Singleton–Merten syndrome: An autosomal dominant disorder with variable expression

Abstract

In 1973, Singleton and Merten described two females with abnormal dentition, unique radiographic changes especially of the hands, and severe calcification and intimal weakening of the aortic arch and valve. Since then three additional cases with similar features have been reported and the diagnosis was suggested in another three individuals. We present an update of one case and the detailed clinical phenotype of six other cases with Singleton-Merten syndrome. The occurrence of the disorder in six members of two families and vertical male-to-male transmission indicate an autosomal dominant pattern of inheritance. Variability in phenotype, also within a single family, is significant. Core manifestations are marked aortic calcification, dental anomalies (delayed eruption and immature root formation of primarily the anterior permanent teeth, and early loss of permanent teeth due to short roots, acute root resorption, high caries, and aggressive alveolar bone loss), osteopenia and acro-osteolysis, and to a lesser extend also glaucoma, psoriasis, muscle weakness, and joint laxity. Additional clinical characteristics described here include particular facial characteristics (high anterior hairline, broad forehead, smooth philtrum, thin upper vermillion) and abnormal joint and muscle ligaments. The cause and pathogenesis of this syndrome remain unknown. © 2013 Wiley Periodicals, Inc.

Mutations in DDX58, which Encodes RIG-I, Cause Atypical Singleton-Merten Syndrome

“…1 Since then, a few SMS-affected families have been described, and joint laxity, muscle weakness, and psoriasis were often reported in individuals with SMS. [1][2][3][4] One of the main characteristics of classic SMS is the presence of dental anomalies, including delayed exfoliation or eruption of the primary teeth and early loss of permanent teeth. 1,2 Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown.…”

“…[1][2][3][4] One of the main characteristics of classic SMS is the presence of dental anomalies, including delayed exfoliation or eruption of the primary teeth and early loss of permanent teeth. 1,2 Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. 2 DDX58, also known as retinoic-acid-inducible gene I (RIG-I), is a 925-residue cytoplasmic viral RNA receptor and a member of the RIG-I-like receptor (RLR) family, which also includes IFIH1 and DHX58.…”

Prosthetic rehabilitation in a patient with Singleton Merten syndrome and acrylic resin hypersensitivity

“…Singleton Merten syndrome (SMS) is an autosomal dominant genetic disorder with variable expression and symptoms present during childhood [4,5,13,17]; the pathophysiology is unknown because of the rarity of this disease [5,12,16]. SMS major features are extensive aortic calcifications, dental anomalies due to the phenotype of dental dysplasia, abnormal ossifications, psoriasis, and glaucoma [12].…”

“…Clinically, individuals with SMS show with fever of unknown origin, muscle weakness, impaired motor development, abnormal dentition, glaucoma, photosensitivity, heart block, deformities of the feet and hands, skin lesions, and chronic psoriasis [2,5,16]. Radiological aspects include skeletal demineralization, expanded shafts of metacarpal and phalanges with extended medullary sinuses, cardiomegaly, and proximal aortic intramural calcification, with occasional extension to the mitral or aortic valve [2,16,19].…”

“…Based on dental development, the main features are developmental anomalies observed as late exfoliation of molars; late eruption of premolars; formation of truncated or missing roots in incisors, canines, and molars; and abnormal alveolus with extensive area of bone resorption [5].…”