Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS) affects fewer than 100 people worldwide, and its symptoms vary widely from one patient to another. Because it involves multiple organs and systems, early signs are often misdiagnosed or only partially recognized.
From congenital mydriasis to cardiovascular, neurological, or digestive complications, many symptoms resemble more common conditions, delaying diagnosis and increasing risk.
This page does not replace medical advice. Always consult your healthcare team.
Symptoms differ between patients, but the most characteristic include:
Congenital mydriasis (fixed and dilated pupils): often the first visible sign, frequently accompanied by tortuous retinal vessels
Congenital heart defects (Patent Ductus Arteriosus (PDA) or Aortopulmonary Window (APW))
Brain white matter abnormalities
Aortic coarctation
PDA repair needed
Aortopulmonary window
White matter abnormalities are usually present
When two of these three signs are present, genetic testing for ACTA2 mutations should be strongly considered.
These hallmark signs often appear early in life, sometimes even at birth, and are critical for early recognition.
MSMDS symptoms vary between individuals, but the most characteristic include:
Seizures may occur due to ischemic brain injury or abnormal blood flow regulation
Often associated with scalloped iris margin and tortuous retinal vessels
These conditions may require early surgical intervention and lifelong monitoring.
Pulmonary complications can range from mild respiratory symptoms to severe disease requiring close follow-up.
Patients often report difficulty regulating body temperature and may not experience normal “chills”.
Symptoms range from mild feeding difficulties to life-threatening bowel obstruction.
Prune‑Belly Syndrome (PBS): genetic testing is recommended when PBS appears without mechanical obstruction and coexists with PDA
MSMDS affects smooth muscle cells throughout the body. Because these cells are present in blood vessels, lungs, digestive system, and bladder, the disease can impact multiple organs simultaneously, although its symptoms are frequently treated as separate conditions:
Individually, these symptoms may seem unrelated, but this fragmentation can delay diagnosis for years. Recognizing them together is essential for suspecting MSMDS and initiating genetic testing.
MSMDS is a complex puzzle, but not an impossible one.
Each symptom alone may be confusing, but together, they form the map that leads to a timely and accurate diagnosis.
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https://www.neurology.org/doi/abs/10.1212/WNL.0000000000206311
2. Tonia M. Sabo, Mathew A. Stokes, Nishika Karbhari, Daniel L. Veltkamp, Cory M. Pfeifer,
ACTA2 leukovasculopathy: A rare pediatric white matter disorder,
Radiology Case Reports,2020 https://www.sciencedirect.com/science/article/pii/S193004332030203X
3. Catherine Wing Yan Tam, MB, BCh, BAO, MSc, FRCR • King Kenneth Cheung, MBBS, BSc, PhD, FRCR. Case 319: Multisystemic Smooth Muscle DysfunctionSyndrome. Radiology 2023 309:2
https://pubs.rsna.org/doi/epdf/10.1148/radiol.222049
4. Logeswaran, T. et al.Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome. Am. J. Med. Genet. A 173, 959–965 (2017). https://pubmed.ncbi.nlm.nih.gov/28328125/
5. Tonia M. Sabo, Mathew A. Stokes, Nishika Karbhari, Daniel L. Veltkamp, Cory M. Pfeifer,
ACTA2 leukovasculopathy: A rare pediatric white matter disorder, Radiology Case Reports,
Volume 15, Issue 8, 2020. https://www.sciencedirect.com/science/article/pii/S193004332030203X
6. Micke K. C., Stence N. V., Meyers M. L., Chatfield K. C., Vemulakonda V. M. (2023).Megacystis associated with an underlying ACTA2 variant and diagnosis of multisystemic smooth muscle dysfunction syndrome: a case report. Urology, 2022 https://pubmed.ncbi.nlm.nih.gov/36495950/
7. J Richer 1, D M Milewicz, R Gow, J de Nanassy, G Maharajh, E Miller, L Oppenheimer, G Weiler, M O’Connor, R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations Am J Med Genet A. 2012
https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.a.35206
8. Li Q, Cui L, Su J and Shen Y (2025) Case report: Multisystemic smooth muscle dysfunction syndrome: a rare genetic cause of infantile interstitial lung disease Front. Pharmacol. 15:1510969. doi: 10.3389/fphar.2024.1510969
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1510969/full
*This content is not intended as a substitute for professional medical advice, diagnosis, or treatment. Should you require medical advice, please contact a qualified medical professional who is familiar with Multisystemic Smooth Muscle Dysfunction Syndrome.
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