Singleton-Merten syndrome (SMS) is a rare autosomal-dominant multisystem disorder characterized by early and extreme aortic and valvular calcification, dental anomalies (early-onset periodontitis and root resorption), osteopenia, and acro-osteolysis. A gain-of-function mutation in interferon induced with helicase C domain 1 (IFIH1), encoding melanoma differentiation-associated protein 5 (MDA5), causes SMS through dysregulation of the human innate immune response. DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD24 Syndromes with skeletal anomalies as a major feature
H01571 Singleton-Merten syndrome
Pathway-based classification of diseases [BR:br08402]
Immune system
nt06519 RLR signaling
H01571 Singleton-Merten syndrome
Rutsch F, MacDougall M, Lu C, Buers I, Mamaeva O, Nitschke Y, Rice GI, Erlandsen H, Kehl HG, Thiele H, Nurnberg P, Hohne W, Crow YJ, Feigenbaum A, Hennekam RC
Title
A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome.
Jang MA, Kim EK, Now H, Nguyen NT, Kim WJ, Yoo JY, Lee J, Jeong YM, Kim CH, Kim OH, Sohn S, Nam SH, Hong Y, Lee YS, Chang SA, Jang SY, Kim JW, Lee MS, Lim SY, Sung KS, Park KT, Kim BJ, Lee JH, Kim DK, Kee C, Ki CS
Title
Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome.
