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Singleton-Merten Syndrome 2

OMIM ID:

autosomal dominant

Singleton-Merten Syndrome 2

Alternate Names

SGMRT2

Defective Genes

DDX58

Clinical Characteristics

Ocular Features

Glaucoma has been diagnosed in multiple members of 4 a generation Korean family in which various features of this disorder were found.  The glaucoma is likely congenital in origin as it has been diagnosed in patients as young as 3 years of age

Systemic Features

Calcification of the aorta and other large vessels may be identified in childhood.  The aortic valve and coronary arteries may become calcified in young adults as well, sometimes resulting in aortic stenosis.  Arthritis resulting from calcified tendons as well as ligaments of the interphalangeal and metacarpophalangeal joints may occur in young adults.  The skin is often scaly and dry with psoriatic lesions.  The terminal tufts of the digits have evidence of erosion.

Genetics

Inheritance

Heterozygous mutations in the DDX58 gene (9p21.1) have been associated with this disorder.  Some of the clinical features overlap those of Singleton-Merten Syndrome 2 (182250) but this is a unique disorder caused by a different mutation (IFIH1).

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Treatment & Management

Glaucoma should be treated with pressure-lowering drugs and surgery.  It may be possible to decalcify cardiovascular structures in select patients and to perform valve replacement.

Selected Resources

Web Resources

Publications

Displaying 1 - 1 of 1

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

PubMedID: 25620203