ACTA2 leukovasculopathy: A rare pediatric white matter disorder

Sabo, Tonia; Stokes, Mathew; Karbhari, Nishika; Veltkamp, Daniel L.; Pfeifer, Cory M.

doi:10.1016/j.radcr.2020.05.031

Cited by 3 publications

(6 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, individuals with ACTA2 mutations present with both type A and type B aortic dissections and cardiovascular accidents, such as ischemic injuries (Hagan et al, 2000; Hao et al, 2006; Logeswaran et al, 2017). Other cardiological features of R179H variant are described in Table 1 (Amans et al, 2013; Ardhanari et al, 2020; Brodsky et al, 2014; Chen et al, 2019; D'Arco et al, 2018; Georgescu et al, 2015; Logeswaran et al, 2017; Milewicz et al, 2010; Moller et al, 2012; Moosa et al, 2013; Munot et al, 2012; Prabhu et al, 2017; Richer et al, 2012; Roulez et al, 2014; Rutledge et al, 2016; Sabo et al, 2020; She et al, 2021; Taubenslag et al, 2019; Yang et al, 2021; Yetman et al, 2015; Yeung et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Less frequent findings were cerebellar tonsillar ectopia, found in only one patient, encephalomalacia (2/8), Chiari I malformation (2/6) and hyppocampal abnormal gyration (1/4). Brain MRI features of R179H mutation patients are listed in Table 2 (Amans et al, 2013; Ardhanari et al, 2020; Brodsky et al, 2014; Chen et al, 2019; D'Arco et al, 2018; Georgescu et al, 2015; Logeswaran et al, 2017; Milewicz et al, 2010; Moller et al, 2012; Moosa et al, 2013; Munot et al, 2012; Prabhu et al, 2017; Richer et al, 2012; Roulez et al, 2014; Rutledge et al, 2016; Sabo et al, 2020; She et al, 2021; Taubenslag et al, 2019; Yang et al, 2021; Yetman et al, 2015; Yeung et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…A typical cerebrovascular pattern characterized by dilatation of proximal internal carotid artery and at the same time occlusive disease of terminal internal carotid artery, an abnormally straight course of intracranial arteries were described in MSMDS patients (Georgescu et al, 2015, Richer et al, 2012. Ardhanari et al, 2020;Brodsky et al, 2014;Chen et al, 2019;D'Arco et al, 2018;Georgescu et al, 2015;Logeswaran et al, 2017;Milewicz et al, 2010;Moller et al, 2012;Moosa et al, 2013;Munot et al, 2012;Prabhu et al, 2017;Richer et al, 2012;Roulez et al, 2014;Rutledge et al, 2016;Sabo et al, 2020;She et al, 2021;Taubenslag et al, 2019;Yang et al, 2021;Yetman et al, 2015;Yeung et al, 2017).…”

Section: Neurological and Neuroradiological Featuresmentioning

confidence: 96%

“…In association to the cardiac features at 38 weeks of pregnancy, an ultrasound scan detected in our patient an enlarged bladder. According to literature review, the most common genitourinary anomalies in patients with R179H ACTA2 mutation were hypocontractile bladder and hydronephrosis, rarely prune-belly syndrome (Table 1) (Amans et al, 2013, Ardhanari et al, 2020, Brodsky et al, 2014, Chen et al, 2019, D'Arco et al, 2018, Georgescu et al, 2015, Logeswaran et al, 2017, Milewicz et al, 2010, Moller et al, 2012, Moosa et al, 2013, Munot et al, 2012, Prabhu et al, 2017, Richer et al, 2012, Roulez et al, 2014, Rutledge et al, 2016, Sabo et al, 2020, She et al, 2021, Taubenslag et al, 2019, Yang et al, 2021, Yetman et al, 2015, Yeung et al, 2017.…”

Section: Gastrointestinal and Genitourinary Featuresmentioning

confidence: 99%

See 3 more Smart Citations

Neonatal diagnosis of ACTA2‐related disease: A case report and review of literature

Lupo

Gregorio

Mastrogiorgio

et al. 2023

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Multisystemic smooth muscle dysfunction syndrome (MSMDS, OMIM # 613834) is a rare autosomal dominant condition caused by pathogenetic variants of ACTA2 gene that result in impaired muscle contraction. MSMDS is characterized by an increased susceptibility to aneurismal dilatations and dissections, patent ductus arteriosus, early onset coronary artery disease, congenital mydriasis, chronic interstitial lung disease, hypoperistalsis, hydrops of gall bladder, and hypotonic bladder. Here, we report an early diagnosis of a MSMDS related to ACTA2 p.Arg179His (R179H) mutation in a newborn and performed a review of the literature. An early diagnosis of MSMDS is extremely important, because of the severe involvement of cardiovascular system in the MSMDS. Multidisciplinary care and surveillance and timely management of symptoms are important to reduce the risk of complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Neurological and Neuroradiological Featuresmentioning

confidence: 96%

Section: Gastrointestinal and Genitourinary Featuresmentioning

confidence: 99%

See 2 more Smart Citations

Neonatal diagnosis of ACTA2‐related disease: A case report and review of literature

