a compound heterozygous splice site variant in intron 2 and a nonsense variant in exon 8. Herein we present evidence for the occurrence of a familial novel form of recessively inherited NAD in sheep due to allelic heterogeneity at PLA2G6. This study reports two pathogenic variants in PLA2G6 causing a novel form of NAD in Swaledale sheep which enables selection against this fatal disorder.

scholarly journals Fucosidosis—Clinical Manifestation, Long-Term Outcomes, and Genetic Profile—Review and Case Series

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1383 ◽  
Author(s):  
Karolina M. Stepien ◽  
Elżbieta Ciara ◽  
Aleksandra Jezela-Stanek
Keyword(s):  
Neurodegenerative Disorder ◽  
Respiratory Infections ◽  
Clinical Manifestations ◽  
Case Series ◽  
Genetic Profile ◽  
Nonsense Mutations ◽  
Pathogenic Variants ◽  
One Stop ◽  
Stop Loss

Fucosidosis is a neurodegenerative disorder which progresses inexorably. Clinical features include coarse facial features, growth retardation, recurrent upper respiratory infections, dysostosis multiplex, and angiokeratoma corporis diffusum. Fucosidosis is caused by mutations in the FUCA1 gene resulting in α-L-fucosidase deficiency. Only 36 pathogenic variants in the FUCA1 gene are related to fucosidosis. Most of them are missense/nonsense substitutions; six missense and 11 nonsense mutations. Among deletions there were eight small and five gross changes. So far, only three splice site variants have been described—one small deletion, one complete deletion and one stop-loss mutation. The disease has a significant clinical variability, the cause of which is not well understood. The genotype–phenotype correlation has not been well defined. This review describes the genetic profile and clinical manifestations of fucosidosis in pediatric and adult cases.

HIV Infection

2017 ◽  
Author(s):  
Meena Kannan ◽  
Harrison Taylor ◽  
William Tyor
Keyword(s):  
Nervous System ◽  
Differential Diagnosis ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Clinical Management ◽  
Cytomegalovirus Infection ◽  
Clinical Presentation ◽  
Opportunistic Infections ◽  
Cryptococcal Infection ◽  
Combined Antiretroviral Therapy

This chapter focuses on four common opportunistic infections of the nervous system associated with HIV infection, namely cryptococcal infection, cytomegalovirus infection, progressive multifocal leukoencephalitis, and toxoplasmosis. Essential features of neurobiology, clinical presentation, differential diagnosis, diagnostic workup, clinical management, and outcome are discussed for each condition. Although combined antiretroviral therapy for HIV has generally reduced the incidence of these complications of HIV infection, they remain important considerations, especially in areas in which antiretrovirals are unavailable or have limited availability.

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