Hereditary connective tissue disease is known to cause aortic lesions at an early age. Familial aortic aneurysm/dissection is caused due to an ACTA2 mutation that affects smooth muscle structure. We present a case of a 15-year-old boy with a mild developmental disorder in whom no abnormalities were identified on previous physical examinations. The patient presented with severe left heart failure, extensive dissection from the ascending aorta to the common iliac artery, and myocardial and cerebral infarctions. He underwent an urgent Bentall surgery. Six months later, the patient underwent surgical reconstruction of the abdominal aorta from the aortic arch and returned to normal daily activities. Pathological examination demonstrated the absence of elastic fibers but presence of abundant reticular fibers and mucopolysaccharides from the tunica intima to the media. Genetic testing revealed a heterozygous missense variant of the ACTA2 gene. To the best of our knowledge, this is the first sporadic case of structurally abnormal smooth muscle organization resulting in clinical symptoms with no previously reported pathogenicity.

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.

Mutations in ACTA2 gene can lead to multisystemic smooth muscle dysfunction, including cerebrovascular disease. Treatment strategies for this rare entity remain controversial, and patients are at increasing risk of neurological sequelae. We herein present the case of an 11-year-old boy previously diagnosed with an ACTA2 gene mutation who developed repetitive transient ischemic attacks and treated with bosentan, an oral endothelin receptor antagonist. Magnetic resonance imaging revealed bilateral, periventricular white matter T2 hyperintensities, and magnetic resonance angiography identified several abnormalities including fusiform dilatation in the proximal segments of internal cerebral arteries, together with followed by terminal segmental stenosis. The distal branches showed a markedly straightened course with no increase in lenticulostriate collaterals. Magnetic resonance imaging also revealed an increase in the number and size of large periventricular white matter lesions located in the left frontal lobe with the progression of ischemic symptoms. Instead of revascularization surgery, the administration of bosentan was started due to the high risk of perioperative ischemic sequelae. After bosentan initiation, the patient\'s repetitive episodes of cerebral ischemia ceased, and there has been no increase in the number of white matter lesions for 7 years. Bosentan might be beneficial for treating cerebral ischemia associated with ACTA2 cerebral arteriopathy by maintaining the dilatation of stenotic vessels and adequate systemic blood flow and should be considered before performing revascularization surgery.

The MYH11 gene codes for smooth muscle myosin heavy chain, which has a critical function in maintaining vascular wall stability. Patients with this mutation most commonly have aortic and cardiac defects. Documented involvement of intracranial vessels is exceptional.
A 29-year-old woman with a history of patent ductus arteriosus and aortic dissection was found to have incidental bilateral stenosis of the terminal internal carotid arteries as well as the proximal anterior cerebral arteries, middle cerebral arteries, and posterior cerebral arteries on magnetic resonance angiography that was obtained for unrelated symptoms. There was no evidence of basal collateral formation, and a generalized straightening of the vessels was observed. These angiographic findings have been typically observed in patients with ACTA2 mutations. Thus, genetic testing was pursued, which uncovered the presence of an MYH11 mutation. Follow-up imaging at 51 months demonstrated that the intracranial stenosis remained stable without evidence of basal collateral formation. She did not experience any neurologic events during the follow-up interval.
Intracranial vessel involvement in patients with MYH11 mutations is rare. Vigilant cerebrovascular monitoring should be practiced in this population to guide appropriate management. Reporting of similar cases is important to improve understanding of the development of idiopathic intracranial stenosis in young individuals.

Thoracic aortic aneurysm (TAA) and/or thoracic aortic aneurysm and dissection (TAAD) is characterized by a considerable risk of morbidity and mortality of affected individuals. It is inherited in an autosomal dominant pattern and the 20% of patients with non-syndromic TAA have a positive family history. To date, the genetic basis of Cypriot patients with TAA has not been investigated. The purpose of this case report is to determine underlying genetic cause in this Cypriot family with TAA.
In this report we present a patient with hyper-acute onset chest and back pain diagnosed with Type A Aortic Dissection with severe aortic valve regurgitation, who underwent emergency aortic surgery and Bentall procedure. Further investigation of the patient\'s family was undertaken where both parents and an additional child were also found to be affected. A targeted sequencing panel including genes with known association to TAA was used to identify causative mutations in the index patient. Massively Parallel Sequencing results identified a frameshift deletion c.363_367del GAGTC, p.Met121Ilefs*5 in the ACTA2 gene and a non-synonymous variant c.3234C > G, p.Ile1078Met in the MYH11 gene. The presence or absence of these variants in the index patient and other family members was verified by Sanger sequencing. To our knowledge, this is the first report of a Cypriot family case diagnosed with TAA presented by two novel variants one in the ACTA2 and the other in the MYH11 genes.
We describe two novel variants in a Cypriot family with TAA that are potentially pathogenic, highlighting the importance of molecular genetic evaluation in families with TAA. These results may prove useful for screening purposes in Cypriot patients with non-syndromic familial TAA facilitating early identification of atrisk family members and direct intervention.

Mutations in the smooth muscle-specific isoform of alpha actin (ACTA2) cause smooth muscle dysfunction in arteries. This rare loss-of-function mutation may cause a diffuse occlusive cerebral arteriopathy, resulting in stroke. While ACTA2 arteriopathy is often described as moyamoya-like, it has a distinct phenotype characterized by dilation of the proximal internal carotid artery (ICA) and occlusion of the terminal ICA and proximal middle cerebral artery. Intracranial arteries have an abnormally straight course, often with small aneurysms. There is limited experience with revascularization procedures for ACTA2 arteriopathy, and the safety and efficacy of these procedures are unknown. In this paper the authors present a symptomatic 6-year-old patient with ACTA2 cerebral arteriopathy who underwent both indirect revascularization and direct cerebrovascular bypass. Postoperatively, the patient suffered an ischemic infarct in a neighboring vascular territory. While direct cerebrovascular bypass is technically feasible, patients with ACTA2 arteriopathy may be at increased risk for perioperative stroke compared with patients with moyamoya disease.