Multisystemic smooth muscle dysfunction syndrome
| Multisystemic smooth muscle dysfunction syndrome | |
|---|---|
| Other names | Congenital mydriasis[1] |
Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a genetic disorder caused by R179 missense mutations in the ACTA2 gene. Initially described as a case report in 1999,[2] it was characterized in 2010[3] as a syndrome of congenital mydriasis, patent ductus arteriosus, and aneurysmal arterial disease—in particular aortic and thoracic aneurysms. 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.[4][5] 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), 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.[6]
References
- ↑ "Multisystemic smooth muscle dysfunction syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 25 September 2019.
- ↑ Adès, L. C.; Davies, R.; Haan, E. A.; Holman, K. J.; Watson, K. C.; Sreetharan, D.; Cao, S. N.; Milewicz, D. M.; Bateman, J. F. (October 1999). "Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent". Clinical Dysmorphology. 8 (4): 269–276. ISSN 0962-8827. PMID 10532176.
- ↑ Milewicz, Dianna M.; Østergaard, John R.; Ala-Kokko, Leena M.; Khan, Nadia; Grange, Dorothy K.; Mendoza-Londono, Roberto; Bradley, Timothy J.; Olney, Ann Haskins; Adès, Lesley; Maher, Joseph F.; Guo, Dongchuan; Buja, L. Maximilian; Kim, Dong; Hyland, James C.; Regalado, Ellen S. (23 August 2010). "De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction". American Journal of Medical Genetics Part A. 152A (10): 2437–2443. doi:10.1002/ajmg.a.33657. ISSN 1552-4825. PMC 3573757. PMID 20734336.
- ↑ Richer, J.; Milewicz, D.M.; Gow, R.; de Nanassy, J.; Maharajh, G.; Miller, E.; Oppenheimer, L.; Weiler, G.; O'Connor, M. (2 February 2012). "R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations". American Journal of Medical Genetics Part A. 158A (3): 664–668. doi:10.1002/ajmg.a.35206. ISSN 1552-4825. PMID 22302747.
- ↑ "Six-Month Old Infant with Familial ACTA2 R179H Mutation, Severe Pulmonary Hypertension, Pulmonary Interstitial Glycogenosis, Moderate-to-Severe Pulmonary Hypoplasia, and Prune Belly Sequence", American Thoracic Society International Conference Meetings Abstracts, C64. PEDIATRIC CASE REPORTS: BPD AND CONGENITAL LUNG DISEASES, American Thoracic Society, pp. A6074, May 2017
- ↑ Regalado, Ellen S; Mellor-Crummey, Lauren; De Backer, Julie; Braverman, Alan C; Ades, Lesley; Benedict, Susan; Bradley, Timothy J; Brickner, M Elizabeth; Chatfield, Kathryn C; Child, Anne; Feist, Cori; Holmes, Kathryn W; Iannucci, Glen; Lorenz, Birgit; Mark, Paul; Morisaki, Takayuki; Morisaki, Hiroko; Morris, Shaine A; Mitchell, Anna L; Ostergaard, John R; Richer, Julie; Sallee, Denver; Shalhub, Sherene; Tekin, Mustafa; Estrera, Anthony; Musolino, Patricia; Yetman, Anji; Pyeritz, Reed; Milewicz, Dianna M (4 January 2018). "Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations". Genetics in Medicine. 20 (10): 1206–1215. doi:10.1038/gim.2017.245. ISSN 1098-3600. PMC 6034999. PMID 29300374.