ACTA2 mutation is responsible for multisystemic smooth muscle dysfunction syndrome with seizures: A case report and review of literature

Abstract

BACKGROUND ACTA2 gene is a specific gene that encodes actin α2. Multisystem smooth muscle dysfunction syndrome (MSMDS) is a multisystem disease characterized by aortic and cerebrovascular lesions caused by ACTA2 gene mutations. There have been many reports of cardiac, pulmonary and cerebrovascular lesions caused by MSMDS; however, few studies have focused on seizures caused by MSMDS. CASE SUMMARY Our patient was a girl aged 7 years and 8 mo with recurrent cough, asthma and seizures for 7 years. She was diagnosed with severe pneumonia, congenital heart disease, cardiac insufficiency, and malnutrition in the local hospital. Cardiac ultrasonography revealed congenital heart disease, patent ductus arteriosus (with a diameter of 0.68 cm), left coronary arteriectasis, patent oval foramen (0.12 cm), tricuspid and pulmonary regurgitation, and pulmonary hypertension. Cerebral magnetic resonance imaging and magnetic resonance angiography indicated stiffness in the brain vessels, together with multiple aberrant signaling shadows in bilateral paraventricular regions. A heterozygous mutation ( c.536 G>A) was identified in the ACTA2 gene, resulting in generation of p.R179H. Finally, the girl was diagnosed with MSMDS combined with epilepsy. The patient had 4 episodes of seizures before treatment, and no onset of seizure was reported after oral administration of sodium valproate for 1 year. CONCLUSION MSMDS has a variety of clinical manifestations and unique cranial imaging features. Cerebrovascular injury and white matter injury may lead to seizures. Gene detection can confirm the diagnosis and prevent missed diagnosis or misdiagnosis.

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

“…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).…”

“…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).…”

“… Note : a : Milewicz et al (2010); b : Ardhanari et al (2020); c : Munot et al (2012); d : Richer et al (2012); e : Roulez et al (2014); f : Yetman et al (2015); g : Logeswaran et al (2017); h : Moller et al (2012); i : Moosa et al (2013); j : Amans et al (2013); k : Brodsky et al (2014); l : Georgescu et al (2015); m : Yeung et al (2017); n : Rutledge et al (2016); o : Prabhu et al (2017); p : D'Arco et al (2018); q : Taubenslag et al (2019); r : Chen et al (2019), s : Sabo et al (2020); t : She et al (2021); u : Yang et al (2021). …”

“…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).…”

“…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.…”