aortic calcification

Singleton-Merten Syndrome 1

Clinical Characteristics
Ocular Features: 

Several children have been diagnosed with glaucoma in early childhood or during puberty.  Glaucoma surgery has been beneficial in some but visual damage may be severe.

Systemic Features: 

Patients have early-onset calcifications of the aorta and of the aortic and mitral valves which may be seen in childhood and can be responsible for heart failure and early death.  Osteoporosis of the limbs and widened medullary cavities have been seen.  Abnormal bone mineralization and extends to the jaws leading to tooth loss and early-onset periodontal disease.  Eruption of both primary and permanent teeth is delayed but tooth roots can be truncated as well.  The hips dislocate easily due to shallow acetabulae and patients are susceptible to tendon tears.

Hypotonia and generalized weakness may be present which is sometimes exacerbated following a febrile illness.  The skin may be dry and scaly consistent with psoriasis and there may be photosensitivity.

The forehead is broad and prominent and the hairline is high and anterior.  The philtrum is smooth and the upper vermilion is thin.


Heterozygous mutations in the IFIH1 gene (2q24.2) are responsible for this disorder.  Another form of Singleton-Merten Syndrome (SGMRT2; 609631) is the result of mutations in the DDX58 gene. 

Autosomal dominant
Treatment Options: 

Treatment is directed at specific problems such as fractures, glaucoma, and periodontal disease.

Article Title: 

A specific IFIH1 gain-of-function mutation causes 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. A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome. Am J Hum Genet. 2015 Feb 5;96(2):275-82.

PubMed ID: 
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