Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a genetic disorder caused by R179

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Missense mutations change amino acids, which in turn alt ...

s in the

ACTA2 ACTA2 (actin alpha 2) is an actin protein with several aliases including alpha-actin, alpha-actin-2, aortic smooth muscle or alpha smooth muscle actin (α-SMA, SMactin, alpha-SM-actin, ASMA). Actins are a family of globular multi-functional pr ...

gene. Initially described as a case report in 1999, it was characterized in 2010 as a syndrome of congenital

mydriasis Mydriasis is the Pupillary dilation, dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, Physical trauma, trauma, or the use of c ...

patent ductus arteriosus Patent ductus arteriosus (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after childbirth, birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs from the aorta, which has a h ...

, and aneurysmal arterial disease—in particular aortic and thoracic

aneurysm An aneurysm is an outward :wikt:bulge, bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also b ...

s. The disorder has variable penetrance, ranging from severely symptomatic and fatal in early neonatal period to a more benign and manageable course with surgical intervention.

Signs and symptoms

Signs and symptoms are usually detectable prenatally or shortly after birth. In its severe manifestations, MSMDS has been associated with prune belly sequence. In less severe forms, the earliest signs of MSMDS are congenital fixed mydriasis (can be misdiagnosed as partial

aniridia Aniridia is a condition characterized by the absence or near absence of the iris, the colored, muscular ring in the eye that controls the size of the pupil and regulates the amount of light entering the eye. This absence results in a primarily b ...

), and a PDA requiring surgical intervention. Most carriers of the mutation will eventually develop thoracic arterial disease between the ages of 10–25.

Pathogenesis

The most commonly associated mutation with MSMDS is R179H.

Management

Management of MSMDS requires lifelong surveillance and surgical intervention when required. The first comprehensive guidelines were published in 2018 by the same group that first categorized the syndrome in 2010.

References

Rare genetic syndromes {{Genetic-disorder-stub