Smooth muscle disorders affecting both the intestine and the bladder have been known for a decade. However, the recent discovery of genes associated with these dysfunctions has led to the description of several clinical phenotypes. We performed a systematic review of all published cases involving seven genes with pathogenic variants, ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1, and included 28 articles describing 112 patients and 5 pregnancies terminated before birth. The most commonly described mutations involved ACTG2 (75/112, 67% of patients), MYH11 (14%) and FLNA (13%). Twenty-seven patients (28%) died at a median age of 14.5 months. Among the 76 patients for whom this information was available, 10 (13%) had isolated chronic intestinal pseudo-obstruction (CIPO), 17 (22%) had isolated megacystis, and 48 (63%) had combined CIPO and megacystis. The respective proportions of these phenotypes were 9%, 20% and 71% among the 56 patients with ACTG2 mutations, 20%, 20% and 60% among the 10 patients with MYH11 mutations and 50%, 50% and 0% among the 7 patients with FLNA mutations.

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.