Lupo

Gregorio

Mastrogiorgio

et al. 2023

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Numerous features, such as aortic and cerebrovascular disease, mydriasis, underactive bladder and intestine, pulmonary hypertension, and brain white matter anomalies were associated with this syndrome [42]. According to published data, almost 80% of patients had proximal internal carotid artery stenosis and neurological manifestations were reported, including developmental delay and learning difficulties (19% and 7%, respectively), seizures (18%), but also hemiparesis (16%) and spasticity of the lower (6%) and upper (3%) extremities [43,44]. Abnormal brain development, a noticeable characteristic in Arg179Cys mutation carriers, highlights the role of alpha-2 actin these processes [45].…”

Section: Autosomal Dominant Inheritancementioning

confidence: 99%

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

Janković

Petrović²,

Novaković

et al. 2022

IJMS

View full text Add to dashboard Cite

Strokes within pediatric populations are considered to be the 10th leading cause of death in the United States of America, with over half of such events occurring in children younger than one year of life. The multifactorial etiopathology that has an influence on stroke development and occurrence signify the importance of the timely recognition of both modifiable and non-modifiable factors for adequate diagnostic and treatment approaches. The early recognition of a stroke and stroke risk in children has the potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after the onset of a stroke, improving the outcomes and quality of life for affected children and their families. The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of single-gene disorders. In this review, the most significant single gene disorders associated with pediatric stroke are presented, along with specific therapeutic options whenever they exist. Besides monogenic disorders that may present with stroke as a first symptom, genetic polymorphisms may contribute to the risk of pediatric and perinatal stroke. The most frequently studied genetic risk factors are several common polymorphisms in genes associated with thrombophilia; these genes code for proteins that are part of the coagulation cascade, fibrolysis, homocystein metabolism, lipid metabolism, or platelets. Single polymorphism frequencies may not be sufficient to completely explain the stroke causality and an analysis of several genotype combinations is a more promising approach. The recent steps forward in our understanding of the disorders underlying strokes has given us a next generation of therapeutics and therapeutic targets by which to improve stroke survival, protect or rebuild neuronal connections in the brain, and enhance neural function. Advances in DNA sequencing and the development of new tools to correct human gene mutations have brought genetic analysis and gene therapy into the focus of investigations for new therapeutic options for stroke patients.

show abstract

Clinical Approach to Genetic Cerebral Arteriopathy in the Adult Patient With Ischemic Stroke

Haddad,

Kumar,

Shearn-Nance

et al. 2024

Neurol Genet

View full text Add to dashboard Cite

Genetic arteriopathies leading to stroke in adults constitute a diverse group of cerebrovascular disorders with distinct etiologies, pathophysiologic mechanisms, and clinical presentations. As imaging modalities better delineate subtle changes in cerebral vasculature and access to genetic testing increases, the detection rate for these conditions is expected to rise, particularly among young adults with idiopathic cerebral arteriopathy and stroke. Adults with stroke in the setting of a genetic cerebral arteriopathy often present with few traditional stroke risk factors and, in certain cases, have characteristic clinical features, cerebrovascular imaging findings, and often concurrent systemic vasculopathy, such as aortopathy, which are important to recognize. Given that there are over 50 recognized genetic cerebral arteriopathies that can cause ischemic and hemorrhagic stroke in young adults, it can be a significant diagnostic challenge for the practicing neurologist when faced with a genetic cerebral arteriopathy, because clinical algorithms for a systematic approach to genetic cerebral arteriopathies are lacking. In this review, we present a phenotype-driven, clinically oriented algorithm to guide the diagnostic workup when suspecting a genetic cerebral arteriopathy in an adult patient while highlighting the genetic basis of each disease, molecular mechanisms, clinical manifestations, diagnostic approaches, and emerging therapeutic strategies. Moreover, given the lack of widely available gene panels for diagnostic germline testing for genetic cerebral arteriopathies, we propose key genes to be tested and focused on in each clinical scenario, to better decipher the underlying diagnosis in these rare conditions.

show abstract

ACTA2 leukovasculopathy: A rare pediatric white matter disorder

Cited by 3 publications

References 8 publications

Neonatal diagnosis of ACTA2‐related disease: A case report and review of literature

Neonatal diagnosis of ACTA2‐related disease: A case report and review of literature

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

Clinical Approach to Genetic Cerebral Arteriopathy in the Adult Patient With Ischemic Stroke

Contact Info

Product

Resources

